N-Methylmorphine → (4S)-3-[3-(5-methylindolyl)propanoyl]-4-phenyl-1,3-oxazolidin-2-one

Participants

Reaction Steps

To the suspension of (4S)-4-phenyl-1,3-oxazolidin-2-one (6.85 g, 42 mmol) in anhydrous THF (130 mL) was added BuLi (26.3 mL, 42 mmol) at −78° C. and the mixture was stirred under argon (0.5 h). To the above suspension was added a solution of active ester prepared by reacting 3-(5-methylindolyl)propanoic acid 7 (10.23 g, 50.39 mmol) in anhydrous THF (130 mL) and trimethylacetyl chloride (5.10 g, 50.39 mmol) in the presence of N-methyl morphine (6.06 g, 50.39 mmol) at 0° C. under argon, followed by stirring at −78° C. (1 h). The combined reaction mixture was stirred at −78° C. for an additional 2 h, then the solution was warmed to room temperature and stirred overnight. The reaction was quenched by the addition of ice-cold saturated NH4Cl solution (120 mL), extracted with EtOAc, washed with brine and dried (Na2SO4). Evaporation provided a residue, which was purified by silica gel flash chromatography to provide 8 as colorless oil. (12.7 g, 87% yield). 1H NMR (d6-DMSO) δ 7.36-7.23 (m, 8H), 6.94 (dd, 1H, J=1.5 Hz & 8.5 Hz), 6.28 (dd, 1H, J=0.8 Hz & 3.1 Hz), 5.43: (dd, 1H, J=3.5 Hz & 8.6 Hz), 4.70 (t, 1H, J=8.8), 4.40 (s, 1H), 4.40-4.37 (m, 2H), 4.15 (dd, 1H, J=3.5 Hz & 8.8 Hz), 3.41-3.30 (m, 2H), 2.36 (s, 3H). FABMS (+Ve) m/z 348 [M+], 349 [MH+]. Anal. Calcd for C21H20N2O3 C, 72.40; H, 5.79; N, 8.04. Found C, 72.33; H, 5.77; N, 8.15.

Provenance & Evidence