To a stirred solution of 5-bromo-2-chloro-4-iodopyridine (20.0 g, 63.09 mmol, 1.0 eq.) in N,N-dimethylformamide (DMF, 200 mL) at room temperature and under argon protection was added sequentially methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (16.15 mL, 126.18 mmol, 2.0 eq.) and iodide cuprous iodide (CuI, 24.02 g, 126.18 mmol, 2.0 equiv). The reaction mixture was heated to 100 °C with continuous stirring for 6 hours. The reaction progress was monitored by thin layer chromatography (TLC) and non-polar spots were observed. After completion of the reaction, the mixture was diluted with water (200 mL), filtered and washed sequentially with n-pentane (1 L) and cold water (3 L). The organic layer was separated and dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure at 30 °C. The crude product was purified by silica gel column chromatography (100-200 mesh) with petroleum ether solution of 5% ethyl acetate as eluent to afford the target product 5-bromo-2-chloro-4-trifluoromethylpyridine (9.0 g, yield 55.2%) as a liquid compound.TLC conditions: petroleum ether solution of 5% ethyl acetate; Rf value: 0.7.
