2-Bromo-3-(bromomethyl)pyridine

3430-17-9

94446-97-6

General procedure for the synthesis of 2-bromo-3-(bromomethyl)pyridine from 2-bromo-3-methylpyridine: The intermediate was prepared by a modification of the method based on that disclosed by Rebek, J., et al. in J. Am. Chem. Soc., 107, 7487 (1985). A three-necked round-bottomed flask equipped with a stirring bar was flame dried, vacuum cooled and purged with nitrogen. To the flask were added 2-bromo-3-methylpyridine (5.2 mL, 29.1 mmol), N-bromosuccinimide (5.5 g, 32.0 mmol) and degassed benzene (126 mL). The flask was equipped with a condenser, heated to 40 °C and AIBN (0.24 g, 1.5 mmol) was added in batches. The reaction mixture was stirred at 40 °C and irradiated using a sun lamp. The reaction progress was monitored by TLC and HPLC and stopped when the conversion of pyridine reagent reached 80% (about 8 h). The reaction mixture was concentrated under reduced pressure and then redissolved in a 4:1 solvent mixture of dichloromethane/ethyl acetate (120 mL) and extracted sequentially with 50 mL each of saturated aqueous sodium bicarbonate, water and saturated aqueous sodium chloride. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. After standing, the residue was not completely soluble in dichloromethane and the resulting suspension was filtered to remove insoluble solids. The filtrate was concentrated to near dryness and the residue was purified by normal phase fast chromatography (ethyl acetate/hexane) to afford 2-bromo-3-(bromomethyl)pyridine (3.0 g, 11.9 mmol, 41%) as a yellow solid.1H NMR (400 MHz, CDCl3) δ 8.33 (1H, dd, J=5, 2 Hz), 7.78 (1H, dd, J=7 , 2 Hz), 7.28 (1H, dd, J=5, 4 Hz), 4.57 (2H, s).MS (LC/MS) m/z Observed 249.97, Expected 249.89 [M+H]+.