FIELD OF THE INVENTION:
The present invention relates to an improved process for preparing Napropamide - M.
BACKGROUND AND PRIOR ART:
N,N-diethyl-2-(a-naphthoxy)propionamide is known as napropamide, and is generally
marketed under the trade name "Devrinol". It is used for pre-emergence control of
annual grasses and broad-leaved weeds in many crops and plantations.
The second carbon atom at the propionamide group in napropamide has a hydrogen
atom, a methyl group, a naphthoxy moiety and a carboxamide group thereby forming a
chiral center. Hence the molecule [Fig I] can exist in two chiral stereoisomers: D or (R)
and L or (S)-isomers.

Various processes reported in the literature for the synthesis of this compound
generally result in producing a mixture of these isomers, usually racemic mixtures and
they are difficult to resolve.
US3718455 discloses a process for the preparation of D- and L-isomers of
Napropramide in Example No. 7. The example discloses that dl-(2-a-
naphthoxy)propionic acid was reacted with cinchonine (naturally occurring optically
active base) to obtain diastereomeric salt of cinchonine with dl-(2-a-
naphthoxy)propionic acid. Theses salts were resolved into d- and l-isomer through
preferential crystallization technique. The d-acid was regenerated from the d-isomeric
salt, and was further treated with phosgene in the presence of DMF to obtain acid
chloride. This acid chloride was then treated with diethyl amine in the presence of

triethylamine to obtain a crude product in the form of oil (indicating inferior purity). This
crude material was crystallized to get desired isomer of Napropamide. The above
process does not involve reaction at chiral centre, but uses classical and conventional
method of obtaining a stereo isomer by way of resolution of a racemic compound.
However, the resolution procedure for preparing Napropamide-M is quite cumbersome
and results into a low yield of the target product. The complex resolution technique and
the low yield renders this process industrially unviable for a large scale manufacture of
Napropamide-M.
WO2009004642 relates to a process for manufacturing high purity D-(-)-N,N-diethyl-2-
(a -naphthoxy)propionamide. The disclosed process is carried out in presence of an
aqueous alkali metal hydroxide. The three-step process resulted in N,N-diethyl-2-(a-
naphthoxy) propionamide having an overall yield of 83% with 84% of R-isomer.
Upgradation of this product to R-isomer having 97% purity is achieved by repeated
crystallization procedures which are both tedious and uneconomical. This aqueous
process also generates large quantities of aqueous waste, which is required to be
treated with expensive purification techniques before being discharged.
It is thus concluded that the prior art processes are carried out in an aqueous medium
or in the presence of the aqueous base.
OBJECT OF THE INVENTION:
The present invention described hereinafter achieves at least one, and preferably but
not necessarily, all of the advantages mentioned below.
It is one object of this invention to provide a process for preparation of R-(-)-N,N-
diethyl-2-(a-naphthoxy) propionamide.
A further object of the present invention is to provide a process for preparation of R-(-)-
N,N-diethyl-2-(a-naphthoxy) propionamide in high yields.
A further object of the present invention is to provide a process for preparation of R-(-)-
N,N-diethyl-2-(a-naphthoxy) propionamide having high optical purity.

Yet another object of the present invention is to provide an environmentally friendly
process for preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy) propionamide.
SUMMARY OF THE INVENTION:
Therefore, in one aspect, the present invention provides a process for the preparation
of R(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I:

said process comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula II with
1-naphthoxide in the absence of water;

wherein X is a halo substituent selected from F, CI, Br and I.
In yet another aspect, the present invention provides the compound R-(-)- N,N-diethyl-
2-(a-naphthoxy)propionamide prepared via the intermediate (L)-N,N-diethyl-2-
halopropionamide in the absence of water.
DETAILED DESCRIPTION OF THE INVENTION
It has been found by the present inventors .that it is possible to achieve the preparation
of Napropamide-M in substantially high yield as well as high chemical and chiral purity
when the reaction is carried out in the absence of water.

Therefore, in one aspect, the present invention provides a process for the preparation
of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I:

said process comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula II with
1-naphthol in the absence of water;

wherein X is a halo substituent selected from F, CI, Br and I.
The present invention also provides the compound R-(-)- N,N-diethyl-2-(a-
naphthoxy)propionamide prepared via the intermediate (L)-N,N-diethyl-2-
halopropionamide in the absence of water.
It has been found that the preparation of D-(-)-N,N-diethyl-2-(a-
naphthoxy)propionamide can be carried out in substantially high yield as well as high
chemical and chiral purity via the intermediate (L)-N,N-diethyl-2-halopropionamide
when such process is carried out in the absence of water.
Therefore, in an aspect, the present invention provides a process for the preparation of
R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I:


said process comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula II with
1-naphthol in the absence of water:

wherein X is a halo substituent selected from F, CI, Br and I.
In an embodiment, the precise manner of reacting the compound of formula II with 1-
naphthol in the absence of water is not particularly limiting and may be carried out
according to the present invention in a plurality of ways, all of which form alternate
embodiments of the present invention. Moreover, the selection of one of said plurality
of manners of eliminating water during the reaction of the compound of formula II with
1-naphthol does not preclude eliminating water concurrently through any other manner
contemplated according to the present invention.
In one embodiment, carrying out the reaction between the compound of formula II and
1-naphthol in the absence of water is achieved by using a non-aqueous base.
Thus, in this embodiment, the present invention provides a process for the preparation
of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said process
comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula II with 1-naphthol in
the presence of a non-aqueous base.
In this embodiment, the substituent X in the compound of formula II is a halo
substituent selected from F, CI, Br and I.

In an embodiment, the non-aqueous base may be a non-aqueous organic base or a
non-aqueous inorganic base.
In one embodiment, the non-aqueous organic base may be selected from alkylamines,
alkanolamines, pyridine, picolin, quinolin and N,N-dialkyl anilines. In an embodiment,
the alkanolamines may be selected from monoethanolamine, diethanolamine and
triethanolamine.
In another embodiment, the alkylamines may be selected from primary alkylamines,
secondary alkylamines or tertiary alkylamines.
In yet another embodiment, the alkylamines may be selected from, but not limited to,
propylamine, 2-propylamine, methylamine, dimethylamine, trimethylamine,
triethylamine, tripropylamine and tri.n-butylamine.
In another embodiment, the non-aqueous base is a non-aqueous inorganic base
selected from alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal
carbonates, alkaline earth metal carbonates and alkali metal alkoxides.
In this embodiment, the alkali metal hydroxide may be selected from hydroxides of
sodium and potassium, although hydroxides of other alkali metals are not excluded.
In another embodiment, the alkaline earth metal hydroxide may be selected from
hydroxides of magnesium and calcium, although hydroxides of other alkaline earth
metals are not hereby excluded.
In another embodiment, the alkali metal carbonate may be selected from carbonates of
sodium or potassium, although carbonates of other alkali metals are not excluded.
In another embodiment, the alkaline earth metal carbonate may be selected from
carbonates of magnesium and calcium, although the carbonates of other alkaline earth
metals are not hereby excluded.
In yet another embodiment, the alkali metal alkoxides may be selected from alkoxides
of sodium and potassium although alkoxides of other alkali metals are not excluded.
In this embodiment, the term "alkoxide" includes references to the conjugate base of an
alcohol, the organic moieties of which may be substituted or unsubstituted.

