DESC:Field of the Invention
The present invention relates to the novel and efficient process for the preparation of Gabapentin.

Background of the Invention
Gabapentin is a pharmaceutical compound used for the treatment of epilepsy and other cerebral disorders. It is chemically known as 1-aminomethyl-1-cyclohexaneacetic acid (see below Formula I).

Formula (I): Structure of Gabapentin

Gabapentin has been successfully used to treat and/or control seizures associated with cerebral diseases including, for example, epilepsy. Gabapentin has also been used to manage post-herpetic neuralgia (i.e., the pain after "shingles") and it may also be useful for mood stabilization and treating anxiety.

Gabapentin, its process of preparation and use was first disclosed by Warner-Lambert Co. in US 4,024,175 and US 4,087,544 respectively. A number of processes are known in prior art for the preparation of Gabapentin. For instance, US 4,024,175 describe three methods to prepare Gabapentin. In U.S 4,024,175 1,1 Cyclopentanediacetic acid mono amide converted to Gabapentin hydrochloride salt by using sodium hypo bromide at 60°C for 2 hrs. Gabapentin hydrochloride salt converted to free Gabapentin by treatment with a basic ion exchange resin. All the methods proceed via the formation of acyl azide followed by rearrangement to isocyanate thereby resulting in the formation of Gabapentin hydrochloride salt, which is converted to free Gabapentin by treatment with a basic ion-exchange resin. The handling of acyl azide can be hazardous and the use of anion exchanger makes the process unattractive.

An improved process by Warner Lambart is described in US 5,319,135. This process involves the synthesis of intermediate 2-azaspiro [4.5] decane-3-one also known as Gabalactam. Subsequently, the Gabalactam was hydrolyzed in aqueous hydrochloric acid and neutralized by anion exchanger (OH form). The conversion of intermediates to the final product is a tedious process and the use of anion exchanger makes the process unattractive.

Another high yielding process for preparation of Gabapentin is disclosed in US 5,091,567, which involves Wittig-Horner reaction on cyclohexanone followed by Michael addition of nitromethane subsequently forming a mixture of Gabalactam and Gabapentin. The mixture thus obtained was passed through a column of anion exchanger (OH form). But the process as set out in US 5,091,567 involves the use of potentially hazardous nitromethane which renders the process unfavorable for manufacturing.

Certain methods for the preparation of Gabapentin was disclosed in US patent applications US 2002/0061931 and US 2002/0045662 wherein, Gabapentin HCl was dissolved in dry isopropanol and activated carbon was added. The suspension was heated and washed with isopropanol followed by addition of tributylamine thus causing the formation of Gabapentin base which was further separated from the suspension by filtration and washed with methanol. The said method involved the use of potentially toxic tributylamine thus makes the process unfavourable for manufacturing.

Another process as disclosed in US 2005/0148792 that involves alkylation of imine derived from cyclohexane carboxaldehyde followed by reductive amination of resulting intermediate to lactam followed by acidic hydrolysis to give Gabapentin in three steps. Due to the high cost and very poor overall yield this process cannot be commercialized.

In US patent application US 2005/0119503 another process was claimed which describes the conversion of Gabapentin hydrochloride to free base and then to its sulphate salt which is further treated with an inorganic base to obtain free Gabapentin. The patent also describes the use of barium hydroxide as one of the inorganic bases which converts sulphate salt to free Gabapentin. The process is cumbersome and involves a number of steps. Further use of barium hydroxide introduces toxic barium ions into the product at the final stages and requires extensive purification steps.

US Patent 2006/0149099 also describe a similar process, but the process involves the heating of reaction mixture to 50-90° C., preferably at 60-70° C. This results in the formation of lactam to a significant extent. Gabapentin obtained by these methods show high amounts of chloride, which is mainly from sodium chloride formed during neutralization with sodium hydroxide. This method involves extensive purification steps to remove the chlorides.

In US2008/0103334 A1 1,1 Cyclopentane diacetic acid mono amide converted to Gabapentin HCl salt by using sodium hypobromide at 35-40°C for 2 hrs. Gabapentin HCl converted to Gabapentin by using organic bases (Tri ethyl amine) and final yield is very low and makes the process unfavourable for manufacturing.

