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PubMed · 994146

Conversion of Thebaine to Codeine.

R B Barber·H Rapoport
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Abstract

An improved conversion of thebaine to codeine has been developed. Oxymercuration of thebaine with mercuric acetate in refluxing methanol, followed by hydrolysis of the intermediate 7-acetomercurineopinone dimethyl ketal with 3 N acetic acid, or, alternatively, reduction of the organomercury compound with sodium borohydride and mild acid hydrolysis of the resulting neopinone dimethyl ketal, gives neopinone in 95-100% yields. Either acid- or alkali-catalyzed isomerization to codeinone leads to the equilibrium mixture consisting of codeinone-neopinone, 3:1. Complete conversion to codeinone in 85-90% yield results from treatment of neopinone with anhydrous hydrogen chloride or hydrogen bromide in ether-methylene chloride, followed by elimination of hydrogen halide from the intermediate 8-halodihydrocodeinone. The known borohydride reduction of codeinone then gives codeine in 85% overall yield from thebaine.

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CodeineDealkylationMagnetic Resonance SpectroscopyMolecular ConformationOxidation-ReductionThebaineJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.

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R B Barber, H Rapoport. 1976. Conversion of Thebaine to Codeine.. https://doi.org/10.1021/jm00232a002

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