Phosgene → 6-Chloro-4-hydroxy-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydro-quinazolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of triethylamine (1.3 ml, 9.4 mmol) and 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone (2.1 g, 9.4 mmol) in diethyl ether (18 ml) was cooled to 0° C. under nitrogen atmosphere. In a separate round bottom, triphosgene (929 mg, 3.1 mmol) in diethyl ether (11 ml) was cooled to 0° C. To the phosgene mixture at 0° C. was added dropwise the trifluoroethanone mixture. After stirring for 15 minutes, to this reaction was added a mixture of triethylamine (1.3 ml, 9.4 mmol) and trifluoroethylamine in diethyl ether (18 ml). The reaction stirred for two hours at room temperature and then quenched with water (50 ml) and washed with saturated aqueous sodium bicarbonate solution (2×30 ml). The aqueous layer was extracted with ethyl acetate (3×100 ml) and the combined organic extracts were dried over Na2SO4, filtered and concentrated to give crude material which was purified by flash chromatography on silica gel (0-30% ethyl acetate/hexanes). This afforded 6-chloro-4-hydroxy-3-(2,2,2-trifluoroethyl)-4-(trifluoromethyl)-3,4-dihydroquinazolin-2(1H)-one as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 9.22 (s, 1H), 7.58 (s, 1H), 7.39 (dd, J=2.0 and 8.6 Hz, 1H), 6.84 (d, J=8.4 Hz), 4.71 (m, 1H), 4.38 (s, 1H), 4.18 (m, 1H). Exact Mass (Electrospray, M+H): Calc'd, 349.0173; Found, 349.0166.

Provenance & Evidence