FIELD OF THE INVENTION
The present invention provides a process for preparation of an acid salt of fluorinated alkylamine. These compounds are very useful in the organic synthesis and have wide applications as intermediate in pharmaceutical and agricultural industrially.

BACKGROUND OF THE INVENTION
The fluorinated alkylamines are generally prepared by reacting fluorinated alkyl halide with ammonia.
The literature available, particularly, describes process for preparation of 2,2,2-trifluoroethylamine but doesn’t provides an economic and industrially applicable process for its salt. The 2,2,2-trifluoroethylamine is a high volatile liquid at room temperature and need to be stored at low temperature. It is highly flammable and toxic for human health, it should be handled carefully during commercial scale ups and transportation. However, their acid salts are devoid of any handling issues.
Tetrahedron Letters, 35(19), 3119-22; 1994 provides a process for preparation of 2,2,2-trifluoroethylamine hydrochloride by hydrolysis of 2,2,2-trifluoro-N-(phenylmethylene)-ethanamine in hydrochloric acid. 2,2,2-trifluoro-N-(phenylmethylene)-ethanamine was prepared from aniline and 2,2,2-trifluoroacetaldehyde in presence of p-methylbenzenesulfonic acid. The process generates a large quantity of by-products that would need multiple steps for removal.
US 6,534,683 provides a process for preparation of fluorinated alkyl amine by reacting fluorinated alkyl halide with ammonia using alkanediol as solvent. It doesn’t provides any economic process for preparation of 2,2,2-trifluoroethylamine hydrochloride salt.
CN 105801428 provides a process for preparation of trifluoroethylamine hydrochloride salt by reacting trifluoroethylamine with aqueous hydrogen chloride in presence of ethanol-water azeotrope or near azeotropic mixture. However, removal and recovery of solvent is very challenging due to the azeotropes.
Therefore, there is a need to develop an economical and industrially feasible process for preparation of an acid salt of fluorinated alkylamine.

OBJECT OF THE INVENTION
The main object of present invention is to provide an economical and industrially doable process for preparation of an acid salts of fluorinated alkylamine of formula I from fluorinated alkylhalide.

SUMMARY OF THE INVENTION
In first aspect, the present invention provides a process for preparing a salt of fluorinated alkylamine of formula I,

Formula I
wherein R is fluoroalkyl, HX is an acid and n is 1-3,
comprising the steps of:
a) reacting a compound of formula II,
1
Formula II
wherein R is fluoroalkyl , X1 is chlorine, fluorine, bromine or Iodine and n is 1-3,
with ammonia in a first organic solvent to obtain a compound of formula III;

