3-Amino-2-bromo-6-methylpyridine or 4-amino-2-bromo-6-methylpyridine (25.20 g, 134.73 mmol) was added to a mixture of water (78.1 mL) and conc. HCl (12.8 mL, 350.30 mmol), and then the mixture was cooled to 0 ℃. To it, sodium nitrite (18.6 g,269.46 mmol) was added portion-wise with stirring over 20 min while keeping the reaction temperature between –5 ℃and 0 ℃. After 10 min, 65 per cent hexafluorophosphoric acid solution (43.26 g, 296.41 mmol) was added dropwise with cooling, at which point many precipitates were formed. The precipitates were collected by filtration using a glass filter funnel, washed with cold water (2 × 50 mL) and diethyl ether (100 mL), and then dried in the air for 48 h. The solid was slowly heated to 100 ℃ (very exothermic), and a dark, oily material was formed after 10 min. The oil was basified with diluted NaOH solution to pH~10 and extracted with CH2Cl2 (2 × 150 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The residue was purified by MPLC on neutral alumina using hexane/EtOAc (10:1) as an eluent to afford 2-Bromo-3-fluoro-6-picoline.
[1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 22, p. 5228 - 5231