Therefore to overcome the shortcomings in the process of preparation of Gabapentin known from the prior art, there is a need to develop an improved and efficient process for the preparation of Gabapentin of formula (I) with higher yield of 72% and higher chemical purity under more favourable conditions and which is readily amenable to scale-up.

Objectives of the Invention
An object of the present invention is to provide a process for the preparation of a compound of formula (I), which is simple, economical, user- friendly and commercially viable.

Summary of the Invention
Accordingly, the present invention provides an improved process for the preparation of compound of formula (I), which comprises the steps of:
A) Preparation of Gabapentin hydrochloride
i) Reacting 2-(1-(2-amino-2-oxoethyl) cyclohexyl)acetic acid with a phase transfer catalyst in presence of alkali hypohalide reagent;
ii) Suitably extracting and processing the intermediate of step (i) to obtain Gabapentin hydrochloride.

B) Preparation of Gabapentin of formula (I) from Gabapentin Hydrochloride
i) Dissolving Gabapentin hydrochloride in suitable solvent followed by maintaining it at an appropriate temperature;
ii) Purification and recovery of the residue of step (i) to obtain pure Gabapentin of formula I.

Detailed Description of the Invention
A) Preparation of Gabapentin hydrochloride:
i) Reacting 2-(1-(2-amino-2-oxoethyl)cyclohexyl)acetic acid with a phase transfer catalyst in presence of alkali hypohalide reagent;
ii) Suitably extracting and processing the intermediate of step (i) to obtain Gabapentin hydrochloride.
B) Preparation of Gabapentin of formula (I) from Gabapentin Hydrochloride:
i) Dissolving Gabapentin hydrochloride in suitable solvent followed by maintaining it at an appropriate temperature;
ii) Purification and recovery of the residue of step (i) to obtain pure Gabapentin of formula I.

Accordingly in present invention, the 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid may be reacted in step (i) with a phase transfer catalyst. The phase transfer catalyst may preferably be selected from the group comprising trioctyl methyl ammonium bromide, benzyl triethyl ammonium bromide or chloride, hexyl triethyl ammonium bromide, hexadienyl triethyl ammonium bromide, dodecyl triethyl ammonium bromide, tridodecyl methyl ammonium chloride, didodecyl dimethyl ammonium chloride, trimethyl dodecyl ammonium chloride, tri dodecyl pentyl ammonium bromide, trihexyl hexadecyl ammonium bromide, tridodecyl benzyl ammonium chloride, trimethyl benzyl ammonium chloride, tetrabutyl phophonium chloride, trioctyl ethyl phosphonium bromide, triethyl hexadecyl phosphonium bromide, tributyl decyl phosphonium bromide, tetraphenyl phosphonium bromide and chloride and tetraphenyl arsosium chloride. More preferably the phase transfer catalyst is Tetrabutyl ammonium hydrogen sulphate.

The alkali hypohalide reagent of step (i) may be prepared by dissolving Caustic soda lye or sodium hydroxide in water followed by addition of bromine at an appropriate temperature. The bromine may be added at an appropriate temperature range between -5°C to 3°C, more preferably at -3°C to 3 °C and most preferably at temperature range between -3°C to 0°C. The reaction may preferably maintained at temperature range between -5°C to 3°C more preferably at -3°c to 0°C.

The alkali hypohalide reagent of step (i) may be added in presence of an organic solvent wherein the solvent may be selected from the group comprising chloroform, methyl isobutyl ketone, methylene dichloride, carbon tetrachloride, EDC, ethyl acetate, diisopropyl ether, toluene, xylene, diethyl ether, more preferably the solvent is methylene dichloride.

The reaction may further optionally be maintained at a temperature range of about 20°C to 50°C for 1 to 5 hours, more preferably at 25°C to 45°C for 1 to 3 hours and most preferably at temperature range between 30°C to 40°C for 1 to 2 hours.

