In a dry 500 mL three-necked round-bottomed flask equipped with a reflux condenser and a charging funnel, BH3-THF solution (160 mL) and anhydrous THF (50 mL) were added. The mixture was cooled to 0 °C. A solution of anhydrous THF (100 mL) of 5-bromo-1H-isoindole-1,3(2H)-dione (8.0 g, 35.4 mmol) was slowly added dropwise to the cooled mixture, followed by allowing the reaction system to slowly warm up to room temperature. After 10 minutes of reaction, the mixture was heated to reflux for 16 hours. Upon completion of the reaction, the mixture was cooled to 0°C and the reaction was quenched by careful addition of methanol (note: violent foaming may occur). Next, 20-30 mL of 2N HCl was added and the mixture was refluxed for 1 hour. After cooling, the reaction mixture was alkalized with NaOH solution and subsequently extracted with ethyl acetate. The organic phases were combined, washed sequentially with water and saturated NaCl solution, dried with Na2SO4 and concentrated under reduced pressure. The crude product was dissolved in MeOH (150 mL), Et3N (12 mL) and di-tert-butyl dicarbonate (13.8 g, 63.23 mmol) were added, and stirred at room temperature for 16 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The crude product was diluted with CH2Cl2 (200 mL), washed sequentially with water and saturated NaCl solution, and dried with Na2SO4. The crude product was purified by column chromatography using a hexane solution of 20% ethyl acetate as eluent to give a colorless solid. The solid was dissolved in dioxane, HCl was added and stirred at room temperature for 10 min, the resulting solid was filtered and dried to give 5-bromoisodihydroindole hydrochloride (3.0 g, 42.8%) as a gray solid.
