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

HRID 518990Notes

Reaction equation

HRID 518990 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([O:17]C(=O)C)[CH:15]=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[O:21])[CH3:6])[CH3:2].N1CCOCC1>C1COCC1.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:22])[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[O:21])[CH3:6])[CH3:2]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 867273432-(6-Acetoxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 867273442-(6-Hydroxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the crude 2-(6-acetoxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester in THF (80 mL) was added morpholine (5.5 mL, 63 mmol) and the mixture was heated to reflux overnight. The reaction mixture was cooled to ambient temperature and diluted with EtOAc (100 mL). The mixture was washed with brine (30 mL) and the combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatograph on silica gel (eluting with 10% EtOAc in petroleum ether) to give 2-(6-hydroxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as a white solid (3.2 g, 57% over two steps). 1H NMR (CDCl3, 400 MHz): δ 6.88 (d, J=8.8 Hz, 1H), 6.47 (dd, J=2.8 Hz, J=8.8 Hz, 1H), 6.39 (d, J=2.8 Hz, 1H), 5.24 (q, J=6.8 Hz, 1H), 4.54 (d, J=14.8 Hz, 2H), 4.20 (q, J=7.2 Hz, 2H), 1.62 (d, J=6.8 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H). The phenol OH was not observed in CDCl3.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux overnight
  3. washThe mixture was washed with brine (30 mL)
  4. dry with materialthe combined organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatograph on silica gel (eluting with 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-f0284ad4abf242ab9998bcbc88ff8e4e
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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