The reaction mixture of step (i) may optionally be added in presence of an organic solvent in step (ii) followed by separation of organic layer from aqueous layer after completion of reaction. The organic solvent may preferably be selected from the group comprising chloroform, methyl isobutyl ketone, methylene dichloride, carbon tetrachloride, ethylene dichloride, ethyl acetate, di-isopropyl ether, toluene, xylene, diethyl ether, more preferably the organic solvent is methylene dichloride.

The aqueous layer may further optionally be cooled to a temperature range of about 5°C to 10°C followed by acidification with hydrochloric acid to form an acidic layer. The pH of the acidic layer may range between pH 4.0 to 5.5, more preferably pH 4.5 to 5.5 and most preferably pH 4.8 to 5.2.

The acidic layer may further be washed with an organic solvent followed by separation of aqueous layer, wherein the organic solvent may preferably be selected from the group comprising chloroform, methyl isobutyl ketone, methylene dichloride, carbon tetrachloride, ethylene dichloride, ethyl acetate, di-isopropyl ether, toluene, xylene, diethyl ether, more preferably the organic solvent is methylene dichloride or ethyl acetate which may be used individually or in combination with vacuum salt, more preferably the solvent is used in combination with vacuum salt.

The pH of the reaction mixture may preferably range between pH 1.0 to 2.0, more preferably the pH is 1.0 to 1.5.

Preparation of Gabapentin from Gabapentin hydrochloride
The Gabapentin hydrochloride thus obtained may be solubilised in a suitable solvent at step (i) followed by maintaining the reaction mixture at an appropriate temperature. The solvent may preferably be selected from the group comprising demineralised water, methyl alcohol, ethyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, tertiary butyl alcohol, and the like or combination thereof with demineralised water. More preferably the solvent for solubilising is demineralised water.

The solubilisation may be carried out at a temperature range between 35°C to 55°C, more preferably 40°C to 50°C and most preferably 45°C to 50°C. Following solubilisation, the pH of the reaction mixture may be adjusted in range of pH 7.5 to 8.5, more preferably the pH 8.0 to 8.5. The reaction mixture may further be allowed to cool at a temperature range between 0°C to 5°C.

The reaction mixture may further optionally be maintained for a time period of 1 to 3 hours, more preferably for 1 to 2 hours followed by filtration to obtain a solid mass. The filtered mass may preferably be purified in step (ii) by washing it with an organic solvent followed by filtration, purification and recovery to obtain the pure Gabapentin of the present invention.

The said organic solvent used for washing may preferably be selected from the group comprising water, methyl alcohol, ethyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, tertiary butyl alcohol, acetone, ethyl acetate, and the like or combination of above solvents, more preferably the solvents used are acetone and water and is used in combination.

Not being limited by the theory, the present invention provides a novel and efficient process for the preparation of Gabapentin of formula I. The process of the present invention involves the use of phase transfer catalyst which improves the yield of the final product. The use of phase transfer catalyst further stabilizes the alkali hypohalide reagent by converting the hypohalide in situ. The process of the present invention demonstrates the use of immiscible organic solvents which removes the lactam and other process related impurities.

In an aspect of the present invention, usage of phase transfer catalysts found to be very advantageous as the Ionic reactants are often soluble in an aqueous phase but insoluble in an organic phase in the absence of the phase-transfer catalyst. By using a PTC, the reaction rate and solubility’s found to be very impressive in yield wise as its control over maximum conversion of the reactants and obtain higher yields, make fewer by-products, eliminate the need for expensive or dangerous solvents that will dissolve all the reactants in one phase, eliminate the need for expensive raw materials and/or minimize waste problems.

Advantages
1) A process for the preparation of GABAPENTINE using phase transfer catalyst and alkali hypo halide solution in an alkaline water media.
2) Effective elimination of Lactam impurity and associated impurities with simple ethyl acetate washings at pH 4.8 to 5.2 in preparation of Gabapentin hydrochloride.
3) In our claimed process (to avoid the volatile impurities), we are preparing Gabapentin from Gabapentine HCl in aqueous medium using inorganic base where as in other methods required of organic bases, acidic and basic resins and alcoholic solvents were used for the purifications.
4) In precise, invention of this process will provide environmentally less polluting, high purity & high chemical yield of the final pharmaceutically active product leading to a low cost of production.

