1-Bromo-4-(trifluoromethoxy)benzene → 1-(3-Bromo-4-fluorophenyl)-1-(tetrahydropyrimidin-2-yl)-1-[4-(trifluoromethoxy)phenyl]methanol

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Reaction Conditions

Reaction Steps

A mixture of magnesium (2.13 g, 87.7 mmol) in THF at 50° C. is treated dropwise with a solution of 1-bromo-4-(trifluoromethoxy)benzene (21.1 g, 87.7 mmol) in THF over a period of 20 min., stirred at 50° C. for an additional 1.5 h, cooled to room temperature, treated with copper(I) iodide (0.13 g, 0.70 mmol) and a solution of 2-(3-bromo-4-fluorobenzoyl)-2,3,4,5-tetrahydropyrimidine (10.0 g, 14.9 mmol) in THF, heated at 65° C. overnight, cooled to room temperature and diluted with ethyl acetate and saturated aqueous ammonium chloride. The phases are separated. The organic phase is washed sequentially with water and brine, dried over sodium sulfate, and concentrated to afford 18.5 g of a brown oil. The oil is purified by flash chromatography (silica, 90:10:0.5 methylene chloride/methanol/concentrated ammonium hydroxide as eluent) to afford the title compound as a yellow oil, 10.0 g (64% yield), identified by NMR and mass spectral analyses. 1H NMR (300 MHz, CDCl3) δ 7.60 (dd, J=6.4, 2.3 Hz, 1H), 7.41 (dd, J=6.9, 2.0 Hz, 2H), 7.28-7.20 (m, 3H), 7.10 (t, J=8.3 Hz, 1H), 3.50 (m, 6H), 1.96 (m, 2H); ESI MS m/z 447 [C18H15BrF4N2O2+H]+.

Provenance & Evidence