Ethyl 2,4-dichloronicotinate

26452-80-2

62022-04-2

To a solution of tetrahydrofuran (THF, 40 mL) containing diisopropylamine (2.4 mL, 16.9 mmol) was slowly added n-butyllithium (10.6 mL, 16.9 mmol, 1.6 M hexane solution) at -78 °C and protected by an inert atmosphere and the reaction was stirred for 15 min. Maintaining the temperature at -78 °C, 2,4-dichloropyridine (1.8 mL, 16.9 mmol) was added dropwise and the reaction mixture continued to be stirred at -78 °C for 2 hours. Subsequently, ethyl cyanoformate (4.0 mL, 40.4 mmol) was added and the reaction mixture continued to be stirred at -78 °C for 1 h before slowly warming up to room temperature. The reaction mixture was partitioned with water and ethyl acetate to separate the organic layer. The organic layer was washed sequentially with saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product was purified by fast column chromatography (solid phase extraction on silica gel, gradient elution with pentane:ether from 1:0 to 4:1) to afford ethyl 2,4-dichloronicotinate as a colorless oil (1.6 g, 43% yield). The structure of the product was confirmed by 1H NMR (CDCl3, 400 MHz): δ 8.34 (1H, d, J = 5.4 Hz), 7.33 (1H, d, J = 5.4 Hz), 4.49 (2H, q, J = 7.1 Hz), 1.43 (3H, t, J = 7.1 Hz).