FIELD OF THE INVENTION:
The present invention relates to the process for the preparation of azidoalkylamine and its
salts
BACKGROUND OF THE INVENTION:
Azidoalkyl amines (Formula-1) are used as an intermediate in preparation of active pharmaceutical ingredients, poymer synthesis or more broadly is useful in organic synthesis. In J.Org.Chem. 1993,58,3736-3741,the synthesis of azidoalkylamines described which
involves reaction of 1 -chloro-4-ami no butane hydrochloride and sodium azide at 80°C for 15
hrs in the presence of diethylether solvent and KOH pellets. After separation of layers,
aqueous layer was extracted with diethylether to get oil product of 50% yield which further
purified by bulb to bulb distillation. The disadvantage of said process is lower yield of 50%.
In J.Org.Chem. 1957,22,238-240, the synthesis of alkyl azides starting from alkyl bromides
and iodides in alcohols or 2-alkoxyethanols with the addition of water is described.
In J. Am.Chem.Soc.,77,951 (1995) reported the formation of an azeotrope of butyl azide and
methanol and also point out that the combination of butyl bromide and sodium azide without
the use of solvent did not lead to the formation of butyl azide.
US 2008/0039613 Al discloses the process for the production of azidoalkylamines which
comprises reaction of a Afunctional alkane with two groups of different nucleofugicity and
azide in presence of polar solvent and by elimination of one nucleofugic group
monofunctional azido alkane is obtained which further reacted with an amine and with the
elimination of the second neuclofugic group azidoalkyl amine obtained which further purified
with chromatography as free base, as a salt with the acid released during the reaction in
second step or as a salt from the precipitation with an acid.
The above said process is lengthy and resulting in lower yield. Moreover purification with
chromatography is tedious, time consuming and inapplicable to industry level.
WO 2015181723 Al discloses different acid salts of 4-azidobutylamine such as
azidobutylamine cholate. 4-azidobutylamine p-toluenesulphonate, 4-azidobutylamine
camphorsulphonate, 4-azidobutylamine deoxycholate. 4-azidobutylamine L-dibenoyl tartrate

The synthesis of azidoalkylamines is difficult and results in poor yield and purity. The azidoalkylamines are difficult to handle as they are explosive in nature. Low molecular weight azides are explosive and should not be isolated in neat form nor should one attempt to purify them.
Hence it is necessity to develop safe, efficient and practical method to prepare azidoalkylamines. The main object of present invention is to get higher yield and purity by preparing salts and free bases from salts. Another object of the present invention is no chromatography separation technique is needed to pure the product.
SUMMARY OF THE INVENTION:
The present invention relates to the process for preparation of azidoalkylamine of formula-I and its various salts of formula-la. In one aspect, the present invention relates to the process for preparation of 1 -amino-4-azido butane of formula-II comprising the steps of;
(a) Reacting 1,4-dibromobutane with sodium azide in presence of solvent
(b) Isolating 1-amino-4-azido butane
In another aspect, the present invention provides the process for preparing mineral acid salts of l-amino-4-azido butane comprises;
(a) Dissolving 1-amino-4-azido butane in a suitable solvent
(b) Adding mineral acid solution
(c) Obtaining desired salt of 1 -amino-4-azido butane
In one another aspect, the present invention provides the process for preparing carboxylic acid salts of I -amino-4-azido butane comprises;
(a) Dissolving l-amino-4-azido butane in a suitable solvent
(b) Adding mineral acid solution
(c) Obtaining desired salt of 1 -amino-4-azido butane
In another aspect, the present invention provides process for preparing of free base of 1-

(a) Basifying the salt with suitable base
(b) Obtaining free base of 1 -amino-4-azido butane
DETAIL DESCRIPTION OF THE INVENTION:
The present invention relates to safe, economical and commercially feasible process for the preparation of azidoalkylamine of formula-I and its various salts of formula-la.In one embodiment, the present invention relates to the process for preparation of l-amino-4-azido butane of formula-II comprising the steps of;
(c) Reacting 1,4-dibromo butane with sodiumazide in presence of solvent
(d) extracting and Acidifying aqueous layer
(e) Isolating l-amino-4-azido butane
The process for preparation of l-amino-4-azido butane of formula-II depicted in the following reaction scheme-IThe suitable solvent used in step (a) is selected from the group consisting of polar solvents, The polar solvent is selected from, dimethylformamide, dimethylacetamide or mixture of two or more solvents. The reaction temperature for step (a) is 60-65°C.