In an embodiment, the alkoxide may be the conjugate base of an alcohol comprising an
organic chain bound to a negatively charged oxygen atom and may be selected from
the formula RO--, wherein R is C1-C6 carbon chain, which may be unsubstituted or
substituted at any position.
In yet another preferred embodiment, the non-aqueous inorganic base including alkali
metal hydroxides is alternatively selected from lithium hydroxide, sodium hydroxide,
and potassium hydroxide; alkaline earth metal hydroxides selected from calcium
hydroxide and barium hydroxide; ammonium hydroxide; alkali metal carbonates
selected from lithium carbonate, sodium carbonate, and potassium carbonate; alkaline
earth metal carbonate selected from calcium carbonate and barium carbonate; alkaline
earth metal oxide selected from calcium oxide and barium oxide; and alkali metal
alkoxide selected from sodium methoxide, sodium ethoxide, sodium isopropoxide and
potassium tertiary butoxide.
Thus, in another embodiment, the present invention provides a process for the
preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said
process comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula II with 1-
naphthol in the presence of a non-aqueous organic base or a non-aqueous inorganic
base.
In this embodiment, the substituent X in the compound of formula II is a halo
substituent selected from F, CI, Br and I.
In a preferred embodiment, the non-aqueous inorganic base may be selected from
sodium hydroxide or potassium hydroxide.
Thus, in this embodiment, the present invention provides a process for the preparation
of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said process
comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula II with 1-naphthol in
the presence of non-aqueous sodium hydroxide or potassium hydroxide.
In this embodiment, the substituent X in the compound of formula II is a halo
substituent selected from F, CI, Br and I.
In yet another preferred embodiment, the term "non-aqueous sodium hydroxide"
includes references to sodium hydroxide flakes.

In an aspect, carrying out the reaction between the compound of formula II and 1-
naphthol in the absence of water is achieved, in part, by using anhydrous compound of
formula II and anhydrous 1-naphthol, in addition to use of a non-aqueous base.
Therefore, in this aspect, the present invention provides a process for the preparation
of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said process
comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula II with 1-naphthol in
the presence of a non-aqueous base, wherein said compound of formula II and 1-
naphthol are anhydrous.
In this embodiment, the substituent X in the compound of formula II is a halo
substituent selected from F, CI, Br and I.
The term anhydrous in relation to the compounds of formula II and 1-naphthol shall
include references to the compounds comprising less than 2 %, preferably less than 1
% of dissolved water.
In a preferred embodiment, the preferred halo substituent is chloro.
Therefore, in this embodiment, the present invention provides a process for the
preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said
process comprising reacting (L)-N,N-diethyl-2-chloropropionamide of formula ll(A)

with 1-naphthol in the presence of a non-aqueous base.
In a preferred embodiment, 1-naphthol may be deprotonated in the presence of a non-
aqueous base described above to anhydrous alkali or alkaline earth 1-naphthoxide,
which may be subsequently reacted with a compound of formula II, preferably with the
compound of formula ll(A), to prepare the compound of formula I.
Therefore, in this embodiment, the present invention provides a process for the
preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said
process comprising:

(a) deprotonating anhydrous 1-naphthol in the presence of a non-aqueous base
described above to prepare anhydrous alkali or alkaline earth 1-naphthoxide;
and
(b) reacting (L)-N,N-diethyl-2-chloropropionamide of formula ll(A) or (L)-N,N-
diethyl-2-halopropionamide of formula II with anhydrous alkali or alkaline earth
1-naphthoxide.

In this embodiment, the alkali or alkaline earth moiety of the anhydrous alkali or
alkaline earth 1-naphthoxide is derived from the alkaline or alkaline earth moiety of the
non-aqueous base.
In an embodiment, the process of the present invention is carried out in an organic
solvent, the organic solvent being selected from but not limited to hydrocarbon
solvents; ether solvents selected from diethyl ether, tetrahydrofuran, 1, 4-dioxane, 1-
butyl methyl ether, dimethoxyethane, diphenyl ether, and ethylene glycol, dimethyl
ether; aprotic polar solvents selected from acetone, methyl isobutyl ketone, methyl
ethyl ketone, dimethyl formamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide and
dimethyl acetamide; halogenated hydrocarbons selected from methylene chloride,
chloroform, ethylene dichloride, trichloroethylene, and chlorobenzene; nitrogen
containing solvents selected from acetonitrile, dimethylformamide, dimethylacetamide,
diethylacetamide, dimethylbutyramide, N-methyl-2-pyrrolidone; and heteroaromatic
solvents selected from pyridine and picoline.
In another embodiment, the organic solvent may be selected from aliphatic
hydrocarbon solvents and aromatic hydrocarbon solvents. Aliphatic hydrocarbon
solvents may be selected from, but not limited to, solvents such as hexane, heptane,
cyclohexane, methyl cyclohexane. Aromatic hydrocarbon solvents may be selected
from but not limited to solvents such as benzene, toluene, and xylene.

In a preferred embodiment, the process of the present invention is carried out in the
presence of toluene.
In yet another embodiment, the precise manner of carrying out the reaction between
the compound of formula II, or preferably compound 11(A), with 1-napththol or alkali or
alkaline earth 1-naphthoxide is not particularly limiting and may be carried out
conventionally by a skilled organic chemist.
Exemplarily, in one embodiment, 1-napththol may be dissolved in the selected solvent,
to which a required quantity of a non-aqueous base may be added. The mixture may
be stirred at a first predetermined temperature. A solution including the compound of
formula II, or preferably the compound of formula ll(A), may then be added to the
mixture. The resulting mixture may then be stirred at a second predetermined
temperature for a first predetermined amount of time. The reaction mixture may then be
cooled to a third predetermined temperature and diluted with solvent and water.
In an embodiment, care should be taken to introduce water only subsequent to the
completion of the reaction. The organic and the aqueous layers may then be
separated. The solvent may be evaporated from the organic layer to leave behind the
pure target compound of formula I in a high yield and having a high chemical and
optical purity.
In an embodiment, the first predetermined temperature is selected between 50°C to
65°C, preferably between 55°C - 57°C.
In another embodiment, the second predetermined temperature is selected between
70°C to 95°C, preferably between 80°C - 85°C.
In an embodiment, the first predetermined amount of time may be selected between 6
hours to 10 hours, preferably about, 7 hours.
In another embodiment, the third predetermined temperature is selected between 40°C
to 60°C, preferably about 50°C.
In an embodiment, the reaction between the compound II or ll(A) with 1-naphthol or
alkali or alkaline earth 1-napththoxide was determined to be completed when the
percentage content of such compound II or ll(A) with 1-naphthol or alkali or alkaline

