[Synthesis]
General procedure for the synthesis of N-Boc-3-aminopyridine from di-tert-butyl dicarbonate: 3-aminopyridine (4.29 g, 45.6 mmol) was dissolved in tetrahydrofuran (THF, 100 mL). A solution of 1 M sodium hexamethyldisilazide (NaHMDS, 100 mL, 100 mmol) in THF was slowly added dropwise through the addition funnel. After 15 min of reaction, the THF (100 mL) solution of di-tert-butyl dicarbonate (Boc2O, 11.92 g, 54.6 mmol) was continued to be added dropwise. After another 15 min, the reaction was quenched with water (100 mL) and extracted with ethyl acetate (EtOAc, 500 mL). The organic layer was washed with water (2 x 100 mL). The aqueous layers were combined and extracted again with ethyl acetate (200 mL). All organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by fast column chromatography (30% ethyl acetate/dichloromethane) to afford the target product, N-tert-butoxycarbonyl-3-aminopyridine (5.195 g, 30.5 mmol, 67% yield), as an orange solid.1H NMR (400 MHz, DMSO-d6) δ: 9.53 (s, 1H), 8.57 (s, 1H), 8.14 (d J = 4.4 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.25 (m, 1H), 1.44 (s, 9H).ESI-MS, m/e: 195.3 (M + 1). Elemental analysis C10H14N2O2: Calculated values: C, 61.84; H, 7.27; N, 14.42; Measured values: C, 61.94; H, 7.18; N, 14.38. |