PROCESS FOR THE PREPARATION OF METHYLPHENIDATE AND PHARMACEUTICAL SALTS THEREOF

摘要

The present invention is directed to an improved process for the preparation of methylphenidate, stereoisomer, mixture of stereoisomers and pharmaceutically acceptable salts thereof, more particularly, the sulfate and hydrochloride salts of methylphenidate, di-threo-methylphenidate and dex-methylphenidate. Methods of removing or reducing the amount of impurities from the above described process are also disclosed.

主权项

1. A process for the recrystallization of di-threo-methylphenidate hydrochloride;
wherein the recrystallized di-threo-methylphenidate hydrochloride comprises a total of less than about 0.1 area % of an impurity compound selected from the group consisting of an impurity compound of formula (IMP-5) an impurity compound of formula (IMP-6) an impurity compound of formula (IMP-15) an impurity compound of formula (IMP-16) and mixtures thereof; comprising the steps of (a) dissolving di-threo-methylphenidate hydrochloride in a mixture of an organic solvent and water; wherein the organic solvent is selected from the group consisting of ethanol and isopropanol; and wherein the water is present in an amount in the range of from about 0.1 wt/wt equiv. to about 0.6 wt/wt equiv.; (b) heating the mixture to about reflux temperature; (c) optionally distilling off between about 20% and about 65% by volume of the mixture of an organic solvent and water; (c) cooling the mixture to a temperature less than about room temperature; and (d) isolating the di-threo-methylphenidate as a solid.