p-Toluenesulfonic acid → 8-chloro-3-(4-chlorobenzyl)-5-hydroxy-2-methyl-1H-quinolin-4-one

HRID 2266418Notes

Reaction equation

HRID 2266418 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[Cl:8].C([O:12][C:13](=O)[CH:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)[C:15](=O)[CH3:16])C.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([OH:9])=[C:3]2[C:2]=1[NH:1][C:15]([CH3:16])=[C:14]([CH2:18][C:19]1[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=1)[C:13]2=[O:12]

Participants

4

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 2757404Ethyl 2-(4-chlorobenzyl)acetoacetateHCID 50700783-Amino-4-chlorophenol

Product 1

HCID 687826838-chloro-3-(4-chlorobenzyl)-5-hydroxy-2-methyl-1H-quinolin-4-one

Conditions

Temperature
160 °C

Procedure

A mixture of 3-amino-4-chlorophenol (2.5 g), 2-(4-chlorobenzyl)-3-oxobutyric acid ethyl ester (4.7 g) and toluene-4-sulfonic acid (0.3 g) was heated at 160° C. under nitrogen for 10 hours. The mixture was cooled to room temperature and the residue triturated with methanol and then crystallised from butan-1-ol to afford a beige powder. Purification by column chromatography on silica gel, eluting with a mixture of ethyl acetate and dichloromethane (0:1 to 1:0 by volume) gave title compound as a yellow solid, 0.77 g.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customthe residue triturated with methanol
  3. customcrystallised from butan-1-ol
  4. customto afford a beige powder
  5. customPurification by column chromatography on silica gel
  6. washeluting with a mixture of ethyl acetate and dichloromethane (0:1 to 1:0 by volume)

Sources & evidence

ORD record
ord-d097853a9901410291bfcb241f6ff002
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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