2-Bromo-5-methoxypyridine

10167-97-2

105170-27-2

General procedure for the synthesis of 2-bromo-5-methoxypyridine from 2-amino-5-methoxypyridine: (a) 2-Amino-5-methoxypyridine (14.8 g, prepared according to the method described by JG Lombardino, J. Med. Chem., 1981, 24, 39) was dissolved in 60% hydrobromic acid (150 ml) and cooled to -10°C. Bromine (47.47 g) was added slowly and dropwise with stirring. A solution of sodium nitrite (20.53 g) in water (40 ml) was added dropwise to the resulting yellow suspension, keeping the reaction temperature below -5°C. The mixture was stirred to room temperature and cooled to 0°C after 0.5 h. A solution of sodium hydroxide (120 g) in water (100 ml) was added slowly. The mixture was fully extracted with ether, the ether extracts were combined and dried with anhydrous sodium sulfate, followed by evaporation of the solvent. The residue was purified by column chromatography on silica gel (150 g), using dichloromethane as eluent to give a yellow oil (14.1 g, 63% yield). This product was combined with a smaller batch (3.4 g) and purified by distillation under reduced pressure to give finally 2-bromo-5-methoxypyridine (16.4 g) with a boiling point of 76°C-78°C/0.6 torr.