Potassium Carbonate → 4-Bromo-1-chloro-2-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]benzene

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[(5-bromo-2-chloro-phenyl)methyl]phenol 17b (23.4 g, 78.7 mmol) in N,N-dimethylformamide (30 mL) was added potassium carbonate (54.0 g, 394.0 mmol) at room temperature. The mixture was warmed up to 90° C. and stirred for 30 min, and then 2,2,2-trifluoroethyl-p-toluensulfonate (20 g, 78.7 mmol) was added. The reaction mixture was warmed up to 140° C. and stirred for 12 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was partitioned between ethylacetate (200 mL) and water (200 mL). The aqueous layer was extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE to give the title compound 17c as a white solid (26.0 g, 87.2%, HPLC: 97.45%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.54 (d, 1H), 7.45 (m, 1H), 7.40 (d, 1H), 7.18 (d, 2H), 7.00 (d, 2H), 4.80-4.64 (m, 2H), 4.01 (s, 2H).

Provenance & Evidence