Method for selective acylation of C-2'-O-protected-10-hydroxy-taxol at the C-10 position

US6048990A · kind A · utility

Assignee

• NaPro BioTherapeutics, Inc. · US

Inventors

• Xian Liang · Moorestown, US
• Jan Zygmunt · Longmont, US
• Nicholas J. Sisti · Jeffersonville, US
• Madhavi C. Chander · Rosemont, US
• Herbert R. Brinkman · Superior, US
• James D. McChesney · Etta, US

Key dates

• Filing date: May 1, 1998
• Grant date: Apr 11, 2000
• Expiry date: May 1, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D305/14
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A method of acylating C-2' O-protected-10-hydroxy taxol selectively at the C-10 hydroxyl position over the C-7 hydroxy position thereof to produce C-2' O-protected taxol is accomplished first by dissolving C-2' O-protected-10-hydroxy taxol in an acceptable ether solvent therefor, such as tetrahydrofuran. A lithium salt, preferably lithium chloride, is added. A trialkylamine base or pyridine is next added, followed by the addition of an acylating agent, such as acetyl chloride. The resulting solution may be quenched, for example with ammonium chloride, to eliminate excess of the acylating agent. This solution may then be diluted with ethyl acetate to form an organic phase and an aqueous phase, with the organic phase being washed and thereafter reduced. Recrystallization and column chromatography may be employed to purify the C-2' O-protected taxol.