Synthesis
Under nitrogen protection, 7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (19 g, 107 mmol) was dissolved in dichloromethane (250 mL) and the solution was cooled to -78 °C. Boron tribromide (1 M solution in dichloromethane, 430 mL, 430 mmol) was slowly added dropwise to this suspension over 1.5 hours. After completion of the dropwise addition, the reaction was maintained for 30 min, followed by removal of the cooling bath to gradually warm the reaction mixture to room temperature and continued stirring overnight. Upon completion of the reaction, the reaction mixture was quenched by careful dropwise addition of methanol (114 mL, 2.81 mol) and the resulting solution was stirred for 1.5 hours. Subsequently, the reaction mixture was concentrated under reduced pressure. The residue was co-evaporated with methanol and crystallized from water, which was filtered, washed with water and dried to afford the target product 3,4-dihydro-7-hydroxy-1(2H)-isoquinolinone (14.6 g, 81% yield). The NMR hydrogen spectrum (300 MHz, DMSO-d6) data of the product were as follows: δH 9.47 (s, 1H), 7.83 (s, 1H), 7.25 (d, J=2.7 Hz, 1H), 7.09 (d, J=8.2 Hz, 1H), 6.85 (dd, J=8.1, 2.7 Hz, 1H), 3.31 (td, J=6.6, 2.8 Hz, 2H), 2.76 (t, J=6.6 Hz, 2H).
References
[1] Journal of Medicinal Chemistry, 1997, vol. 40, # 13, p. 2085 - 2101
[2] Patent: WO2016/198400, 2016, A1. Location in patent: Page/Page column 97
[3] Patent: WO2012/3418, 2012, A2. Location in patent: Page/Page column 53
[4] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 1, p. 222 - 227
[5] Molecules, 2016, vol. 21, # 12,