The invention is now described in detail with reference to the following examples; however, the following examples should not be construed as limiting the scope of the present invention in any way.

Examples
Example 1: Preparation of alkali hypohalide solution:
Dissolve Caustic soda lye (78.14g; 1.953 moles) as 100 % in DM water (263 mL) at an ambient temperature and cool the mass to 00C. Add bromine (81 g; 0.506 moles) to the alkali solution at temperature of below 30C and stir for 30 minutes.

Example 2: Preparation of Gabapentin hydrochloride using PTC:
Dissolve Caustic soda lye (78.14 g; 1.953 moles) as 100% in DM water (263 mL) at an ambient temperature followed by addition of 2-(1-(2-amino-2-oxoethyl)cyclohexyl) acetic acid (100 g; 0.502 moles). The reaction mixture is stirred for time period of 30 minutes at 30 to 400 C to get clear solution followed by addition of 1% Tetra butyl ammonium hydrogen sulfate. Add methylene dichloride (165 mL) and NaOBr solution to reaction mass for 2 to 3 hrs at 30 to 400C. The reaction is maintained for 1 hr at 30 to 400C followed by separating the aqueous and organic layer. The aqueous layer further cooled to a temperature of 0 to 50C, followed by acidification using Hydrochloric acid (280 mL) at below 150C. The pH should be in between 4.8 to 5.2; otherwise adjust pH with HCl or Caustic soda lye. Add methylene dichloride (165 mL) and add Vacuum salt (100 g) stir, settle and separate the layers. The aqueous layer is washed with methylene dichloride (165 mL) followed by addition of Vacuum salt 13 g and the aqueous layer was again separated, add ethyl acetate (300 mL) and adjust pH with HCl to 1.0 to 1.5 at below100C and cool the reaction mass temperature to 0 to -100C. Settle and separate the bottom aqueous layer. Stir for 15 to 20 minutes at 0 to -100C and filter the mass and wash with ethyl acetate 150 mL. Subject wet material to purification with ethyl acetate and water at 40 to 45oC, and air dry the material for 3 hrs to yield pure Gabapentin hydrochloride (semi dried), 100 g (95.9%).

Example 2a: Preparation of Gabapentin
Dissolve Gabapentin hydrochloride (100 g; 0.481 moles) in DM water (200 mL) at 45 to 50oC. Adjust the pH to 8.0 to 8.5 with 48 % caustic soda lye and maintain for 30 minutes. Cool to below 50C, maintain for 2 hours and filter the material. Wash the cake with acetone & water mixture. Subject wet material to purification in 20% acetone water mixture (300 mL) to yield pure Gabapentin (63 g, 75.1 %). The overall yield of Gabapentin starting from 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid is about 72%.

Example 3: Preparation of Gabapentin hydrochloride without PTC.
Dissolve Caustic soda lye (78.14 g; 1.953 moles) as 100% in DM water (263 mL) at an ambient temperature and add 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid (100 g; 0.502 moles) below 400C. Stir for 30 minutes at 30 to 400 C to get clear solution. Add methylene dichloride (165 mL) and slowly feed NaOBr solution to reaction mass for 2 to 3 hrs at 30 to 400C. Maintain for 1 hr at 30 to 400C. Settle the reaction mass and separate the bottom methylene dichloride layer. Cool the top aqueous layer to 0 to 50C. Charge HCl (280 mL) in to another RBF and slowly quench the aqueous layer in 3 to 4 hrs below 150C and check the reaction mass pH. The pH should be in between 4.8 to 5.2; otherwise adjust pH with HCl or Caustic soda lye. Add methylene dichloride (165 mL) and add Vacuum salt (100 g), stir, settle and separate the layers. Take aqueous layer and wash with methylene dichloride (165 mL) and add Vacuum salt 13 g (here methylene dichloride washings are introduced to remove Lactum and other related impurities). Take aqueous layer, cool to 50C, charge ethyl acetate (300 mL) and adjust pH with HCl to 1.0 to 1.5 at below100C and cool the reaction mass temperature to 0 to -100C. Settle and separate the bottom aqueous layer. Stir for 15 to 20 minutes at 0 to -100C and filter the mass and wash with ethyl acetate 150 mL. Subject wet material to purification in ethyl acetate at 40 to 45oC, and air dry the material for 3 hrs to yield pure Gabapentin hydrochloride (semi dried), 85 g (81.5%).