The suitable solvent used for extraction in step (b) is selected from Dichloromethane,
Dichloroethane, Methyl tert-butyl ether or mixture of two or more solvents.
In accordance with another embodiment the present invention provides acid addition salts of
l-amino-4-azido butane. Wherein the acid is selected from the group consisting of mineral
acids, sulfonic acids, carboxylic acids.
The mineral acid is selected from hydrochloric acid, hydrobromic acid, sulphuric acid,
phosphoric acid, hydrofluoric acid. The sulfonic acid is selected from p-toluene sulfonic acid,
methanesulfonic acid, ethanesulfonic acid.
The carboxylic acid is selected from the group consisting of saturated fatty acids, aromatic
carboxylic acids, phenyl alkanoic acids, dicarboxylic acids, tricarboxylic acids, alphahydroxy
acids. The carboxylic acid is selected from Caprylic acid, Caprylic acid, Laurie acid, Myristic
acid, Palmitic acid, Stearic acid, arachidic acid, benzoic acid, salicylic acid, cinaamic acid,
isophthalic acid, phthalic acid, terephthalic acid, oxalic acid, malonic acid, succinic acid,
glutaric acid, adipic acid, frimaric acid, maleic acid, citric acid, isocitric acid, lactic acid,
ascorbic acid,mandelic acid, glyceric acid and the like.
In one embodiment, the present invention provides the process for preparing mineral acid
salts of 1-amino-4-azido butane comprises;
(a) Dissolving 1 -amino-4-azido butane in a suitable solvent
(b) Adding mineral acid solution
(c) Evaporating suitable solvent and stirring residue in solvent at ambient temperature
(d) Obtaining desired salt of l-amino-4-azido butane
The term suitable solvent includes water, lower alcohols, ketones, esters, ethers, C5-7 linear,
branched or cyclic, saturated or unsaturated hydrocarbons, nitriles, halogenated hydrocarbons
or mixture thereof.
The suitable solvents are selected from the group consisting of methanol, ethanol,
isopropanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl acetate, ethyl
acetate, isopropyl acetate, tetrahydrofuran, isopropylether, tert.butyl methyl ether,
acetonitrile, propionitrile, methylene chloride, chloroform, toluenes, cyclohexane, hexane,
heptanes or mixtures thereof.
The solvent for step (c) is selected from methyl tert butyl ether, isopropyl ether, hexane, cyclohexane or mixtures thereof.
The temperature for step (a) is 10-15°C.

In one another embodiment, the present invention provides the process for preparing carboxylic acid salts of l-amino-4-azido butane comprises;
(a) Dissolving 1 -amino-4-azido butane in a suitable solvent
(b) Adding mineral acid solution
(c) Obtaining desired salt of l-amino-4-azido butane
The term suitable solvent includes water, lower alcohols, ketones, esters, ethers, C5.7 linear,
branched or cyclic, saturated or unsaturated hydrocarbons, nitriles, halogenated hydrocarbons
or mixture thereof.
The suitable solvents are selected from the group consisting of methanol, ethanol,
isopropanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl acetate, ethyl
acetate, isopropyl acetate, tetrahydrofuran, isopropylether, tert.butyl methyl ether,
acetonitrile, propionitrile, methylene chloride, chloroform, toluenes, cyclohexane, hexane,
heptanes or mixtures thereof.
The temperature for step (a) is 35-45°C.
In another embodiment, the present invention provides process for preparing of free base of
l-amino-4-azido butane from l-amino-4-azido butane acid salt comprises;
(a) Basifying the salt with suitable base
(b) Extracting organic layer with solvent
(c) Obtaining free base of l-amino-4-azido butane
The term suitable base is inorganic base. The inorganic base is selected from hydroxides like
sodium hydroxide, potassium hydroxide, lithium hydroxide, carbonate salts of alkali and
alkaline earth metals like potassium carbonate, potassium bicarbonate, sodium carbonate,
sodium bicarbonate, cesium carbonate.
The term solvent in step (b) is selected from the group consisting of dichloromethane, ethyl
acetate, methyl tert butyl ether and the like.
The temperature for step (a) is 20-25°C.
The main object of the present invention is to provide high purity and high yield product by
preparing freebase from appropriate salts. More over the present invention does not required
further purification of free base.

