Potassium Carbonate → 2-(6-Bromo-7-fluoro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

HRID 519228Notes

Reaction equation

HRID 519228 reaction equation
[Br:1][C:2]1[C:3]([F:13])=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:21]([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>CC(C)=O>[CH2:25]([O:24][C:22](=[O:23])[CH:21]([N:7]1[C:6]2[CH:12]=[C:2]([Br:1])[C:3]([F:13])=[CH:4][C:5]=2[O:10][CH2:9][C:8]1=[O:11])[CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79040Ethyl 2-bromopropionateHCID 235743206-Bromo-7-fluoro-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 867276302-(6-Bromo-7-fluoro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a mixture of 6-bromo-7-fluoro-4H-benzo[1,4]oxazin-3-one (41.0 g, 167 mmol) and K2CO3 (23.0 g, 167 mmol) in acetone (300 mL) was added ethyl 2-bromopropanoate (75.0 g, 53.8 mL, 417 mmol) drop-wise at ambient temperature and the mixture was heated at reflux overnight. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether) to give 2-(6-bromo-7-fluoro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (43.0 g, 75%). 1H NMR (CDCl3, 400 MHz): δ 6.97 (d, J=6.4 Hz, 1H), 6.85 (d, J=8.4 Hz, 1H), 5.25 (q, J=7.2 Hz, 1H), 4.59 (dd, J=15.2 Hz, 2H), 4.27 (m, 2H), 1.63 (d, J=7.2 Hz, 3H), 1.23 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. filtrationfiltered
  4. customThe filtrate was evaporated in vacuo
  5. customthe residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-ccea7a31fa10418d9466a35102b39689
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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