earth 1 -napththoxide was determined to be less than 0.5% by weight determined by
gas chromatography.
It was surprisingly found that the process of the present invention led exclusively to the
preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide having less than 5% of
the S-isomer, preferably less than 3% and more preferably less than 0.5% of the S-
isomer of N,N-diethyl-2-(a-naphthoxy)propionamide.
Thus, in yet another aspect, the present invention provides the compound R-(-)- N,N-
diethyl-2-(a-naphthoxy)propionamide prepared in the absence of water, and preferably
having less than 5% of the S-isomer, preferably less than 3% and more preferably less
than 0.5% of the S-isomer of N,N-diethyl-2-(a-naphthoxy)propionamide.
In yet another aspect, the present invention provides the compound R-(-)- N,N-diethyl-
2-(a-naphthoxy)propionamide substantially free of water. The term substantially free of
water is intended herein to denote that the inherent water content in the compound R-(-
)- N,N-diethyl-2-(a-naphthoxy)propionamide prepared according to the present
invention is less than 0.5%, preferably less than 1% and more preferably less than 3%
by weight.
This compound may be co-formulated with conventionally used agrochemical
adjuvants to prepare a composition comprising such R-(-)- N,N-diethyl-2-(a-
naphthoxy)propionamide. Thus, in this embodiment, the present invention provides a
composition comprising the compound R-(-)- N,N-diethyl-2-(α-naphthoxy)propionamide
prepared in the absence of water, and preferably having less than 5% of the S-isomer,
preferably less than 3% and more preferably less than 0.5% of the S-isomer of N,N-
diethyl-2-(a-naphthoxy)propionamide; and at least one agrochemically acceptable
adjuvant.
Accordingly, in another embodiment, the present invention also provides a process
comprising:
(a) reacting (L)-N,N-diethyl-2-halopropionamide of formula II with 1-naphthol in the
presence of a non-aqueous base, to prepare the compound R-(-)- N,N-diethyl-
2-(a-naphthoxy)propionamide prepared in the absence of water, and preferably
having less than 5% of the S-isomer, preferably less than 3% and more

preferably less than 0.5% of the S-isomer of N,N-diethyl-2-(α-
naphthoxy)propionamide; and
(b) preparing an agrochemical composition comprising said R-(-)- N,N-diethyl-2-(a-
naphthoxy)propionamide.
Therefore, the target compound of formula I prepared by the present process was
capable of being directly packed for commerce or co-formulated with suitable
excipients without requiring any intermediate isolation and purification step.
In an embodiment, the compound of formula II, or more preferably the compound of
formula 11(A), may be prepared by amination of a compound of formula III in the
absence of water. It has been found by the present inventors that it is possible to
achieve the preparation of compound II, more preferably compound 11(A), in
substantially high yield as well as high chemical and chiral purity when the reaction is
carried out in the absence of water. In an embodiment, the absence of water is
achieved by carrying out the reaction step in the presence of a non-aqueous base.
Therefore, in a second aspect, the present invention provides a process for the
preparation of a compound of formula II:

by reacting (L)-2-halopropionyl halide of formula III with diethylamine in the presence of
a non-aqueous base:

wherein X and X1, both same or different, are independently selected from F, CI, Br and
I.

In an embodiment, X and X1 are both chloro substituents.
Therefore, in this embodiment, the present invention provides a process for the
preparation of a compound of formula 11(A):

by reacting (L)-2-chloropropionyl chloride of formula lll(A):

with diethylamine in the presence of a non-aqueous base.
In an embodiment, the reaction between compound III, or more preferably 111(A), with
diethylamine may be carried out in the presence of a non-aqueous base, preferably or
alternately may be carried out using anhydrous compound of formula III or lll(A) and
diethylamine.
In an embodiment, the amination step is preferably carried out in the presence of a
solvent. In this embodiment, the solvent is selected from the list of solvents provided in
the description of the previous aspect of the invention.
In an embodiment, the amination step is carried out in hexane.
In an embodiment, the precise method of carrying out the reaction between the
compound of formula III or formula lll(A) and diethylamine and subsequent reaction of
compound II or 11(A) with 1-napthol or 1-napthoxide is not particularly limiting and may
be carried out conventionally by a skilled organic chemist.
Exemplarily, diethylamine, non-aqueous base and a solvent may be admixed and
stirred and cooled to a fourth predetermined temperature. The compound III or lll(A)

may be added slowly while maintaining the temperature below a fifth predetermined
temperature. After a second predetermined amount of time, the solid salt may be
filtered off, washed and concentrated.
In an embodiment, the fourth predetermined temperature is not limiting but may be
preferably selected between 0°C - 5°C.
In an embodiment, the fifth predetermined temperature is not limiting but may be
preferably selected below 5°C.
In an embodiment, the second predetermined amount of time is not limiting but may be
selected about 2.5 hours to about 5.5 hours.
In an aspect, the compound of formula II prepared by this amination step is employed
as the starting material for the preparation of the target compound of formula I.
Therefore, in this aspect, the present invention provides a process for the preparation
of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said process
comprising:
(a) reacting (L)-2-halopropionyl halide of formula III with diethylamine in the
presence of an non-aqueous base to prepare a compound of formula II; and
(b) reacting (L)-N,N-diethyl-2-halopropionamide of formula II with 1-naphthol in the
presence of an non-aqueous base.
In an embodiment, the preferred halo substituent on the compounds of formula III or II
is chloro.
In a preferred embodiment, 1-naphthol may be deprotonated in the presence of a non-
aqueous base described above to anhydrous alkali or alkaline earth 1-naphthoxide,
which may be subsequently reacted with a compound of formula II, preferably with the
compound of formula ll(A), to prepare the compound of formula I.
Therefore, in this aspect, the present invention provides a process for the preparation
of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said process
comprising:

(a) reacting (L)-2-halopropionyl halide of formula III with diethylamine in the
presence of a non-aqueous base to prepare a compound of formula II;
(b) deprotonating anhydrous 1-naphthol in the presence of a non-aqueous base to
prepare anhydrous alkali or alkaline earth 1-naphthoxide; and
(c) reacting (L)-N,N-diethyl-2-halopropionamide of formula II with anhydrous alkali
or alkaline earth 1-naphthoxide .
In an embodiment, the reaction between compound III, or more preferably lll(A), with
diethylamine and the reaction between the compound II or ll(A) with 1-naphthol or 1-
naphthoxide may be carried out in the presence of a non-aqueous base, or alternately
may be carried out using anhydrous compound of formula III or lll(A) and diethylamine.
In an embodiment, (L)-2-halopropionyl chloride, diethylamine and non- aqueous base
of the amination step are added in mole ratio of 1:1:1 to 1:3:1.5. This step is preferably
carried out at 0°C to 5°C for 1-6 hours.
Optionally the reaction mass may be concentrated before utilizing the compound of
formula II in the subsequent step for the preparation of compound I.
In an alternate embodiment, the process for the preparation of a compound of formula I
from a compound of formula III or lll(A) in the absence of water may be carried out
alternatively as a single-pot process.
Therefore, in this embodiment, the present invention provides a process for the
preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said
process comprising reacting (L)-2-halopropionyl halide of formula III with diethylamine
and 1-napththol or alkali or alkaline earth metal 1-naphthoxide in the presence of a
non-aqueous base.
In an embodiment, the reaction between compound III, or more preferably lll(A), with
diethylamine and 1-napthtol or 1-naphthoxide may be carried out in the presence of a
non-aqueous base, or alternately may be carried out using anhydrous compound of
formula III or lll(A) and diethylamine and 1-naphthol or 1-naphthoxide.
Exemplarily, in one embodiment, the compound of formula III or lll(A) is reacted with 1-
naphthol or 1-napthoxide in the presence of a non-aqueous base in an organic solvent.

In an embodiment, the precise method of carrying out the single-pot reaction between
the compound of formula III or formula 111(A), diethylamide and 1-naphthol or 1-
naphthoxide is not particularly limiting and may be carried out conventionally by a
skilled organic chemist.
In an embodiment (L)-2-halo-N,N-diethyl propionamide and said a-naphthol and the
non-aqueous base are added in mole ratio of 1:1:1 to 1:1.1:2 and the reaction is carried
out at temperature from 55°C to 85°C.
The compound of formula III used in this step of the reaction is prepared by
halogenating the compound (L)-2-(-)halopropionic acid.
In this aspect, the compound of formula III

is prepared by reacting a compound (L)-2-(-)halopropionic acid of formula IV

with a halogenating agent.
In an embodiment, X and X1, both same or different, are independently selected from
F, CI, Br and I.
In a preferred embodiment, both X and X1 are chloro substituents. In this embodiment,
the compound of formula IV is reacted with a chlorinating agent.
In an embodiment, the chlorinating agent is thionyl chloride, although other chlorinating
agents are not excluded.

In another embodiment, compound of formula IV is reacted with a halogenating agent
in the presence of a catalyst.
In an embodiment, the catalyst is a base.
In an embodiment, the base is selected from but not limited to an amide group-
containing compound or a quaternary ammonium halide.
In another embodiment, the amide group-containing compound is selected from but not
limited to, dimethylformamide, diethylformamide, diethylacetamide, dimethylacetamide,
tetramethylurea, tetraethylurea, N-methyl-2-pyrrolidone, and
hexamethylphosphorictriamide. In a preferred embodiment, the amide group containing
compound is selected from dimethylformamide, diethylformamide and N-methyl-2-
pyrrolidine.
In another embodiment, the quaternary ammonium halide is selected from but is not
limited to, tetramethyl ammonium chloride, tetraethylammonium chloride, tetra-n-
butylammonium chloride, bezyltrimethylammonium chloride, bezyltriethylammonium
chloride, benzyltri-n-butylammoniumchlroride, tetramethylammonium bromide,
tetraethylammonium bromide, tetra-n-butylammonium bromide,
benzyltrimethylammonium bromide and benzylth-n-butylammonium bromide.
The base may be used n an amount of about 0.01 to 0.5 mole per mole of acid.
In an embodiment said (L)-2-(-)halopropionic acid and said thionyl chloride are added
in a mole ratio of 1:1.05 to 1:2.5.
The reaction of this step is optionally carried out in presence of an organic solvent. The
said organic solvent is preferably an aprotic organic solvent. The aprotic solvent is
particularly not limited but includes, among others, aliphatic hydrocarbon solvents such
as n-hexane and methylcyclohexane, aromatic hydrocarbon solvents such as benzene,
toluene and xylene; ether solvents such as diethyl ether, tetrahydrofuran, 1, 4-dioxane,
1-butyl methyl ether, dimethoxyethane and ethylene glycol dimethyl ether; halogenated
hydrocarbon solvents such as methylene chloride, chloroform and 1,1,3-
trichloroethane; nitrogen-containing solvents such as acetonitrile, and
hexamethylphosphorictriamide. These may be used singly or two or more of them may
be used in combination.

The reaction of this step is carried out at temperature between -20°C to 120°C, more
preferably at 0°C to 80°C, most preferably at 20°C to 60°C.
In an embodiment, the compound of formula III is reacted with diethylamine to prepare
the compound of formula II, which is thereafter reacted with 1-naphthol or 1-
naphthoxide to prepare the target compound I.
Therefore, in another aspect, the present invention provides a process for the
preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said
process comprising:
(a) reacting a compound (L)-2-(-)halopropionic acid of formula IV

with a halogenating agent to obtain a compound of formula III

wherein X and X1, both same or different, are independently selected from F,
CI, Brand I;
(b) reacting (L)-2-halopropionyl halide of formula III with diethylamine in the
presence of a non-aqueous base to prepare a compound of formula II:


wherein X is a halo substituent selected from F, CI, Br and I;
(c) optionally deprotonating anhydrous 1-naphthol in the presence of a non-
aqueous base to prepare anhydrous alkali or alkaline earth 1-naphthoxide; and
(d) reacting (L)-N,N-diethyl-2-halopropionamide of formula II with 1-naphthol or 1-
naphthoxide in the presence of a non-aqueous base.
In an embodiment, the process steps (b), (c) and (d) may be carried out as a single-pot
process described in any of the embodiments above.
Thus, in this embodiment, the present invention provides a process for the preparation
of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I, said process
comprising:
(a) reacting a compound (L)-2-(-)halopropionic acid of formula IV with a
halogenating agent to obtain a compound of formula III

wherein X and X1, both same or different, are independently selected from F,
CI, Br and I; and
(b) reacting (L)-2-halopropionyl halide of formula III with diethylamine and 1-
napththol or alkali or alkaline earth metal 1-naphthoxide in the presence of a
non-aqueous base.
In an embodiment, the process step (b) may be carried out in the presence of a non-
aqueous base; or alternately may be carried out using anhydrous starting material
compound of formula IV or the reagents halogenating agent, diethylamine, 1-napththol
and the base. In this embodiment, the method of carrying out the reaction in the
absence of water is as described in any previous aspect or embodiment directed to
ensuring the absence of water from the reaction mixture.

