BACKGROUND OF THE INVENTION
1-{2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidine-4-carbothioamide, formula I, is used as an important intermediate for synthesizing the agrochemical and pharmaceutical products.

Formula I
US Patent No. 9,604,962 describes a process for preparation of compound of formula I by reacting 1-{2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidine-4-carbonitrile having structural formula II with hydrogen sulfide gas to obtain compound of formula I having 3% of its regioisomer.

Formula II
The said patent uses hydrogen sulfide gas that causes safety and health concerns. The inventors have proposed an industrially viable process disclosed and claimed in Indian Patent Application 201711032406, which circumvents the use of hydrogen sulfide gas in the process and gives the compound of formula I in a purity of 90-95%. The inventors of the present invention have evolved a process for purification of the compound of formula I to achieve higher purity of 97-99.5%. The present invention provides an improvement of the process of Indian Patent Application 201711032406.

OBJECT OF THE INVENTION
The main object of the present invention is to provide an industrially advantageous and efficient process for purification of a compound of formula I.

Formula I

SUMMARY OF THE INVENTION
In first aspect, the present invention relates to process for purification of compound of formula I,

Formula I

comprising the steps of:
a) providing a mixture of an impure compound of formula I and chlorinated solvent in a reactor;
b) refluxing the reaction mixture of step a); and
c) isolating the pure compound of formula I.

In second aspect, the present invention relates to process for purification of compound of formula I,

Formula I
comprising the steps of:
a) dissolving an impure compound of formula I in alcoholic solvent;
b) adding anti-solvent to the solution of step a); and
c) isolating the pure compound of formula I.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, the impure of compound of formula I, have more than 3% of regioisomer impurity and purity of not more than 95%.

Regioisomer Impurity
In an embodiment of first aspect, a mixture of impure compound of formula I and chlorinated solvent is added in a reactor.
The chlorinated solvent is selected from dichloromethane, chloroform, chlorobenzene, benzyl chloride and alike or mixture thereof.
The resulting reaction mixture is heated at reflux temperature for 30 minutes to 4 hours. Then, the reaction mixture is filtered in hot condition to obtain pure compound of formula I.
The pure compound of formula I, referred herein, having purity atleast 97%; regioisomer impurity not more than 2.5%.
In an embodiment of second aspect, the compound of formula I is dissolved in an alcoholic solvent at a temperature in the range of 50ºC to 80ºC.
The alcoholic solvent is selected from methanol, ethanol, propanol, isopropanol and alike or mixture thereof.
After complete dissolution of the compound of formula I, the reaction mass is filtered and the filtrate is cooled at a temperature in the range of 30ºC to 60ºC. Then, anti-solvent is added dropwise to the filtrate till precipitation of material. The anti-solvent is the solvent which precipitate out the material from the reaction mixture.
The anti-solvent used for precipitation of material is water or a chlorinated solvent.
Usually, the material is precipitated out within 1 to 4 hours. The precipitated off-white crystalline solid was filtered out and dried to obtain pure compound of formula I having purity more than 99% and regioisomer impurity not more than 1%.
A compound of formula I is prepared by a process as disclosed in IN 201711032406, comprising the steps of:
a) reacting piperidine-4-carboxamide with chloroacetyl chloride in an aprotic solvent to obtain 1-(2-chloroacetyl) piperidine-4-carbonitrile;
b) converting 1-(2-chloroacetyl) piperidine-4-carbonitrile to a compound of formula II

Formula II
by reacting it with 5-methyl-3-trifluoromethylpyrazole in presence of a base;
c) reacting a compound of formula II with a salt of sulfide to obtain the compound of formula I having more than 3% of regioisomer impurity.

Regioisomer Impurity
The presence of regioisomer impurity and purity of pure compound of formula I can be monitored by any one of chromatographic techniques such as Thin layer chromatography (TLC), High pressure liquid chromatography (HPLC), Ultra-pressure liquid chromatography (UPLC) and the like.
The pure compound of formula I, obtained by the process of present invention, may be used as a key intermediate for preparing agrochemical and pharmaceutical products.
The compound of formula V, IV, II, I and 5-methyl-3-trifluoromethylpyrazole which are used as a starting material can be prepared by methods known through IN201711032406 or any method known in the art or can be obtained commercially.
It is against this and other backgrounds, which shall be filed in a detailed manner in complete specifications, in due course, the present invention is brought out and explained in following non-limiting examples.
It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention and specific examples provided herein without departing from the spirit and scope of the invention.
Thus, it is intended that the present invention covers the modifications and variations of this invention that come within the scope of any claims and their equivalents.

