Cesium carbonate → (+)-[N-(Benzyloxycarbonyl)morphinan-3-yloxy]methyl pivalate

Participants

Reaction Steps

To (+)-3-hydroxy-N-(benzyloxycarbonyl)morphinan (12.0 g, 31.8 mmol) from Example 1 and cesium carbonate (11.4 g, 35.0 mmol) in acetone (150 mL) was added iodomethyl pivalate (8.46 g, 35.0 mmol) (see Bristol-Myers Squibb Company, U.S. Pat. No. 5,470,845 A1 (1995/11/28), Appl.; US1994-266843 (1994 Jul. 5)) at room temperature. The reaction mixture was stirred vigorously at room temperature overnight. The acetone was then removed by rotary evaporation under vacuum. To the residue was added saturated NaHCO3 solution. The mixture was extracted with EtOAc (150 mL×2). The combined organics were washed with 1N HCl solution (100 mL), dried over MgSO4, filtered, and evaporated under vacuum to provide the crude product, which was further purified by prep reverse-phase HPLC to afford the title compound (13.2 g, 84%) as a yellow gum.

Provenance & Evidence