Pyridine, 5-(chloromethyl)-2-(trifluoromethyl)- (9CI)

386704-04-7

386715-33-9

General procedure for the synthesis of 5-chloromethyl-2-trifluoromethylpyridine from 6-trifluoromethyl-3-pyridine methanol: At room temperature and under nitrogen protection, [6-(trifluoromethyl)pyridin-3-yl]methanol (4.41 g, 24.9 mmol) was dissolved in anhydrous dichloromethane (82.5 ml) and triethylamine (4.2 ml, 30.1 mmol) and 4-dimethylamino pyridine (21.5 mg, 0.176 mmol). The reaction mixture was cooled to 0 °C, methanesulfonyl chloride (3.0 ml, 38.8 mmol) was added slowly dropwise and stirred at 0 °C for 1 h. The mixture was gradually warmed up to room temperature and continued to be stirred for 22 h. After the reaction was completed, the reaction was carried out at room temperature. After completion of the reaction, the mixture was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography with the eluent ratio of hexane:ethyl acetate=9:1→1:1 to afford 5-(chloromethyl)-2-trifluoromethylpyridine. The yield was 3.99 g, 84%, as yellow liquid.