Example 3a: Preparation of Gabapentin
Dissolve Gabapentin hydrochloride (85 g; 0.409 moles) in DM water (170 mL) at 45 to 50oC. Adjust the pH to 8.0 to 8.5 with 48 % caustic soda lye and maintain for 30 minutes. Cool to below 50C, maintain for 2 hours and filter the material. Wash the cake with acetone & water mixture. Subject wet material to purification in 20% acetone water mixture (255 mL) to yield pure Gabapentin (52 g, 70%). The overall yield of Gabapentin starting from 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid is about 60.5%.

Example-4: Preparation of Gabapentin hydrochloride with PTC
Dissolve Caustic soda lye (78.14 g; 1.953 moles) as 100% in DM water (263 mL) at an ambient temperature and add 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid (100 g; 0.502 moles) below 400C. Stir for 30 minutes at 30 to 400 C to get clear solution. Then add 1% Tetra butyl ammonium hydrogen sulfate to the mass. Slowly feed NaOBr solution to reaction mass for 2 to 3 hrs at 30 to 400C. Maintain for 1 hr at 30 to 400C. Cool the mass to 0 to 50C. Charge HCl (280 mL) in to another RBF and slowly quench the mass in 3 to 4 hrs below 150C and check the reaction mass pH. The pH should be in between 4.8 to 5.2; otherwise adjust pH with HCl or Caustic soda lye. Add ethyl acetate (165 mL) and add Vacuum salt (100 g), stir, settle and separate the layers. Take aqueous layer and add ethyl acetate (165 mL) and Vacuum salt (13g), stir, settle and separate the layers. Take aqueous layer, cool to 50C, charge ethyl acetate (300 mL) and adjust pH with HCl to 1.0 to 1.5 at below100C, and cool the reaction mass temperature to 0 to -100C. Settle and separate the bottom aqueous layer. Stir for 15 to 20 minutes at 0 to -100C and filter the mass and wash with ethyl acetate 150 mL. Subject wet material to purification in ethyl acetate and water at 40 to 45oC, and air dry the material for 3 hrs to yield pure Gabapentin hydrochloride (semi dried) 95 g (91%).

Example-4a: Preparation of Gabapentin
Dissolve Gabapentin hydrochloride (95 g; 0.457 moles) in DM water (190 mL) at 45 to 50oC. Adjust the pH to 8.0 to 8.5 with 48 % caustic soda lye and maintain for 30 minutes. Cool to below 50C, maintain for 2 hours and filter the material. Wash the cake with acetone & water mixture. Subject wet material to purification in 20% acetone water mixture (285 mL) to yield pure Gabapentin (57 g, 72.6 %). The overall yield of Gabapentin starting from 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid is about 66.3%.

Example-5: Preparation of Gabapentin hydrochloride without PTC
Dissolve Caustic soda lye (78.14 g; 1.953 moles) as 100% in DM water (263 mL) at an ambient temperature and add 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid (100 g; 0.502 moles) below 400C. Stir for 30 minutes at 30 to 400 C to get clear solution. Slowly feed NaOBr solution to reaction mass for 2 to 3 hrs at 30 to 400C. Maintain for 1 hr at 30 to 400C. Cool the mass to 0 to 50C. Charge HCl (280 mL) in to another RBF and slowly quench the mass in 3 to 4 hrs below 150C and check the reaction mass pH. The pH should be in between 4.8 to 5.2; otherwise adjust pH with HCl or Caustic soda lye. Add ethyl acetate (165 mL) and add Vacuum salt (100 g), stir, settle and separate the layers. Take aqueous layer and add ethyl acetate (165 mL) and Vacuum salt (13g), stir, settle and separate the layers. Take aqueous layer, cool to 50C, charge ethyl acetate (300 mL) and adjust pH with HCl to 1.0 to 1.5 at below100C and cool the reaction mass temperature to 0 to -100C. Settle and separate the bottom aqueous layer. Stir for 15 to 20 minutes at 0 to -100C and filter the mass and wash with ethyl acetate 150 mL. Subject wet material to purification in ethyl acetate and water at 40 to 45oC, and air dry the material for 3 hrs to yield pure Gabapentin hydrochloride (semi dried) 86 g (82.4%).

