Oxalyl chloride → (4S)-4-benzyl-3-(5,5,5-trifluoropentanoyl)-1,3-oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 5,5,5-trifluoropentanoic acid (14.76 g, 95 mmol) and DMF (0.146 mL) in DCM (50 mL) was slowly added oxalyl chloride (8.27 mL, 95 mmol). After 2 h, the mixture was concentrated to dryness. A separate flask was changed with (S)-4-benzyloxazolidin-2-one (16.75 g, 95 mmol) in THF (100 mL) and then cooled to −78° C. To the solution was slowly added n-BuLi (2.5M, 37.8 mL, 95 mmol) over 10 min, stirred for 10 min, and then a solution of the above acid chloride in THF (50 mL) was slowly added over 5 min. The mixture was stirred for 30 min, and then warmed to room temperature. The mixture was quenched with saturated aqueous NH4Cl, then 10% aq LiCl was then added, and the mixture was extracted with Et2O. The organic layer was washed with saturated aqueous NaHCO3, then with brine, then dried with MgSO4, filtered and concentrated to dryness. The residue was purified by SiO2 chromatography (ISCO, 330 g column, eluting with a gradient from 100% hexane to 100% EtOAc) to afford the product Preparation 1B; (25.25 g, 85%): 1H NMR (400 MHz, CDCl3) δ ppm 7.32-7.39 (2H, m), 7.30 (1H, d, J=7.05 Hz), 7.18-7.25 (2H, m), 4.64-4.74 (1H, m), 4.17-4.27 (2H, m), 3.31 (1H, dd, J=13.35, 3.27 Hz), 3.00-3.11 (2H, m), 2.79 (1H, dd, J=13.35, 9.57 Hz), 2.16-2.28 (2H, m), 1.93-2.04 (2H, m).

Provenance & Evidence