2-Bromo-5-methylpyridine

• 5,5′-dimethyl-2,2′-bipyridine
• 5-methyl-2,2′:6′,2″-terpyridine
• 5-bromo-5″-methyl-2,2′:6′,2″-terpyridine

1603-41-4

3510-66-5

General procedure for the synthesis of 2-bromo-5-methylpyridine from 2-amino-5-methylpyridine: Method B Intermediate 7: 2-[[6-morpholin-4-yl]-pyridin-3-yl]ethylamine Step 1: Synthesis of 2-bromo-5-methylpyridine To a stirred 1.5 L 48% hydrobromic acid solution of 2-amino-5-methylpyridine (120 g, 1.10 mol), bromine (160 mL, 498 g, 3.11 mol) was slowly added over a period of 1 h at -20 °C. The addition of bromine (160 mL, 498 g, 3.11 mol) to a stirred solution of 2-amino-5-methylpyridine was completed at -20 °C. After addition, stirring was continued at the same temperature for 2 hours. Subsequently, a solution of sodium nitrite (204 g, 2.95 mol) in 300 mL of water was slowly added to the reaction mixture and stirred at -20 °C for an additional 1 hour. Upon completion of the reaction, the reaction mixture was quenched to -20 °C with aqueous sodium hydroxide (2 kg NaOH dissolved in 2 L of water) and then extracted with ether (3 x 1 L). The organic layers were combined, washed sequentially with water and brine, dried over anhydrous sodium sulfate and concentrated to give the crude product. The crude product was purified by distillation (bath temperature 130 °C, vacuum temperature 85-90 °C, vacuum 0.01 mmHg) to give 172 g of 2-bromo-5-methylpyridine as an off-white low melting point solid in 90% yield. [TLC detection, Rf = 0.8, unfolding agent: ether]