Improved synthesis of 14-hydroxy opioid pharmaceuticals and intermediates

Gaik Beng Orbell, Peter John Scammells

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Significantly improved reaction conditions for the synthesis of oxycodone (1), via the conventional two-step process involving oxidation of thebaine (3) into 14-hydroxycodeinone (5) and the subsequent reduction of 5 via catalytic hydrogenation, are reported. Employing the hydrochloride salt of thebaine (3) in the oxidation step, in place of the more traditionally used free base form of this opiate, now provides 5 in high yield and purity. For the reduction step, aqueous acetic acid has typically been employed as the solvent. However, this was found to generate varying amounts of 14-hydroxydihydrocodeine (16) as the dominant by-product. Instead, using 5 Pd/BaSO4 as the catalyst and MeOH as the solvent completely eliminated the formation of 16, giving oxycodone (1) in high yield and purity, without the need to purify the intermediates. These improved conditions have also proved effective in the synthesis of other 14-hydroxyopiates, such as oxymorphone (2) and N-noroxymorphone (9). In the latter case, a high overall yield was achieved by starting from N-nororipavine (10), without the need to employ protecting groups.
Original languageEnglish
Pages (from-to)11318 - 11325
Number of pages8
JournalRSC Advances
Volume2
Issue number30
DOIs
Publication statusPublished - 2012

Cite this