Phosphorus oxychloride → 4-Chloro-5,7-dimethoxyquinoline

HRID 1013710Notes

Reaction equation

HRID 1013710 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](O)=[CH:6][CH:7]=[N:8]2.O=P(Cl)(Cl)[Cl:18]>C1(C)C=CC=CC=1>[Cl:18][C:5]1[C:4]2[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=2[O:2][CH3:1])[N:8]=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178493398HCID 178493398, compound

Product 1

HCID 178804724-Chloro-5,7-dimethoxyquinoline

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of crude 5,7-dimethoxyquinolin-4-ol (5.36 g, 26 mmol) and Hunig'sBase (9.1 ml, 52 mmol) in toluene, was added POCl3(29 ml, 313 mmol). The mixture was refluxed for 5 h. Excess POCl3 was removed under reduced pressure and azeotroped with toluene. The resultant gum was treated with sat. NaHCO3 until no gas generated. The mixture was extracted with EtOAc, the organic extracts were combined and washed with sodium bicarbonate and solvent removed under reduced pressure. The crude product was purified via column chromatography on silica gel (RediSep 120 g column, gradient elution with 0-50% EtOAc/DCM) to afford 4-chloro-5,7-dimethoxyquinoline as a yellow solid. MS Found m/z=[M+H]+. 224.2 Calc'd for C11H10ClN: 223.7.

Workup

  1. temperatureThe mixture was refluxed for 5 h
  2. customExcess POCl3 was removed under reduced pressure
  3. customazeotroped with toluene
  4. additionThe resultant gum was treated with sat. NaHCO3 until no gas
  5. extractionThe mixture was extracted with EtOAc
  6. washwashed with sodium bicarbonate and solvent
  7. customremoved under reduced pressure
  8. customThe crude product was purified via column chromatography on silica gel (RediSep 120 g column, gradient elution with 0-50% EtOAc/DCM)

Sources & evidence

ORD record
ord-da56e637f03248c59a005a2723f3670a
Source dataset
uspto-grants-2011_07
Patent number
US07981891B2

Reaction notes

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