The following examples explain various other embodiments without limiting the scope of the present invention.
Example-1: Preparation of l-amino-4-azido butane phosphate salt
To a solution of ortho-phosphoric acid in ethanol added lOOg l-amino-4-azido butane in
ethanol for 30 min at 10°C.white solid precipitated out during the addition. After stirring 3hrs
at RT, ethanol was evaprorated. Residue stirred with methyl tert butyl ether for 30 mins. The
solid was filtered, washed with methyl tert butyl ether and dried under high vaccum to obtain
90% of l-amino-4-azido butane phosphate salt.
Purity: 99-99.5%
Example-2: Preparation of l-amino-4-azido butane sulphate salt
To a solution of sulfuric acid in ethanol added lOOg l-amino-4-azido butane in ethanol for 30
min at 10°C. White solid precipitated out during the addition. After stirring 3hrs at RT,
ethanol was evaprorated. Residue stirred with methyl tert butyl ether for 30 mins. The solid
was filtered, washed with methyl tert butyl ether and dried under high vaccum to obtain 89%
of l-amino-4-azido butane sulphate salt.
Purity: 99-99.5%
Example-3: Preparation of l-amino-4-azido butane oxalate salt
To a solution of oxalic acid in acetone added t-amino-4-azido butane in acetone for 30 mins
at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 85% of 1-amino-4-azido butane oxalate salt.
Purity: 99-99.5%
Example-4: Preparation of l-amino-4-azido butane p-toluene sulfonate salt
To a solution of p-toluene sulfonic acid in acetone added 1-amino-4-azido butane in acetone
for 30 mins at 35-40°C. Solid precipitated out during the addition. After stirring lhr at 35-
40°C, the reaction mixture was cooled to 5-l0°C. Filtered the reaction mixture and washed
with acetone. Dried the solid at 50-55°C to obtain 18% of t-amino-4-azido butane p-toluene
sulfonate salt.
Purity: 99-99.5%
Example-5: Preparation of l-amino-4-azido butane 4-me thy I salicylate salt
To a solution of 4-methyl salicylic acid in acetone added l-amino-4-azido butane in acetone
for 30 mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-
45°C, the reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed

with acetone. Dried the solid at 50-55°C to obtain 90% of l-amino-4-azido butane 4-methyl
salicylate salt.
Purity: 99-99.5%
Example-6: Preparation of l-amino-4-azido butane isophthalate salt
To a solution of isophthalic acid in acetone added l-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 87% of 1-amino-4-azido butane isophthalate
salt.
Purity: 99-99.5%
ExampIe-7: Preparation of l-amino-4-azido butane maloniate salt
To a solution of malonic acid in acetone added 1-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 84% of l-amino-4-azido butane maloniate salt.
Purity: 99-99.5%
Example-8: Preparation of l-amino-4-a/ido butane aspartate salt
To a solution of aspartic acid in acetone added l-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 86% of 1-amino-4-azido butane aspartate salt.
Purity: 99-99.5%
Example-9: Preparation of l-amino-4-azido butane ascorbate salt
To a solution of ascorbic acid in acetone added l-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 91% of l-amino-4-azido butane ascorbate salt.
Purity: 99-99.5%
Example-10: Preparation of l-amino-4-azido butane cinnamate salt
To a solution of cinnamic acid in acetone added l-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring I hr at 40-45°C; the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 82% of l-amino-4-azido butane cinnamate salt. D....:+.,. no no c«/_

Example-11: Preparation of l-amino-4-azido butane benzoate salt
To a solution of benzoic acid in acetone added l-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 90% of 1 -amino-4-azido butane benzoate salt.
Purity: 99-99.5%
Example-12: Preparation of l-amino-4-azido butane isocitrate salt
To a solution of isocitric acid in acetone added l-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 87% of l-amino-4-azido butane isocitrate salt.
Purity: 99-99.5%
Example-13: Preparation of l-amino-4-azido butane glycerate salt
To a solution of glyceric acid in acetone added 1-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C) the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 83% of l-amino-4-azido butane glycerate salt.
Purity: 99-99.5%
Example-14: Preparation of l-amino-4-azido butane lactate salt
To a solution of lactic acid in acetone added l-amino-4-azido butane in acetone for 30 mins
at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 81% of l-amino-4-azido butane lactate salt.
Purity: 99-99.5%
Example-15: Preparation of l-amino-4-azido butane malate salt
To a solution of malic acid in acetone added 1-amino-4-azido butane in acetone for 30 mins
at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C, the
reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 84% of 1-amino-4-azido butane malate salt.
Purity: 99-99.5%
Example-16: Preparation of l-amino-4-azido butane mandelate salt
To a solution of mandelic acid in acetone-added l-amino-4-azido butane in acetone for 30
mins at 40-45°C. Solid precipitated out during the addition. After stirring lhr at 40-45°C. the

