Hydrogen Peroxide → (2r)-(4-Chlorophenyl)[3-(Trifluoromethyl)phenoxy]ethanoic Acid

Participants

Reaction Steps

To a solution of 3-(Trifluoromethyl)phenol 5 (10.82 g, 66.85 mmol) in THF (30 mL) was added lithium-tert-butoxide (5.34 g, 66.85 mmol) at 0° C. and stirred at RT for 30 min. The resulting lithium phenoxide solution was added drop wise to a solution of (2S)-1-oxo-1-(pyrrolidin-1-yl)propan-2-yl 2-bromo-2-(4-chlorophenyl)acetate 4 (25.0 g, 66.85 mmol) in THF (160 ml) at −5° C. The reaction mixture was stirred for 4 h at −5° C. To the solution was added a pre-mixed solution of H2O2 (30% solution, 151 g, 1336.989 mmol) and LiOH,H2O (6.8 g, 167.11 mmol) in water (150 mL) at 0-5° C. over 30 min. The reaction mixture was stirred 0-5° C. for 1 h and quenched with saturated aqueous sodium bisulfite (200 ml). The reaction mixture was made acidic (pH ˜2) with 1(N) HCl at cooling condition. The organic layer was separated and concentrated under reduced pressure. The crude residue was dissolved in ethyl acetate (150 mL) and washed with water (2×80 mL) followed by brine solution (80 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash chromatography on 100-200 mesh silica-gel (12-15% ethyl acetate-hexane) to afford (2R)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetic acid 7 (11.2 g, 51%) as off white solid.

Provenance & Evidence