Sequential benzylic oxidations of the naloxone ring system

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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546 45, 546 46, C07D48902

Patent

active

061662119

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.

REFERENCES:
Archer, S. et al. : 10-Ketonaltrexone and 10-Ketooxymorphone. J. Med. Chem. vol. 28, pp. 974-976, 1985.
Sagara, T. et al. : Design and synthesis of 10-oxo derivative of N-cyclopropylmethyl (-)-6-beta-acetylthiodihydronormorphine. Bioorganic & Medicinal Chem. Lett. vol. 5, pp. 1505-1508, 1995.

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