The general procedure for the synthesis of 2,6-dichloro-3-(trifluoromethyl)pyridine from (trifluoromethyl)trimethylsilane and 2,6-dichloro-3-iodopyridine is as follows:
Step 1: Potassium fluoride (2.24 g, 38.5 mmol) and copper(I) iodide (7.33 g, 38.5 mmol) were weighed in a flask and the mixture was heated using a gas burner while gently shaking under high vacuum until the contents changed to light yellowish green color. After cooling to room temperature, anhydrous N,N-dimethylformamide (50 mL) and anhydrous tetrahydrofuran (10 mL) were added, followed by trimethyl(trifluoromethyl)silane (5.5 mL, 35 mmol). The mixture was heated to 50 °C and stirred for 21 hours. A mixed solution of 2,6-dichloro-3-iodopyridine (9.59 g, 35.0 mmol) in anhydrous N,N-dimethylformamide (10 mL) and anhydrous tetrahydrofuran (20 mL) was added dropwise at 50 °C to the above reaction mixture. After continuing to stir at 50 °C for 21 hours, trimethyl(trifluoromethyl)silane (0.55 mL, 3.5 mmol) was added and the mixture was stirred for 24 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, poured into 12% ammonia and the mixture was extracted with ether three times. The combined organic layers were washed sequentially with 12% ammonia, 1 M hydrochloric acid, saturated aqueous sodium bicarbonate and saturated brine, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane:hexane=1:4) to afford 2,6-dichloro-3-(trifluoromethyl)pyridine (7.32 g, 97.3% yield).