The present inventors have further surprisingly found that the entire reaction scheme
could be carried out as single-pot process if the anhydrous condition i.e. absence of
water from the reaction system is maintained.
Therefore, in this embodiment, the present invention provides a process for the
preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide of the formula I:
Error! Reference source not found.
said process comprising:
(a) admixing diethylamine, a non-aqueous base, 1-naphthol in a solvent; and
(b) adding a compound (L)-2-(-)halopropionic acid of formula IV to the admixture of
step (a) in the absence of water.

For example, in one embodiment, a non-aqueous base as described in any one of the
preceding embodiments may be used.
In another embodiment, the compound of formula IV or the reagents diethylamine, acid
scavenger and 1-naphthol used may be anhydrous.
The one-pot non-aqueous process does not involve isolation and purification of the
intermediates or work up and water washings. Further due to elimination of water
washings, there is a reduction in effluents hence the process is environmental friendly.
In another preferred embodiment, the present invention provides a non-aqueous
process for preparing R-(-)-N,N-diethyl-2-(a-naphthoxy) propionamide comprising steps
of:

a) reacting (L)-2-(-)halopropionic acid with thionyl chloride and catalyst to form (U-
2-(+)-halopropinyl chloride;
The reaction of step (a) is carried out by slowly adding thionyl chloride to the
acid and the basic compound at particular reaction temperature and stirred for
several hours till the reaction is complete. Excess thionyl chloride and S02 and
HCI generated during the reaction are expelled out of the reaction mass either
by passing an inert gas such as nitrogen or by applying vacuum.
b) reacting the (L)-2- halopropionyl chloride with diethylamine in presence of non-
aqueous base to form (L)-2-(+)-halo-N,N-diethyl propionamide; and
The reaction of step (b) is carried out by mixing diethyl amine and non-aqueous
base in the solvent and cooled to 0°C. The acid chloride from step i) is added
while maintaining the temperature below 5°C. The reaction is monitored by GC.
After completion of the reaction, the reaction mass can be further taken to step
iii), or the reaction mass may be cooled to 50°C-55°C, and salt is filtered off.
c) reacting the mass containing (L)-2-halo-N,N-diethyl propionamide with metal a-
naphthoxide in presence of non- aqueous base to form R-(-)-N,N-diethyl-2-(a-
naphthoxy)propionamide.
The reaction mass of step (b), 1-naphthol and non-aqueous base are added at
55°C-60°C. After stirring at the same temperature, the reaction temperature is
raised to 82°C-85°C and stirred till 1-naphthol content is less than 0.5%. Water
formed during the reaction is removed azeotropically during the reaction and
the reaction mass is cooled to 50°C and salt is filtered off to obtain
Napropamide - M.
The following examples are presented to define the invention more fully without any
intention of being limited thereby. All percentages and ratios are by weight unless
otherwise specified.
EXAMPLES:

Example 1:
Preparation of compound I: R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(l)
To a-naphthol (1.01 mole) in toluene was added non-aqueous sodium hydroxide (2.2
mole) and stirred at 55-57°C. The solution of (L)-2-(+)-halo-N,N-diethyl propionamide
was added and stirred at 80-85°C for 7 hours. The reaction mixture was cooled to 50°C
and diluted with toluene and water. The layers were separated and solvent evaporated
from organic layer to get napropamide-M. Yield-97%, chemical purity-95%, optical
purity-93% of R-isomer.
Reference Example:
The toluene solution of (L)-2-(+)-halo-N,N-diethvl propionamide (3.95 mole) and a-
naphthol (3.59 mole) in toluene were stirred. Aq. NaOH (48% aq., 7.7 mole) solution
was added drop wise at 55-57°C. The reaction mixture was stirred at 95°C for 6-7
hours, the reaction was worked up to get light brown solid, m.p. 75-79°C. Yield-85%
based on acid chloride, chemical purity-94%, optical purity 84% R-isomer and 16% S-
isomer.
Example 2:
Preparation of compound R-(-)-N,N-diethyl-2-(a-naphthoxv)propionamide.(l) from
compound (L)-2-(+)-halo-N,N-diethyl propionamide II:
Preparation of (L)-2-(+)-halo-N.N-diethvl propionamide (II) (L-CIPAM)
Mixture of Diethylamine (DEA) (1.1. mole), NaOH (1.2 mole) flakes, and hydrocarbon
solvent (hexane) were stirred and cooled to 0-5°C. L-2-Chloropropionyl chloride(CPC)
(1.0 mole) was added slowly while maintaining the temp below 5°C. After 3 hours, the
solid salt was filtered off, washed with the solvent, the filtrates were mixed and
concentrated. L-CIPAM analysis - Yield-94%, chemical purity -93.2%, optical purity-
95.2% L-isomer
Preparation of Napropamide - M
To a-naphthol (1.01 mole) in solvent was added non-aqueous sodium hydroxide (2.2
mole) and stirred at 55-57°C. The amide solution of (L)-2-(+)-halo-N,N-diethvl

propionamide (II) was added and stirred at 80-85°C for 7 hours. The reaction mixture
was cooled to 50°C and diluted with solvent and water. The layers were separated and
solvent evaporated from organic layer to get napropamide-M. Yield -97%, chemical
purity -95%, optical purity -93% R-isomer.
Example 3:
Preparation of R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(I) from (L)-2-(+)-halo-
N.N-diethyl propionamide (II):
Preparation of amide (L)-2-(+)-halo-N,N-diethyl propionamide (II) (L-CIPAM): A Mixture
of DEA (2.1 mole), and hydrocarbon solvent (hexane) were stirred and cooled to 0-5°C.
L-2-Chloropropionyl chloride (1.0 mole) was added slowly while maintaining the temp
below 5°C. After 5 hours, the solid salt was filtered off, washed with the solvent, the
filtrates were mixed and concentrated to get L-CIPAM; analysis - Yield-86%, chemical
purity -86.7, optical purity-93.21%L-isomer.
Preparation of compound R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(l): To a-
naphthol (1.01 mole) in solvent toluene was added non-aqueous sodium hydroxide (2.2
mole) and stirred at 55-57°C. The amide solution of (L)-2-(+)-halo-N,N-diethyl
propionamide (II) in toluene was added and stirred at 80-85°C for 7 hours. The
reaction mixture was cooled to 50°C and diluted with solvent and water. The layers
were separated and solvent evaporated from organic layer to get napropamide - M;
Yield-97%, chemical purity-95%, optical purity-93% R-isomer.
Example 4:
Preparation of compound R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(l)
Preparation of amide (L)-2-(+)-halo-N,N-diethyl propionamide (II) (L-CIPAM): Mixture of
Diethylamine (DEA) (1.2 mole), Na2C03 (1.0 mole), and hydrocarbon solvent (hexane)
were stirred and cooled to 0-5°C. L-2-Chloropropionyl chloride (1.0 mole) was added
slowly while maintaining the temp below 5°C. After 3.5 hours, the solid salt was filtered
off, washed with the solvent, the filtrates were mixed and concentratedto get L-CIPAM;
analysis - Yield-94%, chemical purity -93.2%, optical purity-94.9% L-isomer.
Preparation of compound R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(l)

