Process for the Preparation of Solifenacin and Salts Thereof

摘要

The invention provides a new process for the preparation of solifenacin or a pharmaceutically acceptable acid addition salt thereof, comprising reacting (R)-quinuclidin-3-yl phenethylcarbamate with benzaldehyde in the presence of an acid to obtain a diasteroisomeric mixture (S,R)—((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate of formula (IV) which can be resolved and the solifenacin or a pharmaceutically acceptable acid addition salt thereof recovered. The invention also provides the new key intermediate (R)-quinuclidin-3-yl phenethylcarbamate involved in the process. Further the invention provides a method for the transformation of (R)—((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate into a diasteroisomeric mixture (S,R)—((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate.

主权项

1. A process for preparing solifenacin or an acid addition salt thereof, comprising reacting (R)-quinuclidin-3-yl phenethylcarbamate of formula (III) with benzaldehyde: in the presence of an acid to obtain the diasteroisomeric mixture (S,R)—((R)-quinuclidin-3-yl) 1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate of formula (IV).