SYNTHESIS OF LEVOMETHADONE HYDROCHLORIDE OR DEXTROMETHADONE HYDROCHLORIDE AND METHODS FOR USE THEREOF

摘要

Highly efficient methods for synthesis of levomethadone hydrochloride or dextromethadone hydrochloride are provided starting from D-alanine, or L-alanine, respectively, with retention of configuration. Methods for treating a subject are provided comprising administering a composition comprising an effective amount of levomethadone hydrochloride having not more than 10 ppm dextromethadone.

主权项

1. A process for preparing levomethadone hydrochloride from D-alanine or dextromethadone hydrochloride from L-alanine, the process comprising:
converting D-alanine to N,N-dimethyl-D-alaninol or converting L-alanine to N,N-dimethyl-L-alaninol; combining the N,N-dimethyl-D-alaninol or the N,N-dimethyl-L-alaninol with an activating reagent to form a R-activated intermediate or an S-activated intermediate, respectively; mixing the R- or S-activated intermediate and a base with diphenylacetonitrile to provide levomethadone nitrile or dextromethadone nitrile, respectively; and exposing the levomethadone nitrile or dextromethadone nitrile to a Grignard reagent of formula RMgX, where R is ethyl and X=Cl, Br, or I, to form a reaction mixture; and adding hydrochloric acid to the reaction mixture to provide levomethadone hydrochloride or dextromethadone hydrochloride, respectively.