General procedure for the synthesis of 4-bromo-2-hydroxypyridine from 4-bromo-2-methoxypyridine:
Step a: Preparation of 4-bromopyridin-2(1H)-one; To a solution of 1,4-dioxane (26 mL) of 4-bromo-2-methoxypyridine (1.0 g, 5.3 mmol) was added an aqueous 4M HCl solution (13 mL). The reaction mixture was heated at 90 °C for 5 h, followed by heating at 50 °C overnight. Upon completion of the reaction, it was neutralized to pH 8-9 with 1N NaOH solution and extracted with ethyl acetate. The organic phase was dried with anhydrous MgSO4 and concentrated to give 4-bromopyridin-2(1H)-one as a white solid (490 mg, 53% yield). The aqueous phase was concentrated and the residue was stirred with dichloromethane and filtered. The filtrate was concentrated to give additional 4-bromopyridin-2(1H)-one (320 mg, 35% yield).ESI-MS m/z calculated value 173.0, measured value 174.3 (M+1)+. Retention time 0.32 min. 1H NMR (400 MHz, DMSO-d6) δ 11.87 (s, 1H), 7.36 (d, J=7.0 Hz, 1H), 6.64 (d, J=2.0 Hz, 1H), 6.37 (dd, J=2.0,7.0 Hz, 1H).