reaction mixture was cooled to 20-25°C. Filtered the reaction mixture and washed with
acetone. Dried the solid at 50-55°C to obtain 85% of 1-amino-4-azido butane mandelate salt.
Purity: 99-99.5%
Example-17: Preparation of l-amino-4-azido butane
To the mixture of 20ml dimethyl formamide and 20gm 1,4-dibromobutane added sodium
azide solution (20gm in 60 ml water) and stirred at 60-65 °C for 8hrs. The reaction mixture
was cooled to 25-30°C. Charged 100ml water and 20 ml methyl tert butyl ether at 35°C. The
reaction mixture was separated and extracted the aqueous layer with methyl tert butyl ether.
Added dilute HC1 and triphenyl phosphene solution to methyl tert butyl ether layer at 10-
15°C and stirred for 8 hrs at 20-25°C.the resultant mixture was filtered and washed the cake
with dil HC1 solution. Separated aqueous layer and washed with methyl tert butyl ether. The
aqueous layer was cooled to 10-15°C and added 30gm sodium hydroxide flakes. The
resultant mixture was maintained at 15-20°C for I hr. The oily layer was dissolved in methyl
tert butyl ether. The resultant methyl tert butyl ether layer was distilled out at 40-45°C to get
55% l-amino-4-azido butane.
GC Purity: 95-97%
Example-18: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane phosphate salt
To the 1-amino-4-azido butane phosphate salt added 140ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 95% free base of 1 -amino-4-azido butane.
GC Purity: 99-99.5%
Example-19: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane oxalate salt
To the l-amino-4-azido butane oxalate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 73% free base of I -amino-4-azido butane.
GC Purity: 99-99.5%
Example-20: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane p-toluene sulphonate salt
To the l-amino-4-azido butane p-toluene sulphonate salt added 50ml potable water. Charged

temperature. Extracted with dichloromethane and washed with water. Collected organic layer and evaporated under high vaccum to get 45% free base of l-amino-4-azido butane. GC Purity: 99-99.5%
Example-21: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido butane sulphate salt
To the l-amino-4-azido butane sulphate salt added 140ml potable water. Charged sodium hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature. Extracted with dichloromethane and washed with water. Collected organic layer and evaporated under high vacuum to get 95% free base of l-amino-4-azido butane. GC Purity: 99-99.5%
Example-22: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido butane 4-methyl salicylate salt
To the 1 -amino-4-azido butane 4-methyl salicylate salt added 50ml potable water. Charged sodium hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature. Extracted with dichloromethane and washed with water. Collected organic layer and evaporated under high vacuum to get 89% free base of 1-amino-4-azido butane. GC Purity: 99-99.5%
Example-23: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido butane isophthalate salt
To the l-amino-4-azido butane isophthalate salt added 50ml potable water. Charged sodium hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature. Extracted with dichloromethane and washed with water. Collected organic layer and evaporated under high vacuum to get 90% free base of l-amino-4-azido butane. GC Purity: 99-99.5%
Example-24: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido butane maloniate salt * To the l-amino-4-azido butane maloniate salt added 50ml potable water. Charged sodium hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature. Extracted with dichloromethane and washed with water. Collected organic layer and evaporated under high vacuum to get 81% free base of l-amino-4-azido butane. GC Purity: 99-99.5%

Example-25: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido butane aspartate salt
To the l-amino-4-azido butane aspartate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 83% free base of l-amino-4-azido butane.
GC Purity: 99-99.5%
Example-26: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane ascorbate salt
To the l-amino-4-azido butane ascorbate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloro methane and washed with water. Collected organic layer and
evaporated under high vacuum to get 90% free base of l-amino-4-azido butane.
GC Purity: 99-99.5%
Example-27: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane cinnamate salt
To the l-amino-4-azido butane cinnamate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 79% free base of 1 -amino-4-azido butane.
GC Purity: 99-99.5%
ExampIe-28: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane benzoate salt
To the 1-amino-4-azido butane benzoate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 89% free base of l-amino-4-azido butane.
GC Purity: 99-99.5%
Example-29: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane isocitrate salt
To the l-amino-4-azido butane isocitrate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and

GC Purity: 99-99.5%
Example-30: Preparation of freebase of l-araino-4-azido butane from l-amino-4-azido
butane glycerate salt
To the l-amino-4-azido butane glycerate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 79% free base of 1 -amino-4-azido butane.
GC Purity: 99-99.5%
Example-31: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane lactate salt
To the l-amino-4-azido butane lactate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 80% free base of l-amino-4-azido butane.
GC Purity: 99-99.5%
Example-32: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane malate salt
To the l-amino-4-azido butane malate salt added 50ml potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 81% free base of l-amino-4-azido butane.
GC Purity: 99-99.5%
Example-33: Preparation of freebase of l-amino-4-azido butane from l-amino-4-azido
butane mandelate salt
To the l-amino-4-azido butane mandelate salt added 50mt potable water. Charged sodium
hydroxide solution slowly for a period of 30 mins and stirred for 2 hr at ambient temperature.
Extracted with dichloromethane and washed with water. Collected organic layer and
evaporated under high vacuum to get 82% free base of 1 -amino-4-azido butane.
GC Purity: 99-99.5%