Hydrochloric Acid → 6,7-Difluoro-2-methylquinoline

HRID 892155Notes

Reaction equation

HRID 892155 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl[C:11]1[C:16](=O)C(Cl)=C(Cl)[C:13](=O)[C:12]=1Cl.Cl.C(=O)/C=C/C>CC(O)CC>[CH3:13][C:12]1[CH:11]=[CH:16][C:6]2[C:4](=[CH:3][C:2]([F:1])=[C:8]([F:9])[CH:7]=2)[N:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8371ChloranilHCID 774693,4-DifluoroanilineHCID 447466Crotonaldehyde

Product 1

HCID 222413776,7-Difluoro-2-methylquinoline

Reagents, catalysts & solvents 1

HCID 6568(+-)-2-ButanolSolvent

Conditions

Temperature
50 °C

Procedure

To a refluxing solution of 3,4-difluoroaniline (2.30 ml, 23.2 mmoles), tetrachloro-1,4-benzoquinone (5.70 g, 23.2 mmoles), and concentrated hydrochloric acid (6 ml) in 2-butanol (40 ml) is added crotonaldehyde (1.92 ml, 23.2 mmoles). After 2.5 hours the reaction mixture is concentrated and the resulting residue is stirred in warm (50° C.) THF (15 ml). This mixture is cooled (0° C.) and the solid collected by filtration and washed with cold THF. The solid is stirred in distilled water (200 ml), and the resulting solution made basic with K2CO3 and extracted with EtOAc (3×100 ml). The organic extracts are combined and dried over sodium sulfate, and then concentrated to give the title compound. MS (ESI) 180 (M+H)+.

Workup

  1. concentrationAfter 2.5 hours the reaction mixture is concentrated
  2. temperatureThis mixture is cooled (0° C.)
  3. filtrationthe solid collected by filtration
  4. washwashed with cold THF
  5. stirringThe solid is stirred in distilled water (200 ml)
  6. extractionextracted with EtOAc (3×100 ml)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9ebd1dccd3c54bc8a9b8f8de18541d78
Source dataset
uspto-grants-2006_02
Patent number
US07005440B1

Reaction notes

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