Morphine → Hydromorphone

Participants

Reaction Conditions

Reaction Steps

A 1 L round bottom flask equipped with return condenser and nitrogen inlet was charged with methanol (650 mL) and morphine free base (50.0 g, 175.2 mmol). The mixture was stirred magnetically and heated to reflux under nitrogen until all morphine dissolves (45 min) then treated with the solution of the catalyst added via a cannula. The resulting brown solution was stirred and heated to reflux under nitrogen for 1 hour, then volume of the mixture was reduced to ca 400 mL by distillation. The resulting slurry was cooled to 7° C. in an ice bath, stirred at this temperature for 1 hour and filtered. The filtered solid was washed with isopropanol (3×60 mL) and dried in an oven at 95° C. to give hydromorphone free base as a white solid. The yield was 41.71 g, 83.4%.

Provenance & Evidence