Acetonitrile (100 mL), elemental iodine (48.9 g, 192.8 mmol), cuprous iodide (23.9 g, 125.3 mmol), and tert-butyl nitrite (14.9 g, 144.6 mmol) were sequentially added to a 500 mL three-necked flask under nitrogen protection. Under cooling in an ice bath, 2-amino-3-bromo-5-chloropyridine (20.0 g, 96.4 mmol) was slowly added, followed by heating the reaction mixture to 60 °C and stirring the reaction for 2 hours. After completion of the reaction, water (45 mL) was added to the reaction mixture and the solid was collected by filtration. The filter cake was washed with ethyl acetate (45 mL x 1) and after combining the filtrates, the aqueous phase was further extracted with ethyl acetate (200 mL x 2). The organic phases were combined, washed with saturated aqueous sodium thiosulfate (110 mL × 2) and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure, and the residue was pulped with a small amount of methanol, filtered, and dried to give 21.9 g of 3-bromo-5-chloro-2-iodopyridine white solid in 71.2% yield.
