5-Bromo-2-chloro-3-cyanopyridine

405224-22-8

405224-23-9

Synthesis of 5-bromo-2-chloronicotinonitrile (13): 5-bromo-2-oxo-1,2-dihydropyridine-3-carbonitrile (12) (69 mg, 0.35 mmol) was mixed with phosphorus pentachloride (PCl5) (109 mg, 0.52 mmol) in phosphorus oxychloride (POCl3) (5 mL), and the reaction was carried out at reflux overnight. Upon completion of the reaction, the reaction mixture was cooled to room temperature and slowly added dropwise to ice water. The pH was adjusted to 8 with 4 M sodium hydroxide (NaOH) solution and then extracted with dichloromethane (CH2Cl2) (3 x 30 mL). The organic phases were combined, washed sequentially with aqueous sodium bicarbonate (NaHCO3) and saturated saline, dried over anhydrous sodium sulfate (Na2SO4), and concentrated under reduced pressure. Purification by column chromatography (petroleum ether/ethyl acetate=20:1) afforded the target product 5-bromo-2-chloronicotinonitrile (13) (63 mg, 84% yield) as a yellow solid. Melting point: 138~139°C. 1H NMR (400MHz, CDCl3): δ8.66 (d, J=2.4Hz, 1H), 8.12 (d, J=2.4Hz, 1H).