Synthesis
5-Bromo-2-chloro-3-methoxypyridine (36 g, 162 mmol) was used as the raw material, which was dissolved in hydrobromic acid (200 mL, 3683 mmol) and the reaction was stirred at 100 °C for 48 hours. Upon completion of the reaction, the reaction mixture was concentrated and the pH was adjusted to alkaline with saturated NaHCO3 solution, followed by extraction with EtOAc (600 mL x 2). The organic phases were combined, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/EtOAc, 10:1). All fractions that were shown to contain the target product by TLC (unfolding agent: petroleum ether/EtOAc, 2:1, Rf=0.6) were collected, combined and concentrated to give 5-bromo-2-chloropyridin-3-ol (21 g, 86 mmol, 52.9% yield) as a light yellow oil.1H NMR (400 MHz, methanol-d4) δ 7.96 (t, J=2.0 Hz, 1H), 7.47 (d, J=2.4 Hz, 1H).ESI-LCMS m/z 208.0, 210.0 ([M+H]+).
