170886-13-2

131748-14-6

Example 1 Preparation of 4-chloro-2-trifluoromethylpyridine: In a 25 mL round-bottomed flask equipped with a reflux condenser, a magnetic stirrer, and vented with inert gas, 1.63 g (10.0 mmol) of 2-trifluoromethyl-4-hydroxypyridine was dissolved in a solvent mixture of 4.9 mL of cyclohexane and 0.077 mL of DMF. At room temperature, 2.19 mL (25.0 mmol) oxalyl chloride was slowly added. The reaction mixture was heated to reflux for 3 hours and subsequently cooled to room temperature. 18 mL of water was added slowly and dropwise (watch for gas release), then the reaction mixture was extracted with 18 mL of methyl tert-butyl ether (MTBE). The organic layer was separated, washed with 1 M sodium bicarbonate (NaHCO3) solution and dried over anhydrous sodium sulfate (Na2SO4). After filtration, the solvent was evaporated under reduced pressure to give the crude product. The crude product was dissolved in 12 mL of hexane and stirred at room temperature for 5 min, filtered and evaporated under reduced pressure to give 0.9 g of 4-chloro-2-trifluoromethylpyridine as a yellow liquid. The product was analyzed by GC-EI-MS, showing molecular ion peaks at m/z 181 (M+) and m/z 183 (M+2).