Example-5a: Preparation of Gabapentin
Dissolve Gabapentin hydrochloride (86 g; 0.414 moles) in DM water (172 mL) at 45 to 50oC. Adjust the pH to 8.0 to 8.5 with 48 % caustic soda lye and maintain for 30 minutes. Cool to below 50C, maintain for 2 hours and filter the material. Wash the cake with acetone & water mixture. Subject wet material to purification in 20% acetone water mixture (258 mL) to yield pure Gabapentin (52.2 g, 69.2%). The overall yield of Gabapentin starting from 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid is about 60%.

Example-6: Comparison of process of present invention with available process in prior art
Comparison of various gabapentin process available in prior art with process of present invention for distinguishing its simple, economical, user- friendly and commercially viable advantages on the basis of percentage yield and other process variables used for the manufacturing of gabapentin is presented here below at Table 6a.
Table 6a & Table 6b: Comparison of process of present invention with available process in prior art

Table 6a: Yield and disadvantages of process available process in prior art
S.No Patent no Yield Disadvantages
1 US 4,024,175 Not given Lactam (a major impurity) inevitably forms to a significant extent. Use of Ion exchange resin for purification makes the process very expensive.
2 US 5,319,135 56% Lactum converted to gaba hydrochloride take a long hrs at Reflux temp also used Ion- exchange resins makes the process very expensive.
3 US2002/0061931 72% (Gabapentin HCl to Gabapentine preparation only). Use of toxic tributyl amine makes the process unfavourable for scale ups.
4 US2005/0119503 80% Number of steps used.
Use of barium hydroxide introduces toxic barium ions into the product at the final stages and requires extensive purification steps makes the process very expensive.
5 US2008/0103334 A1 58% The claimed method involved the use of tri ethyl amine but yields is very low thus makes the process unfavourable for manufacturing.
6 SARACA PROCESS 72% Elimination of lactam formation during the experiment and purification with simple acetone water mixture makes the process simple, economical, user- friendly and commercially viable.

Table 6b: Yield and advantages of process of present invention
S.No Yield Advantages
1 72% Elimination of lactam impurities of prior art and purification with simple acetone water mixture makes the process simple, economical, user- friendly and commercially viable.

INFERENCE: From Table 6a and 6b it may be noted that the product obtained by the process of present invention is yielding gabapentin product which is highly economical, user- friendly and commercially viable with overall process yield of more than 72%. Thus above tables clearly indicate that the gabapentin produced from the process of present invention is much more pure, economical, user- friendly and commercially viable and solve the problem present in prior art. ,CLAIMS:WE CLAIM:
1.A process for the preparation of 1-(aminomethyl)cyclohexaneacetic acid of formula formula (1), comprising steps of:

Formula (1)

A) preparation of Gabapentin hydrochloride
i) reacting 2-(1-(2-amino-2-oxoethyl) cyclohexyl) acetic acid with a phase transfer catalyst in presence of alkali hypohalide reagent;
ii) suitably extracting and processing the intermediate of step (i) to obtain Gabapentin hydrochloride.

B) preparation of Gabapentin of formula (I) from Gabapentin Hydrochloride
i) dissolving Gabapentin hydrochloride in suitable solvent followed by maintaining it at an appropriate temperature;
ii) purification and recovery of the residue of step (i) to obtain pure Gabapentin of formula I.

