| 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/BaSO_4 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......
I Was asking the elders here any new thoughts on this /? It's been goin on 60 yrs and in the last decade this and another synth have
made great progress when they thought it could not be improved on.This is Aug 2012.Gaik b. Kok and Peter J. Scammells |
