Pivaloyl chloride → (R)-4-benzyl-3-(2-(4-chloro-3-fluorophenyl)acetyl)oxazolidin-2-one

Participants

Reaction Steps

Trimethylacetyl chloride (1.68 g, 13.9 mmol) was added to a solution of 2-(4-chloro-3-fluorophenyl)acetic acid (2.50 g, 13.3 mmol) and TEA (d. 0.726; 2.00 mL, 14.3 mmol) in dry THF (100 mL) at 0° C. and stirred at room temperature. In a separate flask, n-BuLi (6.424 mL, 14.58 mmol) was added to (R)-4-benzyloxazolidin-2-one (2.47 g, 13.9 mmol) in dry THF (100 mL) at −78° C. The reaction was strirred for 20 minutes at −78° C., and then the (R)-4-benzyloxazolidin-2-one solution was added dropwise to the 0° C. mixed anhydride solution. The reaction was allowed to stir overnight at room temperature. The reaction was quenched with water (100 mL) and diluted with ethyl acetate (100 mL). The layers were separated, and the organics were washed with brine, dried (MgSO4) and concentrated to a residue. The resulting residue was purified by flash chromatography to give (R)-4-benzyl-3-(2-(4-chloro-3-fluorophenyl)acetyl)oxazolidin-2-one (2.79 g, 8.02 mmol, 60.5% yield). 1H NMR (400 MHz, CDCl3) 7.37 (t, J=8.2 Hz, 1H), 7.33-7.26 (m, 3H), 7.18-7.12 (m, 3H), 7.07 (d, J=8.2 Hz, 1H), 4.73-4.65 (m, 1H), 4.33-4.18 (m, 4H), 3.27 (dd, J1=3.5 Hz, J2=13.3 Hz, 1H), 2.77 (dd, J1=9.4 Hz, J2=13.7 Hz, 1H).

Provenance & Evidence