: To a-naphthol (1.01 mole) in solvent was added non-aqueous sodium hydroxide (2.2
mole) and stirred at 55-57°C. The amide solution of (L)-2-(+)-halo-N,N-diethvl
propionamide (II) was added and stirred at 80-85°C for 7 hours. The reaction mixture
was cooled to 50°C and diluted with solvent and water. The layers were separated and
solvent evaporated from organic layer to get napropamide - M;. Yield-97%, chemical
purity-95%, optical purity-93% R-isomer.
Example 5:
Preparation of compound R-(-)-N,N-diethyl-2-(a-naphthoxv)propionamide.(l) from L-2-
chloropropionic acid
Preparation of compound L-2-Chloropropionyl chloride(lll) from L-2-chloropropionic
acid(IV): L-2-chloropropionic acid (1.0 mole), catalyst (DMF) (2% by wt.), were stirred
at 55°C and SOCI2(1.2 mole) was added. After 7 hours, the gases (S02 and HCI) and
excess SOCI2 were expelled out to get the acid chloride III; Yield-97.8%, optical purity-
96.76 L-isomer, 3.24% D-isomer.
Preparation of Compound (L)-2-(+)-halo-N,N-diethyl propionamide (ll)(L-CIPAM) :
Mixture of Diethylamine (2mole), and hydrocarbon solvent (toluene) were stirred and
cooled to 0-5°C. L2-Chloropropionyl chloide (1mole) was added slowly while
maintaining the temp below 5°C. After 5 hours, the solid salt was filtered off, washed
with the solvent, the filtrates were mixed and concentrated to 2/3rd to get CIPAM
solution . L-CIPAM analysis on solvent free basis - chemical purity -97%, optical purity
-95.76% L-CIPAM, 4.24% D-isomer.
Example 6:
Preparation of compound L-2-Chloropropionyl chloride from L-2-chloropropionic acid:
Preparation of acid chloride L-2-Chloropropionyl chloride: The acid L-2-Chloropropionic
acid (1.0 mole), catalyst (DMF, DEF or NMP) (2% by wt.), were stirred at 55°C and
SOCI2 (1.2 mole) was added. After 7 hours, the gases (SO2 and HCI) and excess
SOCI2 were expelled out to get the acid chloride. Yield-98% by wt., chemical purity-
98%, optical purity- 96-97% L-isomer.
Example 7

One pot preparation of R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(l) from L-2-
Chloropropionyl chloride:
A Mixture of DEA (1.1 mole), and NaOH flakes (1.2 mole) in toluene (151 ml) were
stirred and cooled to 5°C. L-2-chloropropionyl chloride (CPC) (1.1 mole) was added
slowly while maintaining the temperature below 5°C. After 3 hours, an aliquot was
withdrawn and analyzed for completion of reaction. The analysis showed L-CIPAM -
94.38%, and no L-CPC. The reaction temperature was raised to 55°C and a-naphthol
(1.1 mole) and NaOH flakes (2 moles) were added and stirred and 55°C for 1 hour. The
reaction temperature was raised to 83-85°C while removing the water azeotropically.
After 7 hours, L-CIPAM and a-naphthol were <0.5% by GC. The reaction mixture was
cooled to 55°C and salts were filtered off to get Napropamide-M; Yield-85%, chemical
purity -96%, optical purity - 96.26 R-isomer, 3.24% S-isomer.
Example 8:
Sequential preparation of compound R-(-)-N,N-diethyl-2-(a-naphthoxv)propionamide.(l)
from compound L-2-chloro - propionic acid
Preparation of acid chloride (L-2-chloropropionic acid ): The L-2-chloropropionicacid
(1.0 mole), catalyst (DMF, DEF or NMP) (2% by wt.), were stirred at 55°C and SOCI2
(1.2 mole) was added. After 7 hours, the gases (S02 and HCI) and excess SOCI2 are
expelled out to get the L-2-chloropropionic acid chloride. Yield-98% by wt., Chemical
Purity-98%, Optical Purity- 96-97% L-isomer.
Preparation of (L)-2+(+)-halo-N.N-diethyl propionamide (L-CIPAM): A Mixture of DEA
(1.1. mole), NaOH (1.2 mole) flakes, and hydrocarbon solvent (hexane) were stirred
and cooled to 0-5°C. L-2- chloropropionyl chloride (1.0 mole) was added slowly while
maintaining the temp below 5°C. After 3 hours, the solid salt was filtered off, washed
with the solvent, the filtrates were mixed and concentrated. L-CIPAM Yield-94%,
Chemical Purity -93.2%, Optical Purity -95.2% L-isomer.
Preparation of compound R-(-)-N,N-diethvl-2-(α-naphthoxv)propionamide.(l): To α-
naphthol (1.01 mole) in solvent was added non-aqueous sodium hydroxide (2.2 mole)
and stirred at 55-57°C. The solution of (L)-2-(+)-halo-N,N-diethvl propionamide (L-
CIPAM) in toluene was added and stirred at 80-85°C for 7 hours. The reaction mixture
was cooled to 50°C and diluted with solvent and water. The layers were separated and

