55580-08-0

Step H2: 1-[5-Bromo-2-(2-bromoethoxy)phenyl]ethanone (9.0 g, 28.0 mmol) was dissolved in THF (175 mL) and cooled to 0 °C. Under stirring, sodium hydride (0.805 g, 33.5 mmol) was slowly added. The reaction mixture was carefully heated to reflux and maintained at reflux for 20 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the reaction was quenched with 2 M HCl (50 mL). The mixture was transferred to a partition funnel and extracted by adding brine (300 mL) and EtOAc (250 mL). The organic layer was separated, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with an eluent gradient of 10-30% EtOAc/hexane. The pure grades were collected and concentrated under reduced pressure to afford 7-bromo-3,4-dihydro-2H-benzo[B]oxepan-5-one (5.41 g, 22.4 mmol, 80% yield) as a colorless oil.LCMS (M + H)+ = 242.95.1H NMR (500 MHz, CDCl3) δ 7.91-7.85 (m, 1H), 7.54-7.48 (m, 1H), 7.91-7.85 (m, 1H). 7.54-7.48 (m, 1H), 6.98 (d, J = 8.5 Hz, 1H), 4.25 (t, J = 6.6 Hz, 2H), 2.91 (t, J = 6.9 Hz, 2H), 2.23 (quin, J = 6.8 Hz, 2H).

[1] Patent: WO2012/162330, 2012, A1. Location in patent: Page/Page column 41-42
[2] Patent: US2009/247567, 2009, A1. Location in patent: Page/Page column 183
[3] Patent: US2011/76291, 2011, A1. Location in patent: Page/Page column 144-145
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 2, p. 627 - 640