Phosphorus oxychloride → 2-Chloro-3-fluoro-7-methoxyquinoline

HRID 339092Notes

Reaction equation

HRID 339092 reaction equation
[F:1][C:2]1[C:3](=O)[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:3]1[C:2]([F:1])=[CH:11][C:10]2[C:5](=[CH:6][C:7]([O:12][CH3:13])=[CH:8][CH:9]=2)[N:4]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 152605803-fluoro-7-methoxyquinolin-2(1H)-one

Product 1

HCID 220305912-Chloro-3-fluoro-7-methoxyquinolineYield 36%

Procedure

A mixture of 3-fluoro-7-methoxyquinolin-2(1H)-one (1.40 g, 7.25 mmol) and POCl3 (13.3 ml, 145 mmol) was stirred at 110 C (bath) for 1 hour. The POCl3 was removed under reduced pressure. Ethyl acetate (30 mL) and saturated sodium bicarbonate (30 mL) were added and stirred for 10 minutes. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (10:1 hexane/ethyl acetate) to give 2-chloro-3-fluoro-7-methoxyquinoline (0.55 g, 2.60 mmol, 36% yield) as white solid.

Workup

  1. customThe POCl3 was removed under reduced pressure
  2. additionEthyl acetate (30 mL) and saturated sodium bicarbonate (30 mL) were added
  3. stirringstirred for 10 minutes
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified by flash chromatography on silica gel (10:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-dbda6865454944e5a0060a862a7bbe18
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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