Description:FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

“PROCESS FOR PREPARATION OF HALOGENATED ESTERS”
The present application is a modification to the process claimed in the complete specifications of the main application no IN202011002121 filed on 17.01.2020

SRF LIMITED, AN INDIAN COMPANY,
SECTOR 45, BLOCK-C, UNICREST BUILDING,
GURGAON – 122003,
HARYANA (INDIA)

The following specification particular describes the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention provides an improved process for the preparation of halogenated esters of formula I,

Formula I
wherein R1 is selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl; R is alkyl or halogenated alkyl group.

BACKGROUND OF THE INVENTION
The halogenated esters are very useful intermediates for preparation of complex organic molecules in the pharmaceutical or agricultural industries.
US Patent No. 4,332,815 describes a process for preparation of ethyl 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluoroheptanoate by reacting ethyl 3,3-dimethyl-4-pentenoate with 1,1,1-trichlorotrifluoroethane in t-butanol in presence of ethanolamine and cuprous chloride. The process is very exothermic and sudden increase in the heat of reaction pose safety concerns at commercial scale up. The exothermicity induces degradation and thereby reduces the yield and purity of the final product.
Indian Patent Application No. 202011002121 filed by the present applicant discloses a process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate by reacting methyl 3,3-dimethyl-4-pentenoate and ethanolamine in t-butanol with a solution of 1,1,1-trichloro-2,2,2-trifluoroethane in presence of copper chloride.
The inventor of the present invention now provides an alternate process for preparation of halogenated esters that is simple, economical, and commercially viable.

OBJECT OF THE INVENTION
The main object of present invention is to provide an alternate process for preparation of halogenated esters.

SUMMARY OF THE INVENTION
In an aspect of present invention provides an alternate process for preparation of halogenated ester of formula I,

Formula I
wherein R1 is selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl; R is alkyl, halogenated alkyl group,
comprising the steps of continuously feeding a homogeneous solution of a compound of formula II, a compound of formula III, an organic ligand in a polar solvent and copper carboxylate catalyst to a flow reactor,

Formula II
wherein R1 and R2 are defined as above,

Formula III
R is alkyl or halogenated alkyl group.
to obtain a compound of formula I.

