Phosphate → (4S)-3-[(2S)-2-(biphenyl-4-ylmethoxy)propanoyl]-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A butyllithium solution (9.7 M in hexanes, 7.64 mL, 74 mmol) was added drop-wise to a solution of C3 (13.5 g, 70.6 mmol) in tetrahydrofuran (800 mL) at −78° C., and the mixture was stirred for 30 minutes at −78° C. A solution of C6 (21.3 g, 78 mmol) in tetrahydrofuran (50 mL) was then added slowly, and the reaction was stirred at −78° C. for 30 minutes and then at 25° C. for about 3 hours. The reaction mixture was then poured into phosphate buffer (pH 7) and extracted with ethyl acetate (2×). The organic extract was washed with aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated to a minimal volume. The resultant residue was then precipitated by addition of 1 liter of hexanes. The solid white product was collected by filtration, and the filtrate was concentrated. The resultant residue was purified by silica gel chromatography (gradient: 9:1 hexanes:ethyl acetate to 6:4 hexanes:ethyl acetate), to provide C7 as a white solid. Yield: 22.8 g, 75 LCMS m/z 430.3 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 0.85 (3H, s), 1.35 (3H, d, J=6.6 Hz), 1.57 (3H, s), 4.36 (2H, apparent s, actual AB quartet, J=12.3 Hz), 5.21 (1H, s), 5.21 (1H, q, J=6.6 Hz), 7.23 (2H, m), 7.36 (8H, m), 7.61 (4H, m).

Provenance & Evidence