Formula III
wherein R and n are mentioned above,
b) contacting the compound of formula III with an acid in a second organic solvent to isolate the compound of formula I.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, a compound of formula I refers to salt of fluorinated alkylamine.
As used herein, salts of fluorinated alkylamine refers salts with hydrochloric acid, hydrobromic acid, hydro iodic acid, hydrofluoride, sulfuric acid, phosphoric acid, citric acid, anhydrous citric acid, mandelic acid, succinic acid and methanesulfonic acid, p-toluenesulfonic acid, fluoroboric acid or the like.
As used herein, acid refers to hydrochloric acid, hydrobromic acid, hydro iodic acid, hydrofluoride, sulfuric acid, phosphoric acid, citric acid, anhydrous citric acid, mandelic acid, succinic acid and methanesulfonic acid, p-toluenesulfonic acid, fluoroboric acid or the like.
As used herein, fluoroalkyl may be selected from C1 to C3 alkyl substituted with one or more fluorine groups.
As used herein, first organic solvent may be selected from N-methylpyrrolidone and glycols and ethers such as 2-(2-ethoxyethoxy)-ethanol, triethyleneglycol dimethylether, octane-1,8-diol, propylene glycol or ethylene glycol and the like.
As used herein, second organic solvent may be selected from acetonitrile, ethanol, methanol, acetone, toluene, hexane, pentane, cyclohexane, chlorobenzene, xylenes, benzotrifluoride dichloromethane and benzonitrile or the like.
In one embodiment, the process is carried out using anhydrous ammonia.
In one embodiment, anhydrous ammonia have moisture less than 0.1% and preferably in the range 0-0.1%. The low moisture content in the process prevents formation of fluorinated alcohol and other impurities and corrosion of reactor.
In one embodiment, the molar ratio of ammonia to the compound of formula I may be selected in a range of 3-4.
In one embodiment, initially ammonia is added to the solvent at a temperature range of -10°C to -30°C.
In an embodiment, a compound of formula II is added to the solvent at a temperature range of 150°C -200°C.
In one embodiments, the step-a) is carried out in low-pressure range of 10-18 Kg/cm2.
In one embodiment, a compound of formula II may be added continuously or lot wise in a mixture of ammonia and solvent.
As used herein, lot wise addition refers to addition in one or more lots.
In one embodiment, a compound of formula II is added continuously in a mixture of ammonia and solvent.
The continuous and lots wise addition of a compound of formula II in the mixture of ammonia and solvent helps to regulate pressure in low ranges, control process exothermicity and avoid use of high-pressure range.
In one embodiment, reaction mixture may contain unreacted ammonia and/or the compound of formula II that may be recovered and recycled back to the reactor.
In another embodiment, the present invention provides a process for preparation of a compound of formula I comprising the steps of:
a) reacting a compound of formula II with ammonia in a first organic solvent to obtain a reaction mixture;
b) recycling unreacted ammonia and the compound of formula II;
c) contacting a compound of formula III with an acid to isolate a compound of formula I.
In one embodiment, a compound of formula III is isolated or used in-situ for preparation of the compound of formula I. Preferably, the reaction mixture from step a) is washed and taken in a second organic solvent and proceeded for the next step.
The compound of formula III for present invention can also be prepared by method known in an Indian application no. 585/DEL/2010, now patent no. 295223.
In one embodiment, the molar ratio of acid may be selected in range 1-1.5%.
In one embodiment, the reaction is carried out in absence of catalyst.
In a particular embodiment, acid used for present invention is anhydrous.
In a preferred embodiment, anhydrous acid are hydrogen chloride, hydrogen fluoride hydrogen iodide and hydrogen bromide.
In one embodiment, the compound of formula I may be purified using solvent.
In another embodiment, the present invention provides a process for preparation of a compound of formula I comprising the steps of:
a) preparing a compound of formula III;
b) adding first organic solvent and passing an acid to the reaction mixture of step-a);
c) isolating the compound of formula I.
In one embodiment, crude compound of formula I is dissolved in a second organic solvent and purified to obtain pure compound of formula I.
In another embodiment, the present invention provides a process for preparation of a compound of formula I having purity greater than 99%.
The product may be isolated using a method selected from filtration, extraction, distillation, boil-off, crystallization or combination thereof.
The completion of the reaction may be monitored by any one of chromatographic techniques such as thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), Gas chromatography (GC), liquid chromatography (LC) and alike.
The reagents used in the above process are obtained commercially.
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: Preparation of 2,2,2-trifluoroethylamine hydrogen chloride
Ethylene glycol (2584g) was charged in a reactor and cooled to below -10°C. Anhydrous ammonia gas was charged (150g) into the reactor at below -10°C and heated slowly to room temperature after addition. The reaction mass was heated to 190°C and 2,2,2-trifluoroethylchloride (270g) was added in 7 equal lots into the reactor. The reaction mass was stirred at 190°C for 10-15 hours and cooled to 40°C. Unreacted 2,2,2-trifluoroethylchloride and ammonia were separated from the reaction mass by heating at 40°C to 150°C. The reaction mass was concentrated and diluted with toluene. The reaction mass was cooled and anhydrous hydrogen chloride (1.1 moles) was added in the reaction mass slowly. The reaction mass was filtered and purified in acetonitrile to isolate 2,2,2-trifluoroethylamine hydrogen chloride.
