General procedure for the synthesis of 2-chloro-3-bromo-6-methoxypyridine from 2-chloro-6-methoxypyridine: To a stirred solution of 2-chloro-6-methoxypyridine (7.00 g, 48.8 mmol) in acetonitrile (25 mL) was added N-bromosuccinimide (NBS, 13.0 g, 73.1 mmol) at room temperature. The reaction mixture was refluxed for 24 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium thiosulfate (Na2S2O3) and extracted with ethyl acetate (EtOAc). The organic layer was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, hexane-ethyl acetate = 98:2) afforded 2-chloro-3-bromo-6-methoxypyridine (6.83 g, 63% yield) as a colorless solid. The product was characterized by the following data: melting point 64-65 °C; IR spectra (film, cm-1 ): 1584, 1551, 1466, 1408, 1344, 1306, 1256, 1155, 1121, 1022, 1009; 1H-NMR (CDCl3, 500 MHz) δ: 7.72 (d, J = 8.50 Hz, 1H), and 6.58 (d, J = 8.50 Hz, 1H), 3.92 (s, 3H); 13C-NMR (CDCl3, 125 MHz) δ: 162.4, 147.3, 143.8, 110.9, 110.1, 54.3; High-resolution mass spectrometry (ESI-TOF): the calculated value C6H6BrClNO [(M + H)+ ] was 221.9316, and the measured value was 221.9314.
