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

HRID 518973Notes

Reaction equation

HRID 518973 reaction equation
[F:1][C:2]1[C:12]([N+:13]([O-:15])=[O:14])=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH:23]([CH3:29])[C:24]([O:26][CH2:27][CH3:28])=[O:25]>CC(C)=O>[CH2:27]([O:26][C:24](=[O:25])[CH:23]([N:6]1[C:5]2[CH:11]=[C:12]([N+:13]([O-:15])=[O:14])[C:2]([F:1])=[CH:3][C:4]=2[O:9][CH2:8][C:7]1=[O:10])[CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79040Ethyl 2-bromopropionateHCID 137312977-Fluoro-6-nitro-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 867273232-(7-Fluoro-6-nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

A suspension of 7-fluoro-6-nitro-4H-benzo[1,4]oxazin-3-one (3.50 g, 16.50 mmol) and K2CO3 (3.42 g, 24.75 mmol) in acetone (100 mL) was stirred at rt for 15 min. A solution of ethyl 2-bromopropanoate (5.97 g, 33.0 mmol) in acetone (60 mL) was added dropwise and the reaction mixture was heated at reflux for 5 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was dissolved in DCM (50 mL) and washed with water (50 mL). The organic phase was separated and dried over anhydrous Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 0-30% EtOAc in petroleum ether) to give 2-(7-fluoro-6-nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as a white solid (3.29 g, 64%). 1H NMR (DMSO-d6, 400 MHz): δ 7.89 (d, J=7.2 Hz, 1H), 7.39 (d, J=11.6 Hz, 1H), 5.28 (q, J=7.2 Hz 1H), 4.86 (s, 2H), 4.02-4.16 (m, 2H), 1.48 (d, J=7.2 Hz, 3H), 1.12 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 5 h
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in DCM (50 mL)
  6. washwashed with water (50 mL)
  7. customThe organic phase was separated
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated in vacuo
  11. customThe residue was purified by column chromatography on silica gel (eluting with 0-30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-3dd5463a067d41729faa62921e7aa588
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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