3-(Trifluoromethyl)aniline → 2-Methyl-7-(trifluoromethyl)quinoline

HRID 338858

Reaction equation

HRID 338858 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].[CH:12](=O)/[CH:13]=[CH:14]/[CH3:15].C(OCC)(=O)C>Cl.O>[CH3:15][C:14]1[CH:13]=[CH:12][C:7]2[C:5](=[CH:4][C:3]([C:2]([F:10])([F:11])[F:1])=[CH:9][CH:8]=2)[N:6]=1

Participants

6

Reactant 3

HCID 73753-(Trifluoromethyl)anilineHCID 8857Ethyl AcetateHCID 447466Crotonaldehyde

Product 1

HCID 224169042-Methyl-7-(trifluoromethyl)quinolineYield 28.9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent

Procedure

To a solution of 3-(trifluoromethyl)aniline (12.43 mL, 99.92 mmol) in 6 N HCl (50 mL) in water was added (E)-but-2-enal (18.77 mL, 229.8 mmol) dropwise at reflux. The reaction was stirred at reflux for 3 hours. After cooling to ambient temperature, ethyl acetate (200 mL) was added. The aqueous layer was separated, basified with ammonium hydroxide to about pH 9, and extracted with DCM (2×200 mL). The combined organic layers were dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (5:1 hexane/ethyl acetate) to give 2-methyl-7-(trifluoromethyl)quinoline (6.1 g, 28.9%) as a solid.

Workup

  1. temperatureat reflux
  2. temperatureat reflux for 3 hours
  3. customThe aqueous layer was separated
  4. extractionextracted with DCM (2×200 mL)
  5. dry with materialThe combined organic layers were dried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel (5:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f0ad4393e48c40d8b061304cc8e6b1e3
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Linked notes

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