Tetrahydrofuran → (3-Fluoro-5-(trifluoromethyl)phenyl)(4-(trifluoromethyl)pyrimidin-2-yl)methanone

Participants

Reaction Steps

A mixture of 2-(methylsulfonyl)-4-(trifluoromethyl)pyrimidine (1.55 g, 6.63 mmol) and 2-(3-fluoro-5-(trifluoromethyl)phenyl)acetonitrile (1.53 g, 7.23 mmol) in anhydrous THF (45 mL) was stirred at room temperature under Argon. To the reaction mixture NaHMDS (8.8 mL, 1.0 M in THF, 8.8 mmol) was added during a 2-min period. The reaction mixture was stirred at room temperature for 1 h. 12 mL of the above reaction mixture was transferred to another round-bottomed flask. Saturated NH4Cl (10 mL) and THF (10 mL) were added, followed by the addition of Na2O2 (1.15 g, 14.7 mmol) at −30° C. The reaction mixture was stirred at room temperature for 5 h, followed by addition of MeOH. The solids were removed by filtration and the filtrate was concentrated. The residue was dissolved in EtOAc and the solution washed with H2O, saturated NaCl, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give pure (3-fluoro-5-(trifluoromethyl)phenyl)(4-(trifluoromethyl)pyrimidin-2-yl)methanone (0.45 g, 71.5% for two steps). NMR: 400 MHz 1H (CDCl3) 9.18 ppm, d, J=5.1 Hz, 1 H;, 8.08 ppm, s, 1 H;, 7.89 ppm, d, J=8.8 Hz, 1 H;, 7.81 ppm, d, J=5.1 Hz, 1 H;, 7.46 ppm, dt, J=7.8, 1.5 Hz, 1 H.

Provenance & Evidence