The Dupont Merck Pharmaceutical Company

Endo Pharmaceuticals Inc.

Spencer Drummond, Jr

George A Boswell

Gary Avonn Cain

Peter John Gillies

Jeffrey T Billheimer

James M Trzaskos

Indawati De Lucca

The present invention pertains to a process for the preparation of the 10-keto analogs of morphinan compounds. In the case of compounds having a 3-hydroxyl group, the 3-methyl ether protected analog is synthesized by selective phenolic methylation in the presence of the basic amino group. When nalbuphine, morphine, or codeine is used as the starting material, the additional 6-hydroxyl group is protected using acetylation. The protected analog is selectively oxidized by treatment with cerium ammonium nitrate to provide the 10-(S)-hydroxy adduct. The 10-(S)-hydroxy adduct is further oxidized to the 10-keto analog. Any protecting groups that were added prior to oxidation are cleaved subsequent to oxidation to form the desired 10-ketomorphinan.

Sequential benzylic oxidations of the naloxone ring system

Antihypercholesterolemic bis-trifluoromethyl-substituted imidazolines

Growing community of inventors

Wilmington, DE, United States of America

Spencer Drummond, Jr