Patent Number: 6,166,211

Title: Sequential benzylic oxidations of the naloxone ring system

Abstract: 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.

Inventors: Cain; Gary A. (Wilmington, DE), Drummond, Jr.; Spencer (Wilmington, DE)

Assignee: Endo Pharmaceuticals, Inc.

International Classification: C07D 489/02 (20060101); C07D 489/00 (20060101); C07D 489/08 (20060101); C07D 489/02 ()

Expiration Date: 12/26/2017