Under nitrogen protection, 6-bromo-8-methoxyquinoline (Intermediate 49, 59.0 g, 248 mmol) was added to 48% hydrobromic acid solution (500 mL). The reaction mixture was stirred at 145 °C for 24 h and subsequently cooled to room temperature. The reaction was quenched with 2 M sodium hydroxide solution and the pH was adjusted to 7. The reaction mixture was extracted with ethyl acetate (3 x 500 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated to dryness under reduced pressure. The residue was purified by solvent recrystallization from petroleum ether/methanol mixture to give 6-bromoquinolin-8-ol (Intermediate 50, 35.0 g, 63% yield) as a brown solid. Mass spectrum (electrospray positive ion mode): [M+H]+ m/z = 224.1. 1H NMR (300 MHz, methanol-d4) δ 7.23 (s, 1H), 7.52-7.59 (m, 2H), 8.21 (d, J = X Hz, 1H), 8.82 (d, J = X Hz, 1H).
