4-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline → 4-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamine

HRID 720961Notes

Reaction equation

HRID 720961 reaction equation
[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:17][CH3:18])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.[H][H]>C(OCC)(=O)C.CN(C)C=O.C(N(CC)CC)C.[OH-].[Pd+2].[OH-]>[CH3:16][O:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[O:17][CH3:18])[N:8]=[CH:7][CH:6]=[C:5]2[O:4][C:3]1[CH:19]=[CH:20][C:21]([NH2:23])=[CH:22][C:2]=1[F:1]

Participants

5

Reactant 2

HCID 114507634-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxyquinolineHCID 178418361HCID 178418361, compound

Product 1

HCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamine

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 86593454ethyl acetate N,N-dimethylformamide triethylamineSolvent

Procedure

4-Chloro-6,7-dimethoxyquinazoline (10.23 g) and 2-fluoro-4-nitrophenol (14.37 g) were suspended in monochlorobenzene (100 ml), and the suspension was heated under reflux overnight. The solvent was removed by distillation under the reduced pressure, and the residue was washed with toluene, was filtered, and was dried. The crystal thus obtained was then suspended in an aqueous sodium hydroxide solution, and the suspension was filtered, followed by drying to give 4-(3-fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline (14.2 g, yield 90%). 4-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxy-quinoline (4.57 g) was dissolved in ethyl acetate/N,N-dimethylformamide/triethylamine (100 ml/100 ml/20 ml) to prepare a solution. Palladium hydroxide (1.2 g) was added to the solution, and the mixture was stirred in a hydrogen atmosphere at room temperature overnight. After filtration through Celite, the solvent was removed by distillation under the reduced pressure. A saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure to quantitatively give 4.27 g of the title compound.

Workup

  1. customto prepare a solution
  2. filtrationAfter filtration through Celite
  3. customthe solvent was removed by distillation under the reduced pressure
  4. additionA saturated aqueous sodium hydrogencarbonate solution was added to the residue
  5. extractionthe mixture was extracted with chloroform
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. customThe solvent was removed by distillation under the reduced pressure to quantitatively give 4.27 g of the title compound

Sources & evidence

ORD record
ord-c02a62a8a64b4389b730f75ada96520c
Source dataset
uspto-grants-2006_11
Patent number
US07135466B2

Reaction notes

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