Dimethyl Carbonate → HCID 71060952, compound

To a solution of 7-bromo-3,4-dihydrobenzo[b]oxepin-5(2H)-one from step H2 (5.41 g, 22.4 mmol) in dimethyl carbonate (28.3 ml, 337 mmol) was slowly added a sodium hydride dispersion in mineral oil (2.69 g, 112 mmol). The mixture was stirred at rt for 15 min, then at 80° C. for 2 h. The mixture was then cooled to rt and stirred for 16 h. The mixture was concentrated in vacuo and diethyl ether (150 mL) of was added. The organic layer was washed with of 1 N HCl (100 mL) followed by water, and dried over sodium sulfate. The solvent was removed in vacuo. The crude product was purified by silica-gel column chromatography (10-40% EtOAc/hexanes, linear gradient) to afford methyl 7-bromo-5-oxo-2,3,4,5-tetrahydrobenzo[b]oxepine-4-carboxylate (3.32 g, 11.1 mmol, 50% yield) as a white solid. LCMS (M+H)+=300.95. 1H NMR (500 MHz, chloroform-d) δ 7.91 (d, J=2.4 Hz, 1H), 7.61-7.48 (m, 1H), 7.03-6.89 (m, 1H), 4.49 (ddd, J=12.4, 6.7, 3.9 Hz, 1H), 4.15-4.03 (m, 2H), 3.77 (s, 3H), 2.68-2.47 (m, 2H).

1. waitat 80° C. for 2 h
2. temperatureThe mixture was then cooled to rt
3. stirringstirred for 16 h
4. concentrationThe mixture was concentrated in vacuo and diethyl ether (150 mL)
5. additionof was added
6. washThe organic layer was washed with of 1 N HCl (100 mL)
7. dry with materialdried over sodium sulfate
8. customThe solvent was removed in vacuo
9. customThe crude product was purified by silica-gel column chromatography (10-40% EtOAc/hexanes, linear gradient)

ORD record

ord-aaa35d72872d428da7ded2231b4c6329

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604024B2