Acetic Acid → 6-cyclopropyl-2-(2-trifluoromethyl-phenyl)-3H-pyrimidin-4-one

Participants

Reaction Steps

To a solution of (1-cyclopropyl-vinyl)-dimethylamine in tetrahydrofuran (400 mL) at 0° C. under nitrogen was added a solution of 2-trifluoromethylbenzoyl isocyanate in tetrahydrofuran (50 mL), in a dropwise fashion. The reaction was stirred for 0.5 hour, then ammonium acetate (78 g, 1000 mmol) and acetic acid (400 mL) was added. The reaction mixture was heated at reflux for 3 hours with continuous removal of tetrahydrofuran, then cooled and poured into water (1.2 L). The resulting precipitate was collected by filtration, washing with water and ether to provide 6-cyclopropyl-2-(2-trifluoromethyl-phenyl)-3H-pyrimidin-4-one (28.79 g, 56% yield) as a white solid which is a mixture of the title compound and (2-trifluoromethyl-benzoyl)-urea (91:9 by HPLC). 1H-NMR (500 MHz, DMSO-d6) δ 12.7 (br s, 1H), 7.87 (d, J=7.6 Hz, 1H), 7.79 (m, 2H), 7.73 (d, J=7.5 Hz, 1H), 6.32 (s, 1H), 1.93 (m, 1H), 0.90 (m, 4H), [urea: 10.8 (br s, 1H), 7.45 (br s, 1H)] ppm; LC-MS 280.96 (M+H); Rt (Method A) 2.961 minutes (title compound), 2.313 minutes (urea impurity).

Provenance & Evidence