Patent ID: 7002016
Filing Date: 2006-02-21
Classification: A61K,C07D

Abstract:
1. A process for the preparation of threo-methylphenidate hydrochloride comprising: contacting 1-(phenylglyoxylyl)piperidine arenesulfonylhydrazone of the formula wherein Ar denotes an aryl group, where the aryl group may be substituted by a C 1 –C 6 alkyl, halo or nitro group; with an inorganic base in the presence of a water immiscible organic solvent and a phase transfer catalyst to obtain (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one of the formula: wherein said phase transfer catalyst is trioctylmethylammnonium chloride, (i) reacting the (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one with a solution of hydrogen chloride in methanol to obtain threo-enriched methylphenidate hydrochloride; (ii) crystallizing the threo-enriched methylphenidate hydrochloride prepared in step (i) to give the hydrochloride salt of threo-methylphenidate containing 98.8% of the erythro-isomer.