2-Chloro-4-iodonicotinonitrile

6602-54-6

1171919-75-7

Step 1: Synthesis of 2-chloro-4-iodo-3-cyanopyridine Under argon protection, n-butyllithium (2.4 M hexane solution, 3.0 mL, 7.2 mmol) was slowly added dropwise to an anhydrous tetrahydrofuran (20 mL) solution of diisopropylamine (0.728 g, 7.2 mmol), and the reaction mixture was stirred for 30 min at -30 °C, and subsequently cooled to -78 °C. At this temperature, a solution of 2-chloro-3-cyanopyridine (1.0 g, 7.2 mmol) in anhydrous tetrahydrofuran (10 mL) was slowly added and stirring was continued at -78 °C for 60 min. Subsequently, anhydrous tetrahydrofuran (10 mL) solution of iodine (1.8 g, 7.2 mmol) was added dropwise and the reaction mixture was stirred at the same temperature for 30 minutes. Upon completion of the reaction, the reaction was quenched with saturated ammonium chloride solution (50 mL), diluted with water (50 mL) and extracted with ethyl acetate (100 mL x 3). The organic phases were combined, washed with brine (100 mL x 3), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (petroleum ether: ethyl acetate = 80:1) to afford the yellow solid product 2-chloro-4-iodo-3-cyanopyridine (0.357 g, 19% yield). 1H NMR (400MHz, DMSO-d6) δ 8.32 (d, J=5.2Hz, 1H), 8.15 (d, J=5.2Hz, 1H). MS (ESI+): m/z 264.9 [M+H]+.