2.The process as claimed in step (A) of claim 1, wherein the phase transfer catalyst is selected from the group comprising trioctyl methyl ammonium bromide, benzyl triethyl ammonium bromide or chloride, hexyl triethyl ammonium bromide, hexadienyl triethyl ammonium bromide, dodecyl triethyl ammonium bromide, tridodecyl methyl ammonium chloride, didodecyl dimethyl ammonium chloride, trimethyl dodecyl ammonium chloride, tri dodecyl pentyl ammonium bromide, trihexyl hexadecyl ammonium bromide, tridodecyl benzyl ammonium chloride, trimethyl benzyl ammonium chloride, tetrabutyl phophonium chloride, trioctyl ethyl phosphonium bromide, triethyl hexadecyl phosphonium bromide, tributyl decyl phosphonium bromide, tetraphenyl phosphonium bromide and chloride and tetraphenyl arsosium chloride, preferably the phase transfer catalyst is tetrabutyl ammonium hydrogen sulphate.
3.The process as claimed in step (A) of claim 1, wherein the alkali hypohalide reagent is prepared by dissolving Caustic soda lye in water followed by addition of bromine at an temperature range from -5°C to 3°C,preferably at -3°C to 3 °C and more preferably at temperature range from -3°C to 0°C.

4.The process as claimed in step (A) of claim 1, wherein the alkali hypohalide reagent of step (i) is added in presence of an organic solvent;
wherein the organic solvent is selected from the group comprising chloroform, methyl isobutyl ketone, methylene dichloride, carbon tetrachloride, EDC, ethyl acetate, diisopropyl ether, toluene, xylene, diethyl ether, preferably the solvent is methylene dichloride.

5.The process as claimed in step (A) of claim 1, wherein the reaction is further maintained at a temperature range from 20°C to 50°C for 1 to 5 hours, preferably at 25°C to 45°C for 1 to 3 hours and more preferably at temperature range between 30°C to 40°C for 1 to 2 hours.

6.The process as claimed in step (A) of claim 1, wherein the reaction mixture of step (i) is added in presence of an organic solvent in step (ii) followed by separation of organic layer from aqueous layer after completion of reaction;
wherein the reaction mixture is maintained at pH range from pH 1.0 to 2.0, preferably pH in the range from 1.0 to 1.5;
wherein the organic solvent is selected from the group comprising chloroform, methyl isobutyl ketone, methylene dichloride, carbon tetrachloride, ethylene dichloride, ethyl acetate, di-isopropyl ether, toluene, xylene, diethyl ether, preferably the organic solvent is methylene dichloride;
wherein the aqueous layer is further cooled to a temperature range from 5°C to 10°C followed by acidification with hydrochloric acid to form an acidic layer at a pH range from pH 4.0 to 5.5, preferably pH 4.5 to 5.5 and more preferably pH 4.8 to 5.2;
wherein the acidic layer is washed with an organic solvent followed by separation of aqueous layer;
wherein the organic solvent is selected from the group comprising chloroform, methyl isobutyl ketone, methylene dichloride, carbon tetrachloride, ethylene dichloride, ethyl acetate, di-isopropyl ether, toluene, xylene, diethyl ether, preferably the organic solvent is methylene dichloride or ethyl acetate;
wherein organic solvent is used individually or in combination with vacuum salt, preferably the organic solvent is used in combination with vacuum salt.

7.The process as claimed in step (B) of claim 1, wherein the gabapentin hydrochloride is solubilised in a solvent at step (i) followed by maintaining the reaction mixture at an temperature range from 35°C to 55°C, preferably 40°C to 50°C and more preferably 45°C to 50°C;
wherein the solvent is selected from the group comprising demineralised water, methyl alcohol, ethyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, tertiary butyl alcohol, and the like or combination thereof, preferably the solvent is demineralised water;
wherein the gabapentin hydrochloride is solubilised at a pH range from 7.5 to 8.5, preferably the pH is 8.0 to 8.5;
wherein the reaction mixture is further allowed to cool at a temperature range from 0°C to 5°C;
wherein the reaction mixture is further maintained for a time period of 1 to 3 hours, preferably for 1 to 2 hours followed by filtration to obtain a residue in the form of solid mass.

8.The process as claimed in step (B) of claim 1, wherein the residue recovered from step (i) is further purified in step (ii) by washing with an organic solvent followed by filtration, purification to obtain the pure Gabapentin of formula 1;
wherein the organic solvent is selected from the group comprising water, methyl alcohol, ethyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, tertiary butyl alcohol, acetone, ethyl acetate, and the like or combination thereof, preferably the solvent used in combination of acetone and water.