Method of producing thebaine from codeine and oripavine from morphine

US4045440A · kind A · utility

Assignee

• The United States of America as represented by the Department of Health, Education and Welfare · US

Inventors

• Henry Rapoport · Berkeley, US
• Randy B. Barber · Berkeley, US

Key dates

• Filing date: Sep 16, 1976
• Grant date: Aug 30, 1977
• Expiry date: Sep 16, 1996

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D489/02
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A method of producing thebaine from codeine and oripavine from morphine which comprises (a) producing the 0-6 methyl ethers from codeine and morphine using potassium hydride and methyl iodide as the O-alkylation agents and (b) subsequently oxidizing the respective 0-6 methyl ethers of codeine and morphine to shift from allylic structure to a dienol ether structure using an oxidizing amount of MnO.sub.2 in tetrahydrofuran to produce thebaine from codeine and oripavine from morphine. In the case of morphine, it is preferable to protect the 0-3 position by acetylation prior to the oxidizing step. Both the etherification and oxidizing steps are carried out under a protecting blanket such as nitrogen and the reactions are carried out preferably under atmospheric pressure and ambient temperature with the exception of the etherification affecting the 0-6 position which may be commenced by cooling with ice.