Patent ID: 7247730

Claim:
A process for the preparation of dexmethylphenidate hydrochloride having high optical purity wherein said threo-N-Broc-ritalinic acid is prepared by a process comprising: (1) reacting a solution of threo-N-Boc-ritalinic acid with (S)-1-phenylethylamine, separating precipitated salt of (R,R)-enriched N-Boc-ritalinic acid with (S)-1-phenylethylamine from the reaction mixture and recrystallizing, reslurrying and/or trituring of said salt in crystalline form; (2) mixing the solid salt of (R,R)-N-Boc-ritalinic acid and (S)-1-phenylethylamine, obtained in step (1) with aqueous acid and separating (R,R)-N-Boc-ritalinic acid from the mixture; (3) deprotecting and esterifying the (R,R)-N-Boc-ritalinic acid prepared in step (2) to give dexmethylphenidate hydrochloride with optical purity of at least 99% ee; (4) contacting a solution of 1-(phenylglyoxylyl)piperidine arenesulfonylhydrazone of the formula wherein Ar is an aryl group, in a water immiscible organic solvent, with an inorganic base, in the presence of phase transfer catalyst to obtain 7-phenyl-1-azabicyclo[4.2.0]octan-8-one; (5) reacting the 7-phenyl-1-azabicyclo[4.2.0]octan-8-one of the formula: obtained in step (4) with a solution of hydrogen chloride in methanol to give methylphenidate; (6) reacting the methylphenidate prepared in step (5) with di-tert-butyl dicarbonate to give N-Boc-methylphenidate; (7) reacting N-Boc-methylphenidate with sodium hydroxide in an alcohol solution or aqueous alcohol solution and separating precipitated solid sodium salt of threo-N-Boc-ritalinic acid from the reaction mixture; (8) mixing the salt obtained in step (7) with an aqueous acid and separating threo-N-Boc-ritalinic acid from the obtained mixture.