Lawesson's reagent → 2-(6-Bromo-7-fluoro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

HRID 519229Notes

Reaction equation

HRID 519229 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]([F: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>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]([F:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=[S:30])[CH3:6])[CH3:2]

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 867276302-(6-Bromo-7-fluoro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 867276312-(6-Bromo-7-fluoro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl esterYield 80.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of 2-(6-bromo-7-fluoro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (43.0 g, 124 mmol) in toluene (300 mL) was added Lawesson's reagent (50.6 g, 124 mmol) and the mixture was heated at reflux overnight. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo The residue was purified by chromatography on silica gel (eluting with 5% EtOAc in petroleum ether) to give 2-(6-bromo-7-fluoro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (36.0 g, 80%). 1H NMR (CDCl3, 400 MHz): δ 7.09 (d, J=6.4 Hz, 1H), 6.88 (d, J=8.4 Hz, 1H), 6.62 (brs, 1H), 4.96 (dd, J=15.2 Hz, 2H), 4.23 (m, 2H), 1.72 (d, J=7.2 Hz, 3H), 1.21 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux overnight
  3. customthe solvent was removed in vacuo The residue
  4. customwas purified by chromatography on silica gel (eluting with 5% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-818bb620ef8c4bb590fee264ff1bf4d6
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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