Acetonitrile → 7-Bromo-4-chloro-6-fluoroquinoline

HRID 1473512Notes

Reaction equation

HRID 1473512 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](O)=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[F:13].C(#N)C.P(Cl)(Cl)([Cl:19])=O>C(OCC)(=O)C>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:19])=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[F:13]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 24813Phosphorus oxychlorideHCID 178516369HCID 178516369, compound

Product 1

HCID 866875667-Bromo-4-chloro-6-fluoroquinolineYield 28.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A vial was charged with 7-bromo-6-fluoroquinolin-4-ol (0.460 g, 1.900 mmol) and acetonitrile (9.50 ml). Phosphoryl trichloride (0.354 ml, 3.80 mmol) was then added, and the reaction was stirred for 2 h at 90° C. The reaction was diluted with ethyl acetate and washed with water. The aqueous was extracted once more with ethyl acetate, and the combined organics were dried over sodium sulfate, filtered and concentrated in vacuo. The material was then purified via silica gel chromatography eluting with 0-75% ethyl acetate in heptanes to yield 7-bromo-4-chloro-6-fluoroquinoline (0.141 g, 0.541 mmol, 28.5% yield) as a white solid. m/z (ESI) 260.1 (M+H)+.

Workup

  1. washwashed with water
  2. extractionThe aqueous was extracted once more with ethyl acetate
  3. dry with materialthe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe material was then purified via silica gel chromatography
  7. washeluting with 0-75% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-e39c3ea282a648d2b6a1481f97a12130
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…