[Synthesis]
General method: 5-cyclopropylpyridin-2-amine (1 mmol) was dissolved in dibromo(chloro)methane (6 mL) with the corresponding Cu(II) halide (0.5 mmol) at 25 °C and under argon protection. Alkyl nitrite (1.1 mmol) was added slowly and dropwise over 5 min, followed by stirring of the reaction mixture at a suitable temperature (see Tables 1 and 2) until GC-MS analysis showed complete consumption of the feedstock. Upon completion of the reaction, the mixture was poured into 1N NaOH solution (20 mL), stirred for 1 h, and then extracted with dichloromethane (3 x 20 mL). The organic phases were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography using dichloromethane as eluent.
2-Bromo-5-cyclopropylpyridine (2a): 76% yield. Thin layer chromatography Rf value was 0.49 (unfolding agent: dichloromethane). NMR hydrogen spectrum (400MHz, CDCl3) δ 8.17 (d, J=2.4Hz, 1H), 7.34 (d, J=8.2Hz, 1H), 7.15 (dd, J=8.2,2.4Hz, 1H), 1.89-1.82 (m, 1H), 1.10-0.98 (m, 2H), 0.75-0.64 (m, 2H) . NMR carbon spectrum (100 MHz, CDCl3) δ 148.6,138.8,138.7,135.4,127.5,12.5,9.1. GC-MS analysis: retention time tR = 7.031 min, mass-to-charge ratio m/z (relative abundance) 197 (43.52%), 199 (41.85%). |