The present invention provides an improved process for the preparation of a compound of formula (I), which comprises the steps of: formula (I), (a) reacting
isovaleraldehyde of formula (II) and
alkyl cyanoacetate of formula (III) optionally in presence of salts of weak acid and
weak base or
weak base in a suitable
solvent to get 2-cyano-5-methyl-hex-2-enoic acid
alkyl ester of formula (IV); (b) reacting 2-cyano-5-methyl-hex-2-enoic acid
alkyl ester of formula (IV) with a suitable
cyanide source in water or in an
organic solvent or mixture thereof to get 2-isobutylsuccinonitrile of formula (V); (c) obtaining optionally 2-isobutylsuccinonitrile of formula (V) by reacting
isovaleraldehyde of formula (II) and alkyl cyanoacetate of formula (III) in presence of suitable
cyanide source in water or in an
organic solvent or mixture thereof in
single step; (d) converting 2-isobutylsuccinonitrile of formula pa (V) to racemic 3-cyano-5-methyl-
hexanoic acid or salt thereof of formula (VI) with a genetically modified
nitrilase enzyme (Nit pt 9N_56_2) in water or optionally with an organic co-
solvent at appropriate pH and temperature; (e) converting racemic 3-cyano-5-methyl-
hexanoic acid or salt thereof of formula (VI) to racemic alkyl 3-cyano-5-methyl-hexanoate of formula (VII) by treatment with
alcohol (R3OH) and acidic catalyst or alkyl
halide (R3X) in presence of a base in a suitable
solvent or a mixture of solvents thereof; (f) obtaining (S)-alkyl 3-cyano-5-methyl-hexanoate of formula (VIII) and (R)-3-cyano-5-methyl-
hexanoic acid or salt thereof of formula (X) by enzymatic enantioselective
hydrolysis in water or
organic solvent or a mixture thereof from racemic alkyl 3-cyano-5-methyl-hexanoate of formula (VII); (g) obtaining optionally the compound of formula (VII) by racemizing unwanted (R)-3-cyano-5-methyl-hexanoic acid or salt thereof of formula (X) or substantially enriched (R)-3-cyano-5-methyl-hexanoic
acid salt thereof of formula (X) in presence of a base in organic solvent or a mixture thereof; (h) converting (S)-alkyl 3-cyano-5-methyl-hexanoate of formula (VIII) to
pregabalin of formula (I) by hydrolyzing ester group with suitable alkali or
alkaline earth metal base followed by hydrogenation optionally in one pot in a solvent selected from water or other organic solvents or a mixture thereof in presence of a suitable hydrogenation catalyst.