Hydrochloric Acid → HCID 56846972, compound

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (324 mg, 8.1 mmol, 60% dispersion in mineral oil) was washed under an argon atmosphere with hexane. DMSO (5 mL) was added and the mixture heated at 60° C. for 1 hour. Methyltriphenylphosphonium bromide (2.89 g, 8.1 mmol) was added and stirred at the same temperature for 1 hour. A solution of 17-(cyclopropylmethyl)-4,14-dihydroxy-6-oxomorphinan-3-carboxamide [P4] (0.6 g, 1.62 mmol) in DMSO (10 mL) was added and the mixture heated at 65° C. for 42 hours (A further 5 equivalents of Wittig reagent was added after 18 hours). The reaction was allowed to return to room temperature and partitioned between ethyl acetate (300 mL) and water (300 mL). The organic phase was washed with brine and dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave a residue that was stirred with hydrochloric acid (5%) for 30 minutes before washing with ethyl acetate. The aqueous phase was adjusted to pH8 by the addition of 2N sodium hydroxide solution and then extracted with DCM and dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave a residue that was purified by prep-HPLC [Xbridge Prep C18 OBD, 30×150 mm, 5 μm; Mobile Phase A: 10 mM NH4HCO3 (pH10), Phase B: MeCN; Flow: 50 ml/min; Column Temperature: 30° C.; Runtime: 25 min.] giving 17-(cyclopropylmethyl)-4,14-dihydroxy-6-methylenemorphinan-3-carboxamide [11] (180 mg, 30% yield); LC/MS (r.t. 13.3 minutes [5 to 95% B]), 369 (M+H)+.

Provenance & Evidence