Benzophenone → Hydrocodone

Participants

Reaction Steps

Codeine (11.71 g), benzophenone (48.32 g), 5% palladium on carbon wet (67% water) catalyst (0.37 g), and cyclohexane (57 mL) were charged into a stainless steel autoclave. The autoclave was evacuated and filled with hydrogen. The mixture was mechanically agitated at ambient temperature (25–29° C.) while the hydrogen pressure was maintained at 19–38 psi until the pressure drop caused by the hydrogen consumption stopped. Cyclohexane (120 mL) was charged into the autoclave followed by solid potassium tert-butylate (16.22 g), the mixture was mechanically agitated under nitrogen at ambient temperature for overnight, and then quenched with 1.5N acetic acid (150 mL) with mixing and cooling in the ice bath. The mixture was filtered, aqueous layer was separated and the organic layer was extracted with 1.5N acetic acid (5 mL). Combined aqueous layer was washed with isopropyl acetate (12 mL) and assayed by HPLC. Aqueous solution (176 mL) contains 58.4 mg/mL hydrocodone (90% yield), purity 96 area %.

Provenance & Evidence