Potassium Carbonate → 2-(6-Bromo-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Temperature

70 °C

To a suspension of 6-bromo-4H-benzo[1,4]oxazin-3-one (27 g, 118.4 mmol) and K2CO3 (49.1 g, 355.2 mmol) in acetone (200 mL) was added 2-bromo-propionic acid ethyl ester (32.1 g, 177.6 mmol) and the reaction mixture was heated at 70° C. for 5 h. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo and the residue was dissolved in DCM (50 mL). The organic phase was washed with water (3×20 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was evaporated to dryness and the residue was purified by chromatography on silica gel (eluting with 5% EtOAc in petroleum ether) to give 2-(6-bromo-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as a colorless liquid (32.5 g, 100 mmol, 84%). 1H NMR (CDCl3, 400 MHz): δ 7.09 (dd, J=8 Hz, J=2 Hz, 1H), 6.94 (d, J=2.0 Hz, 1H), 6.90 (d, J=8.4 Hz, 1H), 5.28 (q, J=14.8 Hz, 1H), 5.21 (q, J=5.4 Hz, 1H), 4.55 (d, J=15.2 Hz, 2H), 4.17 (m, 1H), 1.63 (d, J=1.2 Hz, 3H), 1.22 (t, J=1.2 Hz, 3H).

1. temperatureThe reaction mixture was cooled to ambient temperature
2. customthe solvent was removed in vacuo
3. dissolutionthe residue was dissolved in DCM (50 mL)
4. washThe organic phase was washed with water (3×20 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationAfter filtration
7. customthe filtrate was evaporated to dryness
8. customthe residue was purified by chromatography on silica gel (eluting with 5% EtOAc in petroleum ether)

ORD record

ord-c37462ea741f459797b977c049bb30a7

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115151B2