EXAMPLES
Example 1: Preparation of 1-(2-chloroacetyl) piperidine-4-carbonitrile
Chloroacetyl chloride (201 g) was added dropwise to a slurry of piperidine-4-carboxamide (91 g), N,N-dimethyl formamide (315g) and dichloromethane (789 g moles) at a temperature of 20°C over the period of one and half hours. After complete addition of chloroacetyl chloride, temperature of the reaction mass was increased to 50°C to obtain a clear homogeneous solution. After the reaction completion, the reaction mass was cooled to 20°C and washed with brine solution and sodium bicarbonate solution to remove side products. Then the organic layer was concentrated to get the titled compound.
Yield: 80%
Purity (by GC): 90%.

Example 2: Preparation of 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] acetyl]-4-piperidinecarbonitrile
A solution of 5-methyl-3-trifluoromethylpyrazole (9.3 g, 62 mmol) and 45% aqueous potassium hydroxide solution (7.79 g, 62 mmol) in N,N-dimethylformamide (25 mL) was cooled to 5°C and 1-(2-chloroacetyl)-4-piperidinecarbonitrile (11.2 g, 60 mmol) was added. The reaction mixture was stirred for 8 hours at 5-10° C., then diluted with water (100 mL), and filtered. The filtered cake was washed with water and dried at 50° C. in a vacuum-oven to give the titled compound as a solid.

Example 3: Preparation of 1-{2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] acetyl}piperidine-4-carbothioamide (formula I).
1-{2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidine-4-carbonitrile (25g), water (100ml), 1,4-dioxane (99.51ml), sodium hydrosulfide hydrate (55g) and diethylamine hydrochloride (63.87g) were added to the reactor to obtain a reaction mixture. The reaction mixture was heated at 55°C under stirring for 8 to 10 hours. After completion of the reaction, monitored by HPLC, the reaction mixture was cooled to a temperature below 30°C and thereafter adding water (500ml), further stirred the reaction mixture for 30 minutes. Then the reaction mixture is filtered to obtain 28.6g of title compound. The filtrate was taken for next crop product recovery. The titled compound was analysed by HPLC having following results.
Purity (HPLC) : 95.43%
Regioisomer Impurity : 3.91%
Unreacted starting intermediate : 0.58%

Example 4: Preparation of 1-{2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] acetyl}piperidine-4-carbothioamide (formula I).
1-{2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidine-4-carbonitrile (25g), water (100ml), 1,4-dioxane (99.51ml), sodium hydrosulfide hydrate (55g) were added to the reactor to obtain a reaction mixture. The reaction mixture was heated at 55°C under stirring for 8 to 10 hours. After completion of the reaction, monitored by HPLC, the reaction mixture was cooled to a temperature below 30°C and thereafter adding water (500ml), further stirred the reaction mixture for 30 minutes. Then the reaction mixture is filtered to obtain 28.6g of title compound. The filtrate was taken for next crop product recovery. The titled compound was analysed by HPLC having following results.
Purity (HPLC) : 94.43%
Regioisomer Impurity : 4.01%
Unreacted starting intermediate : 0.58%

Example 5: Preparation of 1-{2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] acetyl}piperidine-4-carbothioamide (formula I).
1-{2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidine-4-carbonitrile (25g), water (100ml), 1,4-dioxane (99.51ml), sodium sulfide (60g) and diethylamine hydrochloride (63.87g) were added to the reactor to obtain a reaction mixture. The reaction mixture was heated at 55°C under stirring for 8 to 10 hours. After completion of the reaction, monitored by HPLC, the reaction mixture was cooled to a temperature below 30°C and thereafter adding water (500ml), further stirred the reaction mixture for 30 minutes. Then the reaction mixture is filtered to obtain 28.6g of title compound. The filtrate was taken for next crop product recovery. The titled compound was analysed by HPLC having following results.
Purity (HPLC) : 94.43%
Regioisomer Impurity : 3.71%
Unreacted starting intermediate : 0.68%

Example 6: Purification of compound of formula I using dichloromethane.
The mixture of compound of formula I (28.6g) and dichloromethane (170ml) was added in a reactor. Then, the resulting reaction mixture was refluxed for one hour and then filtered in hot condition to obtain 25.96g of pure compound of formula I. The pure compound of formula I was analyzed by HPLC having following results.
Purity (HPLC) : 97.27%
Regioisomer Impurity : 2.52%

Example 7: Purification of compound of formula I using benzyl chloride.
The mixture of compound of formula I (28.6g) and benzyl chloride (150ml) was added in a reactor. Then, the resulting reaction mixture was refluxed for one hour and then filtered in hot condition to obtain 25.96g of pure compound of formula I. The pure compound of formula I was analyzed by HPLC having following results.
Purity (HPLC) : 97.50%
Regioisomer Impurity : 2.12%

