2-Chloro-4-(difluoromethyl)pyridine

101066-61-9

1204296-03-6

Example 7: Preparation of 2-chloro-4-(difluoromethyl)pyridine Under stirring conditions, 2-chloropyridine-4-carboxaldehyde (990 mg, 7.0 mmol) was dissolved in dichloromethane (40 mL) and the solution was cooled to 0-5 °C. Diethylamino sulfur trifluoride (2.82 g, 2.31 mL, 17.5 mmol) was added slowly and dropwise over 15 min while the reaction temperature was controlled below 5 °C. The reaction solution was continued to be stirred under cooling conditions for 2 h, followed by slow warming to room temperature and left to stand overnight. The reaction mixture was slowly poured into a mixture of saturated sodium bicarbonate solution (30 mL) and ice (100 mL), ensuring that the pH of the mixture was always greater than 7. After 30 min, the reaction mixture was diluted with dichloromethane (30 mL) and water (20 mL) to separate the organic phase. The aqueous phase was further extracted with dichloromethane (2 x 20 mL). All organic extracts were combined, washed with water, dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated to give a yellow liquid. Purification by column chromatography afforded 2-chloro-4-(difluoromethyl)pyridine as a colorless liquid (813 mg, 71% yield). 1H NMR (CDCl3): δ 8.54 (d, 1H); 7.81 (dd, 1H); 7.45 (d, 1H); 6.71 (t, 1H).