Dimethylformamide → 4-Chloro-7-methoxyquinazolin-6-yl acetate

HRID 415018Notes

Reaction equation

HRID 415018 reaction equation
CN(C=O)C.C(Cl)(=O)C([Cl:9])=O.O[C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:27][CH3:28])=[C:20]([O:23][C:24](=[O:26])[CH3:25])[CH:21]=2)[N:16]=[CH:15][N:14]=1>ClCCCl>[Cl:9][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:27][CH3:28])=[C:20]([O:23][C:24](=[O:26])[CH3:25])[CH:21]=2)[N:16]=[CH:15][N:14]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 178486873HCID 178486873, compound

Product 1

HCID 220221604-Chloro-7-methoxyquinazolin-6-yl acetateYield 80.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a stirred solution of anhydrous DMF (4.5 mL) in DCE (20 mL), cooled in an ice-water bath, is added dropwise under nitrogen a solution of oxalyl chloride (7.9 ml, 90 mmol) in DCE (40 mL). A white precipitate forms during the addition. After the end of addition the cold bath is removed and the reaction mixture is stirred at room temperature for 5 min. Acetic acid 4-hydroxy-7-methoxy-quinazolin-6-yl ester (6.5 g, 27.8 mmol) is added in portions via scoopula under nitrogen flow and the mixture is heated immediately to reflux. Heating is continued for 3 hours, followed by cooling to room temperature. The reaction mixture is poured into excess ice:water mixture (100 mL) and extracted with DCM (500 mL). The aqueous layer is further extracted with DCM (2×50 mL). The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure to yield 5.63 g (22.34 mmol, 80%) of desired product as a tan solid.

Workup

  1. additionA white precipitate forms during the addition
  2. additionAfter the end of addition the cold bath
  3. customis removed
  4. temperaturethe mixture is heated immediately
  5. temperatureto reflux
  6. temperatureHeating
  7. waitis continued for 3 hours
  8. temperatureby cooling to room temperature
  9. additionThe reaction mixture is poured into excess ice
  10. extractionwater mixture (100 mL) and extracted with DCM (500 mL)
  11. extractionThe aqueous layer is further extracted with DCM (2×50 mL)
  12. dry with materialThe combined organic extracts are dried (Na2SO4)
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1c2a3d7ffd9e4c24b077aa0c2579a4e3
Source dataset
uspto-grants-2012_01
Patent number
US08088766B2

Reaction notes

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