Water → 7-(Benzyloxy)-4-chloro-6-methoxyquinoline

HRID 2106111Notes

Reaction equation

HRID 2106111 reaction equation
[CH3:1]N(C=O)C.C(Cl)(=O)C(Cl)=O.[CH2:12]([O:19][C:20]1[CH:29]=[C:28]2[C:23](C(=O)N[CH:26]=[N:27]2)=[CH:22][C:21]=1[O:31][CH3:32])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.O.[CH:34]([Cl:37])(Cl)Cl>C(Cl)Cl>[CH2:12]([O:19][C:20]1[CH:29]=[C:28]2[C:23]([C:34]([Cl:37])=[CH:1][CH:26]=[N:27]2)=[CH:22][C:21]=1[O:31][CH3:32])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6212Chloroform2×HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 1354047187-Benzyloxy-6-methoxy-3H-quinazolin-4-one

Product 1

HCID 226465627-(Benzyloxy)-4-chloro-6-methoxyquinolineYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Dry DMF (8.0 ml, 103 mmol) was dissolved in dry CHCl3 (40 ml) and cooled in an ice bath. Oxalyl chloride (9.0 ml, 105 mmol) in CH2Cl2 (10 ml) was added dropwise with stirring at 0° C. When the bubbling had ceased, this solution was added slowly to an ice-cold solution of 7-benzyloxy-6-methoxy-3H-quinazolin-4-one (10.0 g, 35.4 mmol) in dry CHCl3 (60 ml) and the mixture was then heated to reflux for 2-3 hrs. After cooling to room temperature, H2O (100 ml) was added and the phases were separated. The aqueous phase was further extracted with CHCl3 (2×). The combined CHCl3 extractions were washed with sat'd NaCl (1×), dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by flash chromatography (1:1 hexanes:EtOAc, followed by 100% EtOAc) to give 7-benzyloxy-4-chloro-6-methoxy-quinoline (5.11 g, 48%). LC/MS Calcd for [M+H]+ 301.1, found 301.1.

Workup

  1. temperaturecooled in an ice bath
  2. temperaturethe mixture was then heated
  3. temperatureto reflux for 2-3 hrs
  4. temperatureAfter cooling to room temperature
  5. customthe phases were separated
  6. extractionThe aqueous phase was further extracted with CHCl3 (2×)
  7. extractionThe combined CHCl3 extractions
  8. washwere washed with sat'd NaCl (1×)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customThe resulting residue was purified by flash chromatography (1:1 hexanes:EtOAc, followed by 100% EtOAc)

Sources & evidence

ORD record
ord-b72ab89415dd486388a460816cf74e04
Source dataset
uspto-grants-2009_08
Patent number
US07579473B2

Reaction notes

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