DETAILED DESCRIPTION OF DRAWINGS
Figure 1 describes the reactor setup used in the preparation of the present invention.
As referred in figure 1, the flow reactor is equipped with entry mixers 1, circulating pump 2, heat exchanger 3, tube reactor 4, outlet coil 5 and product collection tank 6.
The compound of formula II, formula III, an organic ligand in a polar solvent and catalyst is fed to entry mixer 1. The homogeneous solution thus formed in the entry mixer 1 is continuously fed via pump 2, followed by heating under heat exchanger 3 into a tube reactor 4. The content of the tube reactor 4 is continuously discharged in product collection tank 6 through outlet coil 5.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, “copper carboxylate catalyst” is used as catalyst and may also be referred as catalyst in present specification.
The “copper carboxylate catalyst” refers to carboxylic acid salt of copper, wherein the carboxylic acid may contain alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, isopentyl, tertiary butyl, or the like; aryl such as phenyl, toluyl, halogenated alkyl such as trifluoromethyl, or the like.
The copper carboxylate catalyst is selected from a group consisting of copper acetate monohydrate, anhydrous copper acetate, copper propionate, copper hexanoate, copper 2-ethylhexanoate, copper trifluoroacetate, copper thiophene-2-carboxylate and copper benzoate or the like.
As used herein in Formula I, Formula II, and Formula III, R1 is selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl and R is an alkyl or halogenated alkyl group. The ‘halogen’ is selected from fluorine, chlorine, bromine, or iodine.
The ‘alkyl’ refers to C1-C3 alkyl group selected from methyl, ethyl or the like and ‘halogenated alkyl’ refers to C1-C3 substituted with any halogen such as fluorine, chlorine, bromine, or iodine and selected from dichlorotrifluoroethyl, chloroethyl, dichloroethyl, chloroethenyl, dichloroethenyl, trichloroethenyl, chloropropyl, chloropropenyl, chlorodifluoromethyl, trichloromethyl, trifluoromethyl, or the like.
The compound of formula III is selected from a group consisting of 1,1,1-trichloro-2,2,2-trifluoroethane, bromodichloromethane, dibromochloromethane, trichlorofluoromethane, dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, trichloroethylene (TCE), tetrachloroethylene (PCE), 1,2-dichloropropane, 1,3-dichloropropylene, dichlorodifluoromethane, tetrachloromethane, chlorotrifluoromethane, tribromochloromethane or the like.
As used herein, an “organic ligand” refers to organic ligands capable of forming a complex with the catalyst and capable of bringing the catalyst into solution. The organic ligand is an organic amine selected from a group consisting of ethanolamine, N,N,N',N'-tetramethylethylenediamine ethylamine, methylamine, n-propylamine, isopropyl amine, diethanolamine, propanolamine, pyridine tert-butylamine, n-butylamine, sec-butylamine, benzylamine, tri-n-butylamine, pyridine and combinations thereof.
In an embodiment of the present invention, the polar solvent involves alcohols, ethers and nitriles selected from a group consisting of ethanol, methanol, butanol, t-butanol, n-pentanol, iso-pentanol, t-pentanol, acetonitrile, and tetrahydrofuran or the like.
In an embodiment, the process of the present invention involve forming a homogeneous solution of compound of Formula II, compound of formula III, an organic ligand in a polar solvent and copper carboxylate catalyst.
In another embodiment, copper carboxylate catalyst may be used in anhydrous or hydrated form.
In preferred embodiment, catalyst is copper carboxylate catalyst and used in anhydrous form.
In another embodiment of the present invention, the homogeneous solution containing minimum amount of catalyst passes through the flow reactor. The less quantity of catalyst is helpful in reducing process cost, recycling operations and hazardous waste and makes process industrially more efficient.
In an embodiment of the present invention, the reaction is carried out in the continuous flow reactor.
In an embodiment of the present invention, a mole ratio of compound of formula III w.r.t compound of formula II is in the range of 1.0 to 1.5 mole equivalents.
In an embodiment of the present invention, a mole ratio of catalyst w.r.t compound of formula II is in the range of 0.005 to 0.10 mole equivalents.
In an embodiment of the present invention, a homogeneous solution is slowly fed into the reactor in a controlled manner at a resistance time of 35 minutes to maintain the heat of reaction between 100°C to 130°C.
In a preferred embodiment of the present invention, a homogeneous solution is fed through the coil to tube reactor with a resistance time of 35 minutes to maintain the heat of reaction between 100°C to 130°C.
It is observed that reaction is highly exothermic, the heat of the reaction generated is so high that it leads to run-away condition at plant scale. The present invention involves addition of raw materials in a controlled manner in order to control the heat of the reaction and ensure safety at commercial scale.
In a preferred embodiment of the present invention, the homogeneous solution contains 0.1 to 0.3% of catalyst.
The use of such minimal amount of reagent reduces the cost and the effluent load, thereby making it a cost effective and environment friendly option for large scale production.
In another embodiment of the present invention, the product is isolated by direct distillation and separation of product.
In another embodiment of the present invention, the organic solvent and the compound of formula III used in excess is recovered and recycled in the process.
In another embodiment of the present invention, the solvent used is recovered, recycled and reused.
In a particular embodiment, the present invention provides an alternate process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate using a continuous flow reactor comprising the steps of slowly and continuously adding of a homogeneous solution of methyl-3,3-dimethyl-4-pentenoate, 1,1,1-trichloro-2,2,2-trifluoro ethane, ethanolamine in t-butanol and copper acetate monohydrate into the reactor to obtain methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate, having purity 99%.
In an embodiment, the present invention provides an improved process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate via continuous flow reactor comprising the steps of slowly and continuously adding of a homogeneous solution of methyl-3,3-dimethyl-4-pentenoate, 1,1,1-trichloro-2,2,2-trifluoro ethane, ethanolamine in t-butanol and copper hexanoate into the reactor to obtain methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate.
In an embodiment, the present invention provides an improved process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate via continuous flow reactor comprising the steps of slowly and continuously adding of a homogeneous solution of methyl-3,3-dimethyl-4-pentenoate, 1,1,1-trichloro-2,2,2-trifluoro ethane, ethanolamine in t-butanol and copper 2-ethylhexanoate into the reactor to obtain methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate.
In the present invention, the solvent such as butanol and others are recovered and recycled and used for further batches.
The present invention for preparation of compound of formula I have following advantages over the known methods:
1. It provide high catalytic activity and reduces the number of operations at the industrial scale thereby making it cost effective.
2. The use of flow reactors prevents effluent load and improves yield significantly.
3. The mode of addition of reactant and reagent used in the reaction positively affects the product selectivity. The present inventors observed an improvement in the selectivity with slow and continuous addition of reagents to the reaction mixture.
4. The use of continuous flow reactor for the reaction to get 100% conversion, minimizes the impurity and thereby increases the selectivity towards the desired product significantly.
5. The process of present invention is safe at commercial scale.
6. The catalyst used by the present invention is highly soluble and thereby leads to the formation of homogeneous mixture.
7. The homogeneous mixture formed in the present invention gives higher reaction activity, selectivity, and overall ease in the reaction continuity.
8. The process of the present invention involves mild reaction conditions.
It has been found by the inventors that copper carboxylate is a better option compared to inorganic salts of copper.
The compound of Formula I is isolated by using techniques known in the art for example distillation, evaporation, column chromatography and layer separation or combination thereof.
The compound of Formula I so obtained by the present invention has a purity greater than 95 %, more preferably greater than 98 %, most preferably greater than 99.6 % by gas chromatography.
The compound of Formula I so obtained by the present invention has yield greater than 80%, more preferably greater than 85%, most preferably greater than 95% by gas chromatography.
Unless stated to the contrary, any of the words “comprising”, “comprises” and includes mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
The following example is given by way of illustration and therefore should not be construed to limit the scope of the present invention.

