2-Oxobutanoic Acid → 6-Fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

HRID 245210Notes

Reaction equation

HRID 245210 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[O:9][CH3:10].[F:11][C:12]([F:22])([F:21])[C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH:16]=O.O=[C:24]([CH2:28][CH3:29])[C:25]([OH:27])=[O:26]>C(O)C>[F:1][C:2]1[CH:8]=[C:7]2[C:5](=[CH:4][C:3]=1[O:9][CH3:10])[N:6]=[C:16]([C:15]1[CH:18]=[CH:19][CH:20]=[C:13]([C:12]([F:22])([F:21])[F:11])[CH:14]=1)[C:28]([CH3:29])=[C:24]2[C:25]([OH:27])=[O:26]

Participants

5

Reactant 3

HCID 582-Oxobutanoic AcidHCID 679903-(Trifluoromethyl)benzaldehydeHCID 27745334-Fluoro-3-methoxyaniline

Product 1

HCID 673840026-Fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 43.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-fluoro-3-(methyloxy)aniline (25.0 g, 177 mmol) in ethanol (300 mL) was added 3-(trifluoromethyl)benzaldehyde (30.8 g, 177 mmol) dropwise. The mixture was stirred at reflux for 1 h, and 2-oxobutanoic acid (18.08 g, 177 mmol) was added portionwise. The reaction mixture was stirred at reflux for an additional 3 h, cooled to room temperature, and stirred overnight. The solid precipitate was collected by filtration, washed with ethanol, and air dried to give 6-fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (29.1 g, 43% yield). 1H NMR (400 MHz, DMSO-d6) δ14.34 (br. s., 1H), 7.94-7.98 (m, 2H), 7.88 (d, J=7.78 Hz, 1H), 7.77 (t, J=7.65 Hz, 1H), 7.71 (d, J=8.53 Hz, 1H), 7.54 (d, J=12.05 Hz, 1H), 4.03 (s, 3H), 2.38 (s, 3H); MS (m/z) 380.1 (M+H+).

Workup

  1. temperatureat reflux for 1 h
  2. stirringThe reaction mixture was stirred
  3. temperatureat reflux for an additional 3 h
  4. stirringstirred overnight
  5. filtrationThe solid precipitate was collected by filtration
  6. washwashed with ethanol, and air
  7. customdried

Sources & evidence

ORD record
ord-404b431e31034dc692f305796c391924
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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