Step 4: To a solution of dichloromethane (DCM, 75 mL) containing 5-bromo-7-fluoro-1-indanone (144d, 10.35 g, 45.19 mmol) was slowly added methanesulfonic acid (52.73 mL, 70.92 g, 737.90 mmol), followed by batchwise addition of sodium azide (5.88 g, 90.44 mmol), at 0 °C. The reaction mixture was stirred continuously at 0 °C for 2 hours. Upon completion of the reaction, the reaction was quenched by the addition of 20% aqueous sodium hydroxide solution (40 mL) and stirring was continued for 30 min. The aqueous phase was extracted with dichloromethane (DCM, 400 mL x 3) and the organic layers were combined. The organic layer was washed sequentially with saturated brine (200 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate=10/1 to 2/1) to afford 6-bromo-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one (144e, 5.2 g, 47.1% yield). The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.22-7.25 (d, J=10.4 Hz, 1H), 7.20 (s, 1H), 6.94 (s, 1H), 3.46-3.53 (m, 2H), 2.88-2.97 (m, 2H); MS-ESI [M+H]+=243.9/245.9.