EXAMPLES
Example 1: Process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro- 3,3-dimethylheptanoate
Prepared a homogeneous solution (1) of methyl-3,3-dimethyl-4-pentenoate (100g), 1,1,1-trichloro-2,2,2-trifluoroethane (148.5g), t-butanol (102g), ethanolamine (1.26g) and copper acetate monohydrate (1.38g). The mixture (1) was fed through circulating pump (2) into a tube reactor (4) of 35mL volume with the feed rate of 1ml/min and resistance time of 35 minute at 10-12 bar pressure and temperature of 110°C for 3 hours and coil is heated by heat exchanger (3). The reaction mass was continuously discharged in the collection tank (6) through outlet coil (5). The reaction mass was distilled out under reduced pressure to recover excess 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol to recycle in the process and to obtained product. Purity: 99%; Yield: 95%
Example 2: Process for preparation of methyl-4,6,6,6-tetrachloro-3,3-dimethylhexanoate
Prepared a homogeneous solution (1) of methyl-3,3-dimethyl-4-pentenoate (100g), tetrachloromethane (121.9g), t-butanol (102g), ethanolamine (1.26g) and copper hexanoate (2.04g). The mixture (1) was fed through circulating pump (2) into a tube reactor (4) of 35mL volume with the feed rate of 1ml/min and resistance time of 35 minute at 10-12 bar pressure and temperature of 110°C for 3 hours and coil is heated by heat exchanger (3). The reaction mass was continuously discharged in the collection tank (6) through outlet coil (5). The reaction mass was distilled out under reduced pressure to recover excess tetrachloromethane and t-butanol to recycle in the process and to obtained product. Yield: 97% ; Purity: 99%
Example 3: Process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
Prepared a homogeneous solution (1) of methyl-3,3-dimethyl-4-pentenoate (100g), 1,1,1-trichloro-2,2,2-trifluoroethane (148.5g), t-butanol (102g), ethanolamine (1.26g) and copper hexanoate (2.04g). The mixture (1) was fed through circulating pump (2) into a tube reactor (4) of 35mL volume with the feed rate of 1ml/min and resistance time of 35 minute at 10-12 bar pressure and temperature of 110°C for 3 hours and coil is heated by heat exchanger (3). The reaction mass was continuously discharged in the collection tank (6) through outlet coil (5). The reaction mass was distilled out under reduced pressure to recover excess 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol to recycle in the process and to obtained product. Yield: 95%; Purity: 99%
Example 4: Process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
Prepared a homogeneous solution (1) of methyl-3,3-dimethyl-4-pentenoate (100g), 1,1,1-trichloro-2,2,2-trifluoroethane (148.5g), t-butanol (102g), ethanolamine (1.26g) and copper 2-ethylhexanoate (2.41g). The mixture (1) was fed through circulating pump (2) into a tube reactor (4) of 35mL volume with the feed rate of 1ml/min and resistance time of 35 minute at 10-12 bar pressure and temperature of 110°C for 3 hours and coil is heated by heat exchanger (3). The reaction mass was continuously discharged in the collection tank (6) through outlet coil (5). The reaction mass was distilled out under reduced pressure to recover excess 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol to recycle in the process and to obtained product. Yield: 95%; Purity: 99%
Example 5: Process for preparation of methyl-4,6,6,6-tetrachloro-3,3-dimethylhexanoate
Prepared a homogeneous solution (1) of methyl-3,3-dimethyl-4-pentenoate (100g), tetrachloromethane (121.9g), t-butanol (102g), ethanolamine (1.26g) and copper trifluoroacetate (2.0g). The mixture (1) was fed through circulating pump (2) into a tube reactor (4) of 35mL volume with the feed rate of 1ml/min and resistance time of 35 minute at 10-12 bar pressure and temperature of 110°C for 3 hours and coil is heated by heat exchanger (3). The reaction mass was continuously discharged in the collection tank (6) through outlet coil (5). The reaction mass was distilled out under reduced pressure to recover excess tetrachloromethane and t-butanol to recycle in the process and to obtained product. Yield: 97%; Purity: 99%
Example 6: Process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
Prepared a homogeneous solution (1) of methyl-3,3-dimethyl-4-pentenoate (100g), 1,1,1-trichloro-2,2,2-trifluoroethane (148.5g), t-butanol (102g), ethanolamine (1.26g) and copper trifluoroacetate (2.0g). The mixture (1) was fed through circulating pump (2) into a tube reactor (4) of 35mL volume with the feed rate of 1ml/min and resistance time of 35 minute at 10-12 bar pressure and temperature of 110°C for 3 hours and coil is heated by heat exchanger (3). The reaction mass was continuously discharged in the collection tank (6) through outlet coil (5). The reaction mass was distilled out under reduced pressure to recover excess 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol to recycle in the process and to obtained product. Yield: 95%; Purity: 99%
Example 7: Process for preparation of methyl-4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
Prepared a homogeneous solution (1) of methyl-3,3-dimethyl-4-pentenoate (100g), 1,1,1-trichloro-2,2,2-trifluoroethane (135g), t-butanol (102g), ethylamine (70% solution in water) (1.35g) and copper acetate monohydrate (1.38g). The mixture (1) was fed through circulating pump (2) into a tube reactor (4) of 35mL volume with the feed rate of 1ml/min and resistance time of 35 minute at 10-12 bar pressure and temperature of 110°C for 3 hours and coil is heated by heat exchanger (3). The reaction mass was continuously discharged in the collection tank (6) through outlet coil (5). The reaction mass was distilled out under reduced pressure to recover excess 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol to recycle in the process and to obtained product. Purity: 99%; Yield: 96%

