General procedure for the synthesis of 4-chloro-6-trifluoromethylpyrimidine from 6-trifluoromethyl-4-hydroxypyrimidine: 6-(trifluoromethyl)pyrimidin-4-ol (5.0 g, 30.5 mmol), phosphorochloridic acid chloride (3.41 mL, 36.6 mmol), and quinoline (2.16 mL, 18.3 mmol) were dissolved in toluene (50 mL), and the reaction was stirred at 100°C for 5 hours. After completion of the reaction, the reaction mixture was diluted with water and extracted three times with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by fast column chromatography (eluent: 10% ethyl acetate/hexane) to afford the target product 4-chloro-6-trifluoromethylpyrimidine (1.20 g, 21.6% yield).1H NMR (400 MHz, CDCl3) δ: 9.21 ppm (1H, s), 7.78 ppm (1H, s).
