Benzophenone → Hydromorphone

Participants

Reaction Steps

Dried morphine (0.324 g), benzophenone (1.47 g), chlorotris(triphenylphosphine)rhodium (I) (Wilkinson's catalyst) (0.055 g), and tert-butanol (6 mL) were charged into a glass hydrogenation bottle. The bottle was evacuated and filled with hydrogen. The mixture was magnetically agitated at ambient temperature (24–29° C.) at 16 psi for 16 hours. Potassium tert-butylate (0.804 g) was charged into the bottle with the reaction mixture in one portion, the mixture was magnetically agitated until all solids dissolved, then heated under nitrogen at 60° C. for 4.5 hours. After aging for additional 66 hours at ambient temperature the mixture was quenched with 1.5N acetic acid (6 mL) with mixing and cooling in the water bath, diluted with methanol to 250 mL in volumetric flask and assayed by HPLC. Solution contains 1.12 mg/mL hydromorphone (86% yield), purity 94 area %.

Provenance & Evidence