WE CLAIM
1. An improved process for preparation of halogenated ester of formula I,

Formula I
wherein R1 is selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl; R is halogenated alkyl group,
comprising the steps of continuously feeding a homogeneous solution of a compound of formula II, a compound of formula III, an organic ligand in a polar solvent and copper carboxylate catalyst to a flow reactor,

Formula II
wherein R1 and R2 are defined as above,

Formula III
R is halogenated alkyl group.
to obtain a compound of formula I.
2. The process as claimed in claim 1, wherein the organic ligand is an organic amine selected from a group consisting of ethanolamine, N,N,N',N'-tetramethylethylenediamine ethylamine, methylamine, n-propylamine, isopropyl amine, diethanolamine, propanolamine, pyridine tert-butylamine, n-butylamine, sec-butylamine, benzylamine, tris n-butylamine, pyridine and combinations thereof.
3. The process as claimed in claim 1, wherein the polar solvent is selected from a from a group consisting of ethanol, methanol, butanol, t-butanol, n-pentanol, iso-pentanol, t-pentanol, acetonitrile, and tetrahydrofuran.
4. The process as claimed in claim 1, wherein the copper carboxylate catalyst is selected from copper acetate monohydrate, anhydrous copper acetate, copper propionate, copper hexanoate, copper 2-ethylhexanoate, copper trifluoroacetate, copper thiophene-2-carboxylate and copper benzoate.
5. The process as claimed in claim 4, wherein the copper carboxylate catalyst is used in the range from 0.1 to 0.3%.
6. The process as claimed in claim 1, wherein the reaction is carried out in the continuous flow reactor.
7. The process as claimed in claim 1, wherein the reaction is carried out at a temperature in the range from 100°C to 130°C.
8. The process as claimed in claim 1, wherein the compound of formula III is selected from a group consisting of 1,1,1-trichloro-2,2,2-trifluoroethane, bromodichloromethane, dibromochloromethane, trichlorofluoromethane, dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, trichloroethylene, tetrachloroethylene, 1,2-dichloropropane, 1,3-dichloropropylene.
9. The process as claimed in claim 1, wherein the process is as illustrated in the figure 1.

Dated this 17th February 2023.

SRF LIMITED NO. OF SHEETS: 01
APPLICATION NO. ………………. SHEET NO. 01

Figure 1: Continuous flow reactor
, Claims:NA