Example 8: Purification of compound of formula I using methanol.
Compound of formula I (25.96g) was dissolved in methanol (282.82ml) at a temperature of 60-70ºC. Once the compound was dissolved completely, filtered the mass to remove the insoluble particles. Water (112ml) was added dropwise to the filtrate at 45-50°C to precipitate off-white crystalline solids. The precipitate off-white crystalline solids were filtered out and dried to obtain 13.9g of pure compound of formula I. The filtrate was taken for next purification cycle. The pure compound of formula I was analyzed by HPLC having following results:
Purity (HPLC) : 99.58%
Regioisomer Impurity : 0.42%
Unreacted starting intermediate : Nil

Example 9: Purification of compound of formula I using ethanol.
Compound of formula I (25.96g) was dissolved in ethanol (250ml) at a temperature of 60-70ºC. Once the compound was dissolved completely, filtered the mass to remove the insoluble particles. Water (100ml) was added dropwise to the filtrate at 45-50°C to precipitate off-white crystalline solids. The precipitate off-white crystalline solids were filtered out and dried to obtain 13.9g of pure compound of formula I. The filtrate was taken for next purification cycle. The pure compound of formula I was analyzed by HPLC having following results:
Purity (HPLC) : 99.68%
Regioisomer Impurity : 0.32%
Unreacted starting intermediate : Nil

Example 10: Purification of compound of formula I using methanol.
Compound of formula I (25.96g) was dissolved in methanol (282.82ml) at a temperature of 60-70ºC. Once the compound was dissolved completely, filtered the mass to remove the insoluble particles. Dichloromethane (100ml) was added dropwise to the filtrate at 45-50°C to precipitate off-white crystalline solids. The precipitate off-white crystalline solids were filtered out and dried to obtain 13.9g of pure compound of formula I. The filtrate was taken for next purification cycle. The pure compound of formula I was analyzed by HPLC having following results:
Purity (HPLC) : 99.38%
Regioisomer Impurity : 0.52%
Unreacted starting intermediate : Nil

Example 11: Purification of compound of formula I using ethanol.
Compound of formula I (25.96g) was dissolved in ethanol (250ml) at a temperature of 60-70ºC. Once the compound was dissolved completely, filtered the mass to remove the insoluble particles. dichloromethane (100ml) was added dropwise to the filtrate at 45-50°C to precipitate off-white crystalline solids. The precipitate off-white crystalline solids were filtered out and dried to obtain 13.9g of pure compound of formula I. The filtrate was taken for next purification cycle. The pure compound of formula I was analyzed by HPLC having following results:
Purity (HPLC) : 99.28%
Regioisomer Impurity : 0.72%
Unreacted starting intermediate : Nil

We Claims:
1. A process for purification of a compound of formula I,

Formula I
comprising the steps of:
a) dissolving an impure compound of formula I in an alcoholic solvent;
b) adding anti-solvent to the solution of step a); and
c) isolating the pure compound of formula I.

2. A process for purification of compound of formula I,

Formula I

comprising the steps of:
a) providing a mixture of an impure compound of formula I and a chlorinated solvent in a reactor;
b) refluxing the reaction mixture of step a) and filtered at 30 to 40ºC and
c) isolating the pure compound of formula I.
wherein the isolated compound of formula I having purity more than 97% and regioisomer impurity not more than 2.5%.

3. A process for purification of compound of formula I,

Formula I
comprising the steps of:
a) dissolving compound of formula I in alcoholic solvent at a temperature selected in the range of 50ºC to 80ºC followed by filtration;
b) cooling the filtered solution at a temperature selected in the range of 30ºC to 60ºC.
c) adding anti-solvent to the cooled solution of step i) till precipitation; and
d) isolating the pure compound of formula I.
wherein the isolated compound of formula I having purity more than 99% and regioisomer impurity not more than 0.5%.

4. The process as claimed in claims 2 and 3, wherein anti-solvent is selected from a group consisting of water, dichloromethane, chloroform, chlorobenzene, benzyl chloride or a mixture thereof.

5. The process as claimed in claim 2, wherein the chlorinated solvent is selected from a group consisting of dichloromethane, chloroform, chlorobenzene, benzyl chloride or a mixture thereof.

6. The process as claimed in claims 1 and 3, wherein an alcoholic is solvent selected from a group consisting of methanol, ethanol, propanol, isopropanol or a mixture thereof.

7. The process as claimed in claim 5, wherein precipitation occurs in a time period of 1 to 4 hours.