Water → 6-Chloro-4-(4-fluorophenyl)-2-methyl-3-quinolinecarboxylic acid, ethyl ester

HRID 34294Notes

Reaction equation

HRID 34294 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)=O.[C:18]([O:24][CH2:25][CH3:26])(=[O:23])[CH2:19][C:20]([CH3:22])=O.O>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Cl:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[N:1]=[C:20]([CH3:22])[C:19]([C:18]([O:24][CH2:25][CH3:26])=[O:23])=[C:9]2[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 962WaterHCID 8868Ethyl AcetoacetateHCID 109559554-Chloro-2-(4-fluorobenzoyl)aniline

Product 1

HCID 142293266-Chloro-4-(4-fluorophenyl)-2-methyl-3-quinolinecarboxylic acid, ethyl esterYield 73.9%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Procedure

To a solution of (2-amino-5-chlorophenyl)-(4-fluorophenyl)methanone (10.0 g) in 100 mL of toluene was added 8.3g (1.6 equivalents) of ethyl acetoacetate and 0.30 g of p-toluenesulfonic acid. The resulting mixture was heated to reflux with azeotropic removal of water. After one and one-half hours, the mixture was cooled to room temperature and concentrated under vacuum. The crude product was purified by flash chromatography over silica gel to give 10.18 g of 6-chloro-4-(4-fluorophenyl)-2-methyl-3-quinolinecarboxylic acid, ethyl ester as an off-white solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. concentrationconcentrated under vacuum
  3. customThe crude product was purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-3bbf653c96e04d58a6fabada210186c8
Source dataset
uspto-grants-1988_08
Patent number
US04761419

Reaction notes

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