Phosphorus oxychloride → 4-Chloro-6,7-dimethoxyquinazoline

HRID 1375780Notes

Reaction equation

HRID 1375780 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH3:19])[N:14]=[CH:13][NH:12][C:11]2=O>S1(CCCC1)(=O)=O>[Cl:3][C:11]1[C:10]2[C:15](=[CH:16][C:17]([O:18][CH3:19])=[C:8]([O:7][CH3:6])[CH:9]=2)[N:14]=[CH:13][N:12]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1354950166,7-Dimethoxy-3H-quinazolin-4-one

Product 1

HCID 27693644-Chloro-6,7-dimethoxyquinazolineYield 71.4%

Reagents, catalysts & solvents 1

HCID 31347SulfolaneSolvent

Conditions

Temperature
120 °C

Procedure

Sulfolane (250 ml) and phosphorus oxychloride (250 ml=412.5 g, 2.69 mol) were added to 6,7-dimethoxy-4-quinazolone (50.1 g, 0.24 mol), and the mixture was stirred at 120° C. for one hr. The reaction mixture was cooled to room temperature, and the excess phosphorus oxychloride was then removed by distillation under the reduced pressure. The residue was poured into ice water (1000 ml), and chloroform (1000 ml) was added thereto. The aqueous layer was adjusted to pH 6.5 by the addition of a 20% sodium hydroxide solution, followed by the separation of the organic layer from the aqueous layer. The separated organic layer was washed with water (1000 ml×six times), was dried over sodium sulfate, and was then concentrated under the reduced pressure. Tetrahydrofuran (470 ml) was added to the residue, and the mixture was refluxed. The reaction solution was cooled to −5° C. to −10° C. and was filtered and dried to give 38.5 g (yield 71.4%) of the target product.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe excess phosphorus oxychloride was then removed by distillation under the reduced pressure
  3. additionThe residue was poured into ice water (1000 ml), and chloroform (1000 ml)
  4. additionwas added
  5. additionThe aqueous layer was adjusted to pH 6.5 by the addition of a 20% sodium hydroxide solution
  6. customfollowed by the separation of the organic layer from the aqueous layer
  7. washThe separated organic layer was washed with water (1000 ml×six times)
  8. dry with materialwas dried over sodium sulfate
  9. concentrationwas then concentrated under the reduced pressure
  10. additionTetrahydrofuran (470 ml) was added to the residue
  11. temperaturethe mixture was refluxed
  12. temperatureThe reaction solution was cooled to −5° C. to −10° C.
  13. filtrationwas filtered
  14. customdried

Sources & evidence

ORD record
ord-eff7c5bd1de14262978355a9895cbdb2
Source dataset
uspto-grants-2007_01
Patent number
US07169789B2

Reaction notes

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