Process of lactonization in the preparation of statins

US5917058A · kind A · utility

Assignee

• RANBAXY LABORATORIES LIMITED · IN

Inventors

• Yatendra Kumar · Barwala, IN
• Rajesh Kumar Thaper · Jammu, IN
• S. M. Dileep Kumar · New Delhi, IN
• Jag Mohan Khanna · New Delhi, IN

Key dates

• Filing date: Apr 22, 1998
• Grant date: Jun 29, 1999
• Expiry date: Apr 22, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D309/30
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

An improved process of lactonization in the preparation of statins (e.g., the HMG--CoA reductase inhibitors lovastatin and simvastatin) employs very mild reaction conditions. The improved process comprises treating the open ring hydroxy acid form of the statins with an excess of acetic acid and in the absence of a strong acid catalyst under mild heating conditions (e.g., ambient to 55.degree. C.), and adding an anti-solvent to the reaction mixture, thereby causing the statins in lactone form to crystalize from the reaction mixture. The acetic acid serves as both a solvent and a catalyst for the lactonization reaction.