The general procedure for the synthesis of 2-chloro-3-fluoro-4-iodopyridine using 2-chloro-3-fluoropyridine as a starting material was as follows: a lithium 2-diisopropylammonium solution (2M, dissolved in a mixed solvent of tetrahydrofuran/ethylbenzene/heptane, 155 mL, 0.31 mol) was added slowly and dropwise over a period of 40 min at -70 °C to a 2-chloro-3-fluoropyridine (31 g, 0.235 mol) tetrahydrofuran (200 mL) solution. After the dropwise addition, the reaction mixture was continued to be stirred at -70 °C for 4 hours. Subsequently, a solution of iodine (69 g, 0.2 mol) in tetrahydrofuran (100 mL) was added dropwise over a period of 30 min, and after keeping the reaction at -70 °C for 30 min, the reaction was slowly warmed up to room temperature, and the warming up process was controlled to be completed in 1 hour. The reaction mixture was poured into aqueous sodium bisulfite solution (20% v/v, 2 L) and extracted with ether (3 x 300 mL). The organic phases were combined and washed sequentially with aqueous sodium metabisulfite (20% v/v, 2L) and water (200 mL), dried with anhydrous sodium sulfate and concentrated under reduced pressure to give a colorless oily substance. The oily material was ground with ether to afford the target product 2-chloro-3-fluoro-4-iodopyridine as a reddish brown solid (28 g, 46% yield). The product was confirmed by NMR hydrogen spectrum (400 MHz, CDCl3): δ 7.87 (d, J=5.0 Hz, 1H), 7.66 (ddd, J=5.0,4.0,0.4 Hz, 1H).
