General procedure for the synthesis of 2-bromo-5-fluoro-4-iodopyridine from 2-bromo-5-fluoropyridine: 2-bromo-5-fluoropyridine (10 g, 56.8 mmol) was dissolved in dry tetrahydrofuran (120 mL) under argon protection, cooled to -78 °C and stirred. A tetrahydrofuran solution of 2 M lithium diisopropylammonium (LDA) (34.1 mL, 68.2 mmol) was slowly added, keeping the temperature at -78 °C. The reaction mixture was stirred at this temperature for 40 min. Subsequently, a tetrahydrofuran (50 mL) solution of iodine (I2, 14.42 g, 56.8 mmol) was added dropwise and stirring was continued at -78 °C for 30 min. Upon completion of the reaction, the reaction was quenched with deionized water (500 mL) and slowly warmed to room temperature. The reaction mixture was extracted with ethyl acetate (2 x 500 mL) and the organic layers were combined. The organic layer was washed with saturated sodium thiosulfate solution (500 mL) to remove unreacted iodine, then dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using a petroleum ether solution of 3% ethyl acetate as eluent to afford 2-bromo-5-fluoro-4-iodopyridine (12 g, 39.8 mmol, 70% yield). The product was analyzed by LC/MS (ESI), m/e 301.0 [(M + H)+, C5H2BrFIN calculated value, 301.9]; LC/MS retention time (Method E): tR = 0.93 min; 1H NMR (400 MHz, chloroform-d) δ 8.13 (s, 1H), 7.91 (d, J = 4.4 Hz, 1H).
