6-chloro-2-methoxynicotinaldehyde

17228-64-7

68-12-2

95652-81-6

GENERAL STEPS: 2-Chloro-6-methoxypyridine (5 g, 34.82 mmol) was dissolved in tetrahydrofuran (THF, 100 mL) under dry argon atmosphere and cooled to -78 °C. Tert-butyl lithium (tBuLi, 1.7 M, 18.5 mL, 31.34 mmol) was slowly added dropwise, keeping the temperature at -78 °C, and the reaction was stirred for 1 hour. Subsequently, N,N-dimethylformamide (DMF, 92.2 g, 31.34 mmol) was slowly added at the same temperature and stirring was continued for 2 hours. After completion of the reaction, the reaction was quenched with acetic acid and the mixture was poured into ice-cold water. The aqueous phase was alkalized with saturated sodium bicarbonate (NaHCO3) solution and subsequently extracted with ethyl acetate (EtOAc, 2 x 500 mL). The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography with the eluent being a mixed solvent of petroleum ether and ethyl acetate (10:1, v/v) to afford 6-chloro-2-methoxypyridine-3-carboxaldehyde as a white solid (3.8 g, 65% yield). The mass spectrum (ES+) showed m/z 172 [M+H]+; elemental analysis (C7H6ClNO2) was consistent with the theoretical value; 1H NMR (300 MHz, CDCl3) δ 10.17 (s, 1H), 8.07 (d, J=8.04Hz, 1H), 7.03 (d, J=8.04Hz, 1H), 3.79 (s, 3H).