General procedure for the synthesis of 2-fluoro-3-iodo-5-methylpyridine from 2-fluoro-5-methylpyridine: 2.5 M hexane solution of n-butyllithium (719 mL, 1.80 mmol) was added dropwise to an anhydrous tetrahydrofuran (5 mL) solution of diisopropylamine (252 mL, 1.80 mmol) under argon gas protection, keeping the reaction temperature at 20 °C and stirring for 30 min. Subsequently, the reaction system was cooled to -78 °C and anhydrous tetrahydrofuran (1 mL) solution of 2-fluoro-5-methylpyridine (200 mg, 1.80 mmol) was slowly added over 10 min. The reaction was continued to stir at -78 °C for 3.5 h. Anhydrous tetrahydrofuran (1 mL) solution of iodine (457 mg, 1.80 mmol) was then added. The mixture was stirred at -78 °C for another 1 h before the reaction was quenched with 2 mL of water and 10 mL of tetrahydrofuran. The mixture was warmed to 0 °C and diluted with 50 mL of water, followed by the addition of sodium bisulfite until the solution became colorless. After extraction with dichloromethane (3 x 30 mL), the organic layers were combined and dried with magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: dichloromethane/cyclohexane, 5/5, v/v) to afford 2-fluoro-3-iodo-5-methylpyridine (275 mg, 1.16 mmol) as a colorless solid in 65% yield. The product characterization data were as follows: rf (SiO2, dichloromethane/cyclohexane, 5/5, v/v) 0.21; melting point 40-45 °C; IR (KBr) ν 1049, 1379, 1446, 2930 cm-1; 1H NMR (200 MHz, CDCl3) δ 2.28 (s, 3H, CH3), 7.95 (m, 2H, H-4, H -6); 13C NMR (50 MHz, CDCl3) δ 17.0 (CH3), 75.4 (d, 2JC-F = 44 Hz, C-3), 132.7 (d, 4JC-F = 5 Hz, C-5), 146.8 (d, 3JC-F = 13 Hz, C-6), 150.4 (C-4), 160.4 (d, 1JC-F = 232 Hz, C-2); 19F NMR (470 MHz, CDCl3) δ 61.7; ESI-MS m/z 237.89 [M + H]+.
