(Trifluoromethyl)trimethylsilane → 1-(5-bromo-2-fluorophenyl)-2,2,2-trifluoroethan-1-ol

Participants

Reaction Steps

A solution of 5-bromo-2-fluorobenzaldehyde (5.05 g, 24.9 mmol) in THF (200 mL) was cooled in a wet ice bath and treated dropwise with TMS-CF3 over five minutes. After stirring for 10 minutes, a solution of tetrabutylammonium fluoride (TBAF) in THF (1.0 mL, 1.0M) was added dropwise over 5 minutes. After stirring for 10 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was treated with 1N HCl (50 mL) and allowed to stir for 2 hours. The mixture was diluted with 1N HCl (50 mL) and extracted with EtOAc (200 mL). The organic layer was washed with saturated aqueous NaHCO3 (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography (silica gel, hexanes/EtOAc, 100:0 to 95:5) provided the title compound (3.28 g, 48%) as a colorless liquid. 1H NMR (500 MHz, CDCl3) δ 7.76 (dd, J=6.0, 2.0 Hz, 1H), 7.50 (ddd, J=8.5, 4.5, 2.5 Hz, 1H), 7.00 (overlapping dd, J=9.0, 9.0 Hz, 1H), 5.39 (overlapping dq, J=6.0, 6.0 Hz, 1H), 2.86 (d, J=5.5 Hz, 1H).

Provenance & Evidence