solvent evaporated from organic layer to get napropamide - M. Yield-97%, Chemical
Purity-95%, Optical Purity-93% R-isomer.
Example 9:
Sequential preparation of compound R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(l)
from L-2-chloropropionic acid
Preparation of L-2-chloropropionic acid chloride (L-CPC): The L-2-chloropropionic acid
(1.0 mole), catalyst (DMF, DEF or NMP) (2% by wt.), were stirred at 55°C and SOCI2
(1.2 mole) was added. After 7 hours, the gases (SO2 and HCI) and excess SOCI2 are
expelled out to get the acid chloride. Yield-98% by wt., Chemical Purity-98%, Optical
Purity- 96-97% L-isomer.
Preparation of (L)-2-(+)-chloro-N,N-diethyl propionamide (L-CIPAM): Mixture of Diethyl
amine (2.1 mole), and hydrocarbon solvent (hexane) were stirred and cooled to 0-5°C.
L- L-2-chloropropionic acid chloride (CPC) (1.0 mole) was added slowly while
maintaining the temp below 5°C. After 5 hours, the solid salt was filtered off, washed
with the solvent, the filtrates were mixed and concentrated. L-CIPAM analysis - Yield-
86%, Chemical Purity-86.7, Optical Purity -93.21 %L-isomer
Preparation of compound R-(-)-N,N-diethyl-2-(a-naphthoxv)propionamide.(l)l: To a-
naphthol (1.01 mole) in solvent was added non-aqueous sodium hydroxide (2.2 mole)
and stirred at 55-57°C. The amide solution of (L)-2-(+)-chloro-N,N-diethyl propionamide
(L-CIPAM) was added and stirred at 80-85°C for 7 hours. The reaction mixture was
cooled to 50°C and diluted with solvent and water. The layers were separated and
solvent evaporated from organic layer to get napropamide - M. Yield-97%, Chemical
Purity-95%, Optical Purity -93% D-isomer.
Example 10:
Preparation of R-(-)-N,N-diethyl-2-(a-naphthoxv)propionamide.(l) using Sodium
carbonate as base
Preparation of L- 2-chloropropionic acid chloride: The L-2-chloropropionic acid (1.0
mole), catalyst (DMF, DEF or NMP) (2% by wt.), were stirred at 55°C and SOCI2 (1.2
mole) was added. After 7 hours, the gases (SO2 and HCI) and excess SOCI2 are

expelled out to get the L-2-chloropropionicacid chloride. Yield-98% by wt., Chemical
Purity-98%, Optical Purity- 96-97% L-isomer.
Preparation of amide (L)-2-(+)-chloro-N,N-diethyl propionamide (L-CIPAM): Mixture of
Diethyl amine (1.2 mole), Na2CO3 (1.0 mole), and hydrocarbon solvent (hexane) were
stirred and cooled to 0-5°C. L-2-Chloropropionyl chloride (1.0 mole) was added slowly
while maintaining the temp below 5°C. After 3.5 hours, the solid salt was filtered off,
washed with the solvent, the filtrates were mixed and concentrated to get L-CIPAM in
Yield-94%, Chemical Purity -93.2%, Optical Purity-94.9% L-isomer.
Preparation of compound R-(-)-N,N-diethvl-2-(a-naphthoxv)propionamide.(l): To a-
naphthol (1.01 mole) in solvent was added non-aqueous sodium hydroxide (2.2 mole)
and stirred at 55-57°C. The amide solution of (L)-2-(+)-chloro-N,N-diethvl propionamide
(L-CIPAM) was added and stirred at 80-85°C for 7 hours. The reaction mixture was
cooled to 50°C and diluted with solvent and water. The layers were separated and
solvent evaporated from organic layer to get napropamide - M. Yield-97%, Chemical
Purity-95%, Optical Purity-93% D-isomer.
Example 11:
Single-pot process for preparation of R-(-)-N,N-diethyl-2-(α-
naphthoxv)propionamide.(l):
A mixture of Diethylamine (1.1 mole), and NaOH flakes (2.2 mole), a-naphthol (1.1
mole) in toluene were stirred and cooled to 5°C. L-CPC (1.1 mole) was added slowly
while maintaining the temperature below 5°C. After 3 hours, an aliquot was withdrawn
and analyzed for completion of reaction. The analysis showed (L)-2-(+)-chloro-N,N-
diethyl propionamide (L-CIPAM) 94.38%, and no L-2-chloropropionyl chlorde. The
reaction temperature was gradually raised to 55°C, and stirred for 30 minutes. The
reaction temperature was raised to 83-85°C while removing the water azeotropically.
After 6 hours L-CIPAM and a-naphthol were <0.5% by GC. The reaction mixture was
cooled to 55°C and salts were filtered off. Napropamide -M: 88 .93 %; lmp:1 3.19 %, L-
CIPAM 0.34% and a-naphthol 4.51%
Optional crystallization of napropamide -M:
Taken crude R-(-)-N,N-diethvl-2-(α-naphthoxv)propionamide.(l) in a reaction kettle,
added 60:40 premix IPA:water solution with 50% product concentration (w/v).

Increased the temperature upto 64-65°C and maintained it at that temperature for 1
hour. Gradually cooled the reaction to room temperature and then to 4-5°C. Crystal
formation started at 35-37X. Filtered the solid at 4-5°C. Washed the wet cake with
IPA:water mixture and dried at 70°C for 3-4 hours till moisture was <0.5%. GC
analysis - by area 99%, Chemical Purity and Optical Purity - >95%.
In this specification and the accompanying claims the term "optically active compound"
is to be understood as meaning a compound which predominantly, or completely, by
weight, comprises one of the optical isomers of the compound. The term "optical purity"
of an optically active compound i.e. a compound consisting predominantly of one of the
two isomers, is to be understood as meaning the percentage by weight of the
preponderant isomer present in the compound. The term "optically active compound of
high optical purity" is to be understood as meaning a compound in which the
percentage by weight of the preponderant isomer is at least 90%.
The aforegoing reference has been made to components having known equivalents
and then such equivalents are herein incorporated as if individually set forth.
Accordingly, it will be appreciated that changes may be made to the above described
aspects and embodiments of the invention without departing from the principles taught
herein. Additional advantages of the present invention will become apparent for those
skilled in the art after considering the principles in particular form as discussed and
illustrated. Thus, it will be understood that the invention is not limited to the particular
embodiments described or illustrated, but is intended to cover all alterations or
modifications which are within the scope of the invention.

