Morpholine → HCID 86727385, compound

HRID 519025Notes

Reaction equation

HRID 519025 reaction equation
C([O:4][C:5]1[C:22]([F:23])=[CH:21][C:8]2[O:9][CH2:10][C:11](=[O:20])[N:12]([CH:13]([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:7]=2[CH:6]=1)(=O)C.N1CCOCC1>C1COCC1>[F:23][C:22]1[C:5]([OH:4])=[CH:6][C:7]2[N:12]([CH:13]([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:11](=[O:20])[CH2:10][O:9][C:8]=2[CH:21]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 86727384HCID 86727384, compound

Product 1

HCID 86727385HCID 86727385, compoundYield 97.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-(6-acetoxy-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)propanoate (13 g, 40.0 mmol) in THF (100 mL) was added morpholine (10.4 mL, 120 mmol) and the reaction mixture was heated at reflux for 18 h. The reaction mixture was cooled to ambient temperature, filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 5% EtOAc in petroleum ether) to give ethyl 2-(7-fluoro-6-hydroxy-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)propanoate (11 g, 80%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 6.78 (d, J=10.4 Hz, 1H), 6.49 (d, J=8.4 Hz, 1H), 5.20 (m, 2H), 4.57 (q, J=14.8 Hz, 2H), 4.20 (m, 2H), 1.58 (d, J=7.2 Hz, 3H), 1.19 (t, 3H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel (eluting with 5% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-f48f52286be24522ab3db1c882fa4838
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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