Phosphorus oxychloride → 4-Chloro-7-fluoro-6-methoxy-3-quinolinecarbonitrile

HRID 1837330Notes

Reaction equation

HRID 1837330 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[C:7]([C:12]#[N:13])=[CH:8][NH:9]2)=[CH:4][C:3]=1[O:15][CH3:16].P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:6]1[C:5]2[C:10](=[CH:11][C:2]([F:1])=[C:3]([O:15][CH3:16])[CH:4]=2)[N:9]=[CH:8][C:7]=1[C:12]#[N:13]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 121507027-FLUORO-6-METHOXY-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBONITRILE

Product 1

HCID 121507034-Chloro-7-fluoro-6-methoxy-3-quinolinecarbonitrileYield 58.1%

Procedure

A mixture of 7-fluoro-6-methoxy-4-oxo-1,4-dihydro-3-quinolinecarbonitrile (1.0 g, 4.59 mmol) and 14 g of phosphorous oxychloride is heated at reflux for 30 minutes then concentrated in vacuo. The residue is partitioned between aqueous sodium bicarbonate and ethyl acetate. The organic layer is dried over magnesium sulfate, filtered and concentrated on to silica gel. Purification by flash column chromatography eluting with a gradient of 1:5 ethyl acetate:hexane to 1:1 ethyl acetate:hexane, provides 631 mg of 4-chloro-7-fluoro-6-methoxy-3-quinolinecarbonitrile, mp 160-162° C.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 30 minutes
  3. concentrationthen concentrated in vacuo
  4. customThe residue is partitioned between aqueous sodium bicarbonate and ethyl acetate
  5. dry with materialThe organic layer is dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated on to silica gel
  8. customPurification by flash column chromatography
  9. washeluting with a gradient of 1:5 ethyl acetate

Sources & evidence

ORD record
ord-1d773e79593c4038aa9ab701fe56b3d3
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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