Direct synthesis of naltrexone by palladium-catalyzed N-demethylation/ acylation of oxymorphone: The benefit of C-H activation and the intramolecular acyl transfer from C-14 hydroxy

Abstract

Oxymorphone was converted to naltrexone in three steps by palladium-catalyzed oxidative N-demethylation and intramolecular acyl transfer from C-14 hydroxy to N-17. Vitride TM reduction of N-acylamide to N-alkylamine proceeded with concomitant reductive deprotection of C-6 and O-3 functionalities. © 2012 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.