Water → 2-(6-Bromo-7-methyl-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

HRID 519222Notes

Reaction equation

HRID 519222 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([Br:18])[C:15]([CH3:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=O)[CH3:6])[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:30])=CC=1.O>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([Br:18])[C:15]([CH3:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[S:30])[CH3:6])[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 87949Lawesson's reagentHCID 86727626(6-Bromo-7-methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 867276272-(6-Bromo-7-methyl-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl esterYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 2-(6-bromo-7-methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (23.6 g, 69 mmol) in toluene (300 mL) was added Lawesson's reagent (30.7 g, 76 mmol) and the reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature water (300 mL) was added. The organic phase was separated and the aqueous portion was extracted with EtOAc (3×100 mL). The combined organic phase was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 5% EtOAc in petroleum ether) to give 2-(6-bromo-7-methyl-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as solid (20.0 g, 81%). 1H NMR (DMSO-d6, 400 MHz): δ 7.41 (s, 1H), 7.16 (s, 1H), 6.03 (m, 1H), 4.90 (s, 2H), 4.14 (m, 2H), 2.29 (s, 3H), 1.61 (d, J=6.8 Hz, 3H), 1.08 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 4 h
  3. additionwas added
  4. customThe organic phase was separated
  5. extractionthe aqueous portion was extracted with EtOAc (3×100 mL)
  6. washThe combined organic phase was washed with brine (100 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography on silica gel (eluting with 5% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-5474646d958044a1ab2e65f522e43fe5
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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