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

HRID 1042860Notes

Reaction equation

HRID 1042860 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.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:27]>C1(C)C=CC=CC=1>[Cl:27][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

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 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's Base (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 the mixture was 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: 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. customthe mixture was azeotroped 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-bd781c4efbf04998807b27275a7aef39
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

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