Method for preparing 4-(6-amino-purin-9-YL)-2(S)-hydroxy-butyric acid methyl ester

US8247549B2 · kind B2 · utility

Assignee

• SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES · CN

Inventors

• Fajun Nan · Shanghai, CN
• Jianping Zuo · Shanghai, CN
• Yangming Zhang · Shanghai, CN
• Min Gu · Tangxia, CN
• Wei Tang · Shanghai, CN

Key dates

• Filing date: Nov 6, 2008
• Grant date: Aug 21, 2012
• Expiry date: Nov 6, 2028

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention discloses a novel method for preparing and purifying 4-(6-Amino-purin-9-yl)-2(S)-hydroxy-butyric acid methyl ester. The preparation started from cheap and easily available L-malic acid, which was transformed to intermediate I after simultaneous protection of the groups of 1-carboxyl and 2-hydroxyl. The intermediate I was selectively reduced to intermediate alcohol II, whose hydroxyl group was further transformed to an easily leaving group to afford intermediate III. The intermediate III was nucleophilically substituted with adenine to afford intermediate IV. The intermediate IV was deprotected and methyl-esterified simultaneously in methanol in the presence of an acid or a base to afford crude 4-(6-Amino-purin-9-yl)-2(S)-hydroxy-butyric acid methyl ester, which was purified by recrystallization to afford the purified product. Comparing with the prior preparation methods, the present method has advantages in low cost, mild conditions, high retention of the chiral center during the reaction, high productivity, great improvement in the quality and yield of the product and great decrease in cost, and thus is suitable for the production on a large scale.