The general procedure for the synthesis of 2-chloro-5-fluoro-4-iodopyridine using 2-chloro-5-fluoropyridine as starting material was as follows: 2-chloro-5-fluoropyridine (10.0 g, 76.0 mmol, 1.0 eq.) was dissolved in anhydrous tetrahydrofuran (THF, 100 mL) under nitrogen protection and cooled to -78 °C. Lithium diisopropylammonium (LDA, 58 mL, 116 mmol, 2 M in THF) was added slowly and the reaction mixture was kept stirred at -78 °C for 3 hours. Subsequently, a solution of iodine (I2, 23.2 g, 91.0 mmol) in THF (100 mL) was slowly added at the same temperature. The reaction mixture continued to be stirred at -78 °C for 1 h. The reaction was then quenched with water (200 mL). The reaction mixture was slowly warmed to room temperature and extracted with ethyl acetate (EtOAc, 100 mL x 2). The organic layers were combined, washed with brine (50 mL × 2), dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent being petroleum ether (PE) to ethyl acetate/petroleum ether (1/20, v/v) to afford 2-chloro-5-fluoro-4-iodopyridine (11.8 g, 60% yield) as a white solid.1H NMR (400 MHz, CDCl3): δ 8.13 (s, 1H), 7.76 (d, 1H).
