The general procedure for the synthesis of 3-bromo-2-methyl-6-fluoropyridine from 2-amino-5-bromo-6-methylpyridine was as follows: 5-bromo-2-amino-6-methylpyridine (5 g) was dissolved in pyridine hydrogen fluoride (35 mL). The reaction system was cooled to -20°C, followed by the slow addition of potassium nitrite (KNO2, 2.7 g). The reaction was continued by keeping the temperature low. Once the reaction was complete, it was slowly warmed to room temperature and stirred continuously for 4 hours. The reaction mixture was slowly poured into ice water (200 mL) and extracted with a solvent mixture of dichloromethane (50 mL) and ethyl acetate (EtOAc). The organic phases were combined, washed with 1N hydrochloric acid solution and concentrated under reduced pressure to give 5-bromo-2-fluoro-6-methylpyridine (4 g, 78% yield).