Purity (GC %): 99%; Yield: 87%
Example 2: Preparation of 2,2,2-trifluoroethylamine hydrogen chloride
Methylene glycol (250g) was charged in a reactor and cooled to below -10°C. Anhydrous ammonia gas (15g) was added into the reactor and heated to room temperature. The reaction mass was heated to 170°C and 2,2,2-trifluoroethylchloride (27g) was charged in the reactor in 10 equal lots. The reaction mass was stirred at 170°C for 15 hours. The reaction mass was cooled to 50°C and unreacted 2,2,2-trifluoroethylchloride and ammonia were separated. The reaction mass was concentrated and hexane was added. The reaction mass was cooled to 30°C and anhydrous hydrogen chloride (1.2 moles) was added. The reaction mass was filtered after hydrogen chloride addition and 2,2,2-trifluoroethylamine hydrogen chloride was isolated.
Purity (GC %): 98%; Yield: 88%
Example 3: Preparation of 2,2-difluoroethylamine hydrogen chloride
Ethylene glycol (18 moles) was charged in a reactor and cooled to below -10°C. Anhydrous ammonia gas (3.5 moles) was added in the reactor and heated to room temperature. The reaction mass was heated to 170°C and 2,2-difluoroethylchloride (1 mole) was added in the reaction mass in 13 equal lots and stirred for 15 hours. The reaction mass was to cooled to 60°C and unreacted 2,2-difluoroethylchloride and ammonia was separated. The reaction mass was concentrated on rota evaporator and hexane was added. The reaction mass was cooled to 20°C and hydrogen chloride (1.1 moles) was passed slowly in the reaction mass. After addition, the reaction mass was filtered and filtered solid was dissolved in acetonitrile. Again, the solution of filtered solid in acetonitrile was filtered and purified in water to isolated product.
Purity (GC %): 99%; Yield: 90%
Example 4: Preparation of 2-fluoroethylamine hydrogen bromide
Ethylene glycol (17 moles) was charged in a reactor and cooled to -20°C. Anhydrous ammonia gas (3.6 moles) was added in the reactor and slowly heated to room temperature. The reaction mass was heated to 170°C and 2-fluoroethylchloride (1 mole) was added in 17 equal lots. The reaction mass was stirred and cooled to 50°C. Unreacted 2-fluoroethylchloride and ammonia were separated and concentrated the reaction mass on rota evaporator. Hexane was added in the reaction mass and cooled to 30°C. The hydrogen bromide (1.1 moles) was purged in the reaction mass and filtered the reaction mass. The acetonitrile was added in the filtered solid and filtered again. The solid was purified in water and product was isolated.
Purity (GC %): 99%; Yield: 86%
Example 5: Preparation of 2,2,2-trifluoroethylamine hydrogen fluoride
Ethylene glycol (16 moles) was charged in a reactor and cooled to -30°C. Anhydrous ammonia gas (3.5 moles) was added in the reactor and slowly reaction mass was heated to room temperature. Further, reaction mass was heated to 190°C and 2,2,2-trifluoroethylchloride (1 moles) was added in the reaction mass in 8 equal lots and stirred for 15 hours. The reaction mass was cooled to 50°C and unreacted 2,2,2-trifluoroethylchloride and ammonia were separated. The reaction mass was concentrated on rota evaporator and diluted with toluene. The reaction mass was cooled 30°C and hydrogen fluoride (1.1 moles) was added. The reaction mass was filtered after addition and purified in acetonitrile and 2,2,2-trifluoroethylamine hydrogen fluoride was isolated.
Purity (GC %): 99%; Yield: 87%
Example 6: Preparation of 2,2,2-trifluoroethylamine hydrogen fluoride
Propylene glycol (16 moles) was charged in a reactor and cooled to -10°C. Anhydrous ammonia gas (3.7 moles) was added in the reactor and reaction mass was heated to room temperature. Further, reaction mass was heated to 190°C and a 2,2,2-trifluoroethylchloride (1 mole) was added in the reactor in 12 equal lots. The reaction mass was stirred for 16 hours. The reaction mass was cooled to 50°C and unreacted 2,2,2-trifluoroethylchloride and ammonia were separated. The reaction mass was concentrated and diluted with pentane. Then, the reaction mass was cooled to 30°C and hydrogen fluoride (1.1 moles) was added. After addition, the reaction mass was filtered and filtered solid was purified in acetonitrile to isolate product.
Purity (GC %): 99%; Yield: 85%
Example 7: Preparation of 2,2,2-trifluoroethylamine hydrogen chloride
Propylene glycol (18 moles) was charged in a reactor and cooled to -10°C. Anhydrous ammonia gas (3.5 moles) was added in the reactor and heated to room temperature. Again, The reaction mass was heated to 195°C and 2,2,2-trifluoroethylchloride (1 mole) was added in 14 equal lots and stirred for 15 hours. The reaction mass was cooled and unreacted 2,2,2-trifluoroethylchloride and ammonia were separated. The reaction mass was concentrated on rota evaporator and toluene was added. The reaction mass was cooled to 30°C and hydrogen chloride (1.1 moles) was added slowly. Then, the reaction mass was filtered and filtered solid was purified in acetonitrile and product was isolated.
Purity (GC %): 99%; Yield: 88%
Example 8: Preparation of 2,2,2-trifluoroethylamine hydrogen bromide
Propylene glycol (16 moles) was charged in a reactor and cooled to -10°C. Anhydrous ammonia gas (3.6 moles) was added in the reactor and heated to room temperature. Further, the reaction mass was heated to 190°C and 2,2,2-trifluoroethylchloride (1 mole) was added in 15 equal lots and stirred for 14 hours. The reaction mass was cooled to 50°C and unreacted 2,2,2-trifluoroethylchloride and ammonia were separated. The reaction mass was concentrated on rota evaporator and diluted with xylene. The reaction mass was cooled to 30°C and hydrogen bromide (1.1 moles) was added. The reaction mass was filtered, purified and product was isolated.
Purity (GC %): 99%; Yield: 85%.

