Phosphorus oxychloride → 4-Chloro-2-(trifluoromethyl)quinazoline

HRID 2063588Notes

Reaction equation

HRID 2063588 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[NH:12][C:11](=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.P(Cl)(Cl)([Cl:18])=O>CN(C=O)C>[Cl:18][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]([C:2]([F:15])([F:14])[F:1])[N:12]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1354155312-(Trifluoromethyl)-3,4-dihydroquinazolin-4-one

Product 1

HCID 14754354-Chloro-2-(trifluoromethyl)quinazolineYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2-(trifluoromethyl)quinazolin-4(3H)-one (12 g) and phosphorous oxychloride (100 ml) was added DMF (0.5 ml) and the mixture was refluxed under nitrogen for 16 h. The excess phosphorous oxychloride was distilled off and the residue was diluted with ethyl acetate (200 ml). The ethyl acetate layer was washed with 10% solution of sodium bicarbonate, water and brine. The solvent was dried and evaporated. The residue was purified by chromatography (silica gel: 60-120 mesh) eluting with pet ether/ethyl acetate (9/1) to afford 8 g (61%) of the titled compound as a pale yellow solid.

Workup

  1. temperaturethe mixture was refluxed under nitrogen for 16 h
  2. distillationThe excess phosphorous oxychloride was distilled off
  3. additionthe residue was diluted with ethyl acetate (200 ml)
  4. washThe ethyl acetate layer was washed with 10% solution of sodium bicarbonate, water and brine
  5. customThe solvent was dried
  6. customevaporated
  7. customThe residue was purified by chromatography (silica gel: 60-120 mesh)
  8. washeluting with pet ether/ethyl acetate (9/1)

Sources & evidence

ORD record
ord-7aa8859819484aabb5db4fc2ec541806
Source dataset
uspto-grants-2012_10
Patent number
US08288398B2

Reaction notes

Loading…