Hydrogen Peroxide → Samidorphan

Participants

Reaction Steps

To an ice/water cooled suspension of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carbonitrile [P2] (6.0 g, 17.1 mmol) and potassium carbonate (7.09 g, 51.37 mmol) in DMSO (120 mL) was added hydrogen peroxide (25 mL, 35 wt. % in H2O) drop wise at a rate to ensure the temperature remained below 20° C. The mixture was stirred for 2 hours then diluted with DCM (800 mL). The solution was washed with water (3×500 mL) before the organic phase was dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave crude product that was purified by trituration with methanol giving (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carboxamide [P3] (4.50 g, 71% yield); LC/MS (r.t. 10.1 minutes [5 to 95% B]), 369 (M+H)+.

Provenance & Evidence