Phosphorus oxychloride → 2-Chloro-6-methoxyquinoline

HRID 1627679Notes

Reaction equation

HRID 1627679 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8](O)[CH:7]=[CH:6]2.O=P(Cl)(Cl)[Cl:16]>>[Cl:16][C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178488021HCID 178488021, compound

Product 1

HCID 836472-Chloro-6-methoxyquinolineYield 86%

Procedure

A solution of 6-methoxyquinolin-2-ol (400 mg, 2.29 mmol) in POCl3 (5.0 mL) was refluxed for 2 hours. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc (50 mL), the organic layer was washed with saturated NaHCO3 (30 mL×2), dried over Na2SO4, filtered and concentrated to give the crude product, which was purified by silica gel column (PE/EtOAc=10/1) to give 2-chloro-6-methoxyquinoline (380 mg, yield 86%) as a solid. 1H NMR (CDCl3 400 MHz): δ 7.92 (d, J=8.4 Hz, 1H), 7.85 (d, J=9.2 Hz, 1H), 7.32-7.25 (m, 2H), 7.00 (d, J=2.4 Hz, 1H), 3.86 (s, 3H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in EtOAc (50 mL)
  3. washthe organic layer was washed with saturated NaHCO3 (30 mL×2)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas purified by silica gel column (PE/EtOAc=10/1)

Sources & evidence

ORD record
ord-427f7b5e8b8d4211b38d0f5b905d5b6a
Source dataset
uspto-grants-2014_07
Patent number
US08785643B2

Reaction notes

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