To a solution of 2-amino-5-methylpyridine (13) (20.0 g, 185 mmol) in fluoboric acid (50 wt% aqueous solution, 50 mL) was added sodium nitrite (16.6 g, 240 mmol) in batches at -10 °C while controlling the temperature of the reaction to be below 0 °C. After addition, the reaction mixture was stirred at 0 °C for 30 min, then warmed to 50 °C and continued stirring for 30 min. After completion of the reaction, the reaction was cooled to room temperature and the pH was adjusted to 9-10 with saturated aqueous sodium carbonate solution (250 mL), followed by extraction with dichloromethane (4 x 125 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by alumina column chromatography (eluent: dichloromethane) to afford 2-fluoro-5-methylpyridine (14) (7.50 g, 69 mmol) as a yellow oil in 37% yield. Thin-layer chromatography (TLC) analysis: Rf (Al2O3, dichloromethane) 0.92. Infrared spectra (IR, NaCl plate) νmax: 1246, 1379, 1486, 2929 cm-1. nuclear magnetic resonance hydrogen spectra (1H NMR, 200 MHz, CDCl3) δ: 2.25 (s, 3H, CH3), 6.75 (dd, 1H, J = 8.2 Hz, 3JH-F = 3.0 Hz, H-3), 7.52 (m, 1H, H-4), 7.94 (s, 1H, H-6). Nuclear magnetic resonance carbon spectrum (13C NMR, 50 MHz, CDCl3) δ: 17.4 (CH3), 108.8 (d, 2JC-F = 38Hz, C-3), 130.6 (C-5), 141.7 (d, 3JC-F = 8Hz, C-4), 147.2 (d, 3JC-F = 14Hz, C-6), 162.1 (d. 1JC-F = 236Hz, C-2).