CLAIMS:WE CLAIM:
1. A process for preparing a salt of fluorinated alkylamine of formula I,

Formula I
wherein R is fluoroalkyl, HX is an acid and n is 1-3,
comprising the steps of:
a) reacting a compound of formula II,
1
Formula II
wherein R is fluoroalkyl , X1 is chlorine, fluorine, bromine or Iodine and n is 1-3,
with ammonia in a first organic solvent to obtain a compound of formula III;

Formula III
wherein R and n are mentioned above,
b) contacting the compound of formula III with an acid in a second organic solvent to obtain the compound of formula 1; and
c) isolating the compound of formula I.
2. A process for preparation of a compound of formula I, comprising the steps of:
a) contacting a compound of formula III with a second organic solvent to obtain a reaction mixture;

Formula III
wherein R and n are mentioned above,
b) passing an acid to the reaction mixture of step-a); and
c) isolating the compound of formula I.
3. A process as claimed in claim 1, wherein the unreacted ammonia and the compound of formula II is recycled to step a).
4. The process as claimed in claim 1 and 2, wherein the first organic solvent is selected from a group consisting of N-methylpyrrolidone, glycol, 2-(2-ethoxyethoxy)-ethanol, triethyleneglycol dimethylether, octane-1,8-diol, propylene glycol and ethylene glycol or a mixture thereof.
5. The process as claimed in claim 1 and 2, wherein the acid is selected from a group consisting of hydrochloric acid, hydrobromic acid, hydrofluoride, sulfuric acid, phosphoric acid, citric acid, anhydrous citric acid, mandelic acid, succinic acid, methanesulfonic acid, p-toluenesulfonic acid and fluoroboric acid or a mixture thereof.
6. The process as claimed in claim 1 and 3, wherein the second organic solvent is selected from a group consisting of acetonitrile, ethanol, methanol, acetone, toluene, hexane, pentane, cyclohexane, chlorobenzene, xylenes, benzotrifluoride dichloromethane and benzonitrile or a mixture thereof.
7. The process as claimed in claim 1 and 2, wherein the ammonia is anhydrous and have moisture content less than 0.1%.
8. The process as claimed in claim 1 and 2, wherein, a compound of formula II is added continuously in a mixture of ammonia and solvent in 5-30 lots.
9. The process as claimed in claim 8, wherein, the compound of formula II is added continuously in a mixture of ammonia and solvent in 5-15 lots.

10. The process as claimed in claim 1, wherein, the step-a) is carried out in a pressure range of 5-18 Kg/cm2.