Sodium hydride → 7-Bromo-3,4-dihydro-1-benzoxepin-5(2H)-one

Temperature

0 °C

1-(5-bromo-2-(2-bromoethoxy)phenyl)ethanone from step H (9.0 g, 28.0 mmol) was dissolved in THF (175 mL), cooled to 0° C. and treated with sodium hydride (0.805 g, 33.5 mmol). The reaction mixture was carefully heated to reflux and continued heating for 20 h. The crude mixture was cooled, quenched with 2 M HCl (50 mL) and partitioned between brine (300 mL) and EtOAc (250 mL). The organic layer was dried over sodium sulfate, concentrated in vacuo and purified by silica gel column chromatography (10-30% EtOAc/hexanes). The clean fractions were concentrated in vacuo to afford 7-bromo-3,4-dihydrobenzo[b]oxepin-5(2H)-one (5.41 g, 22.4 mmol, 80% yield) as a colorless oil. LCMS (M+H)+=242.95. 1H NMR (500 MHz, chloroform-d) δ 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. temperatureThe reaction mixture was carefully heated
2. temperatureto reflux
3. temperaturecontinued heating for 20 h
4. customquenched with 2 M HCl (50 mL)
5. custompartitioned between brine (300 mL) and EtOAc (250 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. concentrationconcentrated in vacuo
8. custompurified by silica gel column chromatography (10-30% EtOAc/hexanes)
9. concentrationThe clean fractions were concentrated in vacuo

ORD record

ord-c9996f42e95b4a98b64bc70e82db6ef7

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604024B2