Benzophenone → Hydrocodone

Participants

Reaction Steps

Benzophenone (6.22 g), cyclohexane (22 mL), dried codeine (1.38 g) and chlorotris(triphenylphosphine)rhodium (I) (Wilkinson's catalyst) (0.22 g) were charged into a glass hydrogenation bottle. The bottle was evacuated and filled with hydrogen. The mixture was magnetically agitated at ambient temperature (24–28° C.) while the hydrogen pressure was maintained at 5–15 psi until the pressure drop caused by the hydrogen consumption stopped. A solution of potassium tert-amylate in cyclohexane (12 mL, 15.4% w/w) was charged into the bottle with the reaction mixture in one portion, the mixture was magnetically agitated under nitrogen at ambient temperature for 4 hours and quenched by adding 1.5N acetic acid (13 mL) to the solution with mixing and cooling in an ice bath. Alternatively, in another embodiment the solution may be quenched by adding the solution to 1.5N acetic acid with mixing and cooling in an ice bath. The mixture was filtered, aqueous layer was separated and the organic layer was extracted with 1.5N acetic acid (2 mL). Combined aqueous layer (14.5 mL) according to the assay by HPLC contains 89.7 mg/mL hydrocodone (94% yield), purity 95 area %.

Provenance & Evidence