WE CLAIM:
1. A process for the preparation of R-(-)-N,N-diethyl-2-(a-naphthoxy)propionamide
of the formula I:

said process comprising reacting (L)-N,N-diethyl-2-halopropionamide of formula
II with 1-naphthol or 1-naphthoxide in the absence of water;

wherein X is a halo substituent selected from F, CI, Br and I.
2. The process as claimed in claim 1, wherein the reaction with 1-naphthol is
carried out in the presence of a non-aqueous base.
3. The process as claimed in claim 1 or claim 2, wherein the process is carried out
in the presence of a solvent selected from ether solvents selected from diethyl
ether, tetrahydrofuran, 1, 4-dioxane, 1-butyl methyl ether, dimethoxyethane,
diphenyl ether, and ethylene glycol, dimethyl ether; aprotic polar solvents
selected from acetone, methyl isobutyl ketone, methyl ethyl ketone, dimethyl
formamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide and dimethyl acetamide;
halogenated hydrocarbons selected from methylene chloride, chloroform,
ethylene dichloride, trichloroethylene, and chlorobenzene; nitrogen containing
solvents selected from acetonitrile, dimethylformamide, dimethylacetamide,
diethylacetamide, dimethylbutyramide, N-methyl-2-pyrrolidone; heteroaromatic

solvents selected from pyridine and picoline; and hydrocarbon solvents selected
from aliphatic hydrocarbon solvents and aromatic hydrocarbon solvents, said
aliphatic hydrocarbon solvents selected from hexane, heptane, cyclohexane,
methyl cyclohexane and said aromatic solvents selected from benzene,
toluene, and xylene.
4. The process as claimed in claim 3, wherein the solvent is toluene.
5. The process as claimed in any one of the preceding claims, wherein the
compound of formula II is prepared by reacting (L)-2-halopropionyl halide of
formula III with diethylamine in the absence of water:

wherein X and X1, both same or different, are independently selected from F,
CI, Br and I.
6. The process as claimed in any one of the preceding claims which is carried out
as a single-pot process comprising reacting (L)-2-halopropionyl halide of
formula III with diethylamine and 1-napththol or alkali or alkaline earth metal 1-
naphthoxide in a single-pot in the absence of water:

wherein X and X1, both same or different, are independently selected from F,
CI, Brand I.
7. The process as claimed in claim 5, wherein the compound of formula III is
prepared by reacting a compound (L)-2-(-)halopropionic acid of formula IV with
a halogenating agent.


8. The process as claimed in claim 7, which is carried out as a single pot process
comprising admixing diethylamine, a non-aqueous base, 1-naphthol in a
solvent; and adding a compound (L)-2-(-)halopropionic acid of formula IV to the
admixture in the absence of water:

9. The process as claimed in claims 1, 5, 6 and 8, wherein carrying out the
reactions in the absence of water comprises:
(a) reacting compound II with 1-naphthol or 1-naphthoxide, or compound III with
diethylamine, or compound III with diethylamine and 1-naphthol or 1-
naphthoxide, or compound IV with diethylamide and 1-napththol or 1-
naphthoxide in the presence of a non-aqueous base; or
(b) reacting anhydrous compound II with anhydrous 1-naphthol or anhydrous 1-
naphthoxide, or anhydrous compound III with anhydrous diethylamine, or
anhydrous compound III with anhydrous diethylamine and anhydrous 1-
naphthol or anhydrous 1-naphthoxide, or anhydrous compound IV with
anhydrous diethylamide and anhydrous 1-napththol or anhydrous 1-
naphthoxide.
10. The process as claimed in claim 9 comprising reacting compound II with 1-
naphthol or 1-naphthoxide, or compound III with diethylamine, or compound III
with diethylamine and 1-naphthol or 1-naphthoxide, or compound IV with

diethylamine and 1-napththol or 1-naphthoxide in the presence of a non-
aqueous base.
11. The process as claimed in any one of the preceding claims, wherein X or X1 is a
halo substituent selected from F, CI, Br and I.
12. The process as claimed in any one of the preceding claims, wherein the non-
aqueous base is selected from non-aqueous:

(a) alkanolamines selected from monoethanolamine, diethanolamine
and triethanolamine;
(b) pyridine;
(c) picolin;
(d) quinolin;
(e) N.N-DMA;
(f) N.N-DEA
(g) alkali metal hydroxide selected from hydroxides of lithium, sodium
and potassium;
(h) alkaline earth metal hydroxide selected from hydroxides of barium,
magnesium and calcium;
(i) alkali metal carbonate selected from carbonates of lithium, sodium or
potassium;
(j) alkaline earth metal carbonate selected from carbonates of barium,
magnesium and calcium;
(k) alkali metal alkoxides selected from alkoxides of lithium, sodium and
potassium, wherein the alkoxide is (a) the conjugate base of an
alcohol comprising an organic chain bound to a negatively charged
oxygen atom and may be selected from the formula RO-, wherein R
is C1-C6 carbon chain, which may unsubstituted or substituted at any
position;

(1) ammonium hydroxide;
(m) alkaline earth metal oxide selected from calcium oxide and barium
oxide;
(n) aralkylamines;
(o) aryl amines;
(p) aromatic amines;
(q) alkylamines selected from diethylamine, triethylamine, tributylamine,
ethyldiisopropylamine, and diemthylaniline;
(r) imidazole;
(s) lutidine; and
(t) N-methyl-2-pyrrolidone.
13. The process as claimed in claim 12, wherein the alkali metal alkoxide is
selected from sodium methoxide, sodium ethoxide, sodium isopropoxide and
potassium tertiary butoxide.
14. The process as claimed in any one of the preceding claims, wherein the non-
aqueous base is sodium hydroxide flakes or granules or prills.
15. The process as claimed in any one of the preceding claims additionally
comprising recrystallizing the compound of formula I from isopropanol-water
solution.
16. The process as claimed in any one of the preceding claims comprising a further
step of preparing an agrochemical composition comprising said compound of
formula VI.
17. The compound R-(-)- N,N-diethyl-2-(a-naphthoxy)propionamide prepared in the
absence of water, and preferably having less than 5% of the L-isomer,
preferably less than 3% and more preferably less than 0.5% of the S-isomer of
N,N-diethyl-2-(a-naphthoxy)propionamide.

18. A composition comprising the compound R-(-)- N,N-diethyl-2-(α-
naphthoxy)propionamide prepared in the absence of water, and preferably
having less than 5% of the S-isomer, preferably less than 3% and more
preferably less than 0.5% of the S-isomer of N,N-diethyl-2-(α-
naphthoxy)propionamide; and at least one agrochemically acceptable adjuvant.
19. The compound R-(-)- N,N-diethyl-2-(a-naphthoxy)propionamide substantially
free of water.
20. The compound as claimed in claim 18 comprising less than 3.0%, preferably
less than 1.5% and more preferably less than 0.5% by weight of water.

ABSTRACT

Disclosed herein is a non-aqueous process for preparing R-(-)-N,N-diethyl-2-(α-
naphthoxy) propionamide comprising steps of:
i. reacting (L)-2-(-)halopropionic acid with thionyl chloride and basic
compound to form (L)-2-(+)-halopropionyl chloride;
ii. reacting the (L)-2-halopropionyl chloride with N,N-diethylamine in
presence of non- aqueous base and an organic solvent to form (L)-2-(+)-
N,N-diethyl-halopropionamide; and
iii. reacting the mass containing (L)-2- N,N-diethyl-halopropionamide with
α-naphthol in the presence of a non- aqueous base to form R-(-)-N,N-
diethyl-2-(α-naphthoxy)propionamide.