Industrial synthesis of tiotropium bromide

摘要

Preparation of tropenol (I) involves: (a) reducing a scopine ester (II) using zinc in presence of an activating metal salt; and (b) saponifying the product using base. Preparation of tropenol of formula (I) (or its acid addition salt) involves: (a) reducing a scopine ester of formula (II) (or its acid addition salt or hydrate) using zinc in presence of an activating metal salt (preferably an iron or copper salt) in a solvent; and (b) saponifying the product using base. [Image] R : 1-4C alkyl or phenyl-(1-4C) alkyl (both optionally substituted by OH or 1-4C alkoxy).