Ammonia → 2,6-Dichloro-3-(trifluoromethyl)pyridine

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Reaction Steps

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 with a gas burner while gently shaking under high vacuum until the content becomes a pale-yellow green. After cooling to room temperature, anhydrous N,N-dimethylformamide (50 ml), anhydrous tetrahydrofuran (10 ml) and trimethyl(trifluoromethyl)silane (5.5 ml, 35 mmol) were added. The mixture was heated to 50° C., and stirred for 21 hrs. A mixed solution of 2,6-dichloro-3-iodopyridine (9.59 g, 35.0 mmol) in anhydrous N,N-dimethylformamide (10 ml)—anhydrous tetrahydrofuran (20 ml) was added dropwise to the above-mentioned reaction mixture at 50° C. After stirring at 50° C. for 21 hrs, trimethyl(trifluoromethyl)silane (0.55 ml, 3.5 mmol) was added, and the mixture was stirred for 24 hrs. The reaction mixture was cooled to room temperature, poured into 12% aqueous ammonia, and the mixture was extracted 3 times with diethyl ether. The combined organic layer was washed successively with 12% aqueous ammonia, 1M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:hexane=1:4) to give 2,6-dichloro-3-(trifluoromethyl)pyridine (7.32 g, yield 97.3%).

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