An efficient synthesis of 14β-aminocodeinone from thebaine

Abstract

Oxidation of 2,2,2-trichloroethyl N-hydroxycarbamate with sodium periodate in the presence of thebaine (1) gave (82%) a cycloadduct (4) of trichloroethyl nitrosoformate and the alkaloid. This adduct was converted with hydrogen chloride in ethylene glycol into 14β-N-(2,2,2-trichloroethoxycarbonyl)-N-hydroxyaminocodeinone ethylene acetal (5) and thence, via 14β-aminocodeinone ethylene acetal (6), into 14β-aminocodeinone (3) in an overall yield of 67–70%. Treatment of the adduct (4) with methanolic hydrogen chloride gave an equilibrium mixture (ca. 1 : 1) of (4) and the dimethyl acetal (2d) corresponding to (5).