Preparation of quinuclidine-3-methanol

US4925942A · kind A · utility

Assignee

• Rutgerswerke Aktiengesellschaft · DE

Inventors

• Josef Gotz · Heidelberg, DE
• Winfried Orth
• Wolfgang Weiss · Ottobrunn, DE
• Bernd Rapp · Ketsch, DE
• Hans W. Kleffner · Battenberg, DE

Key dates

• Filing date: Jul 24, 1989
• Grant date: May 15, 1990
• Expiry date: Jul 24, 2009

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D453/02
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A process for the preparation of quinuclidine-3-methanol comprising reacting quinuclidine-3-one acid addition salt with an alkali metal cyanide in an aqueous media to obtain 3-cyano-3-hydroxy-quinuclidine, reacting the latter with anhydrous methanol in the presence of hydrogen chloride gas followed by treatment with aqueous alkali to obtain methyl 3-hydroxy-quinuclidine-3-carboxylate, reacting the latter with thionyl chloride to form methyl 1-azabicyclo(2,2,2)oct-2-ene-3-carboxylate, hydrogenating the latter with Raney nickel to obtain methyl 1-azabicyclo(2,2,2)octane-3-carboxylate and reducing the latter to obtain quinuclidine-3-methanol which is an intermediate for mequitazine which is useful as an antihistaminic.