N-(4-Chlorophenyl)acetamide → 2-[4-(4-Chloroanilino)-phenyl]propionic acid

HRID 1576580Notes

Reaction equation

HRID 1576580 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:13])[C:9]([O:11]C)=[O:10])=[CH:4][CH:3]=1.CC([NH:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1)=O.C(=O)([O-])[O-].[K+].[K+]>[Cu]>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:13])[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 10871N-(4-Chlorophenyl)acetamideHCID 11430Potassium CarbonateHCID 10589545Methyl 2-(4-iodophenyl)propanoate

Product 1

HCID 215114592-[4-(4-Chloroanilino)-phenyl]propionic acid

Reagents, catalysts & solvents 1

HCID 23978CopperCatalyst

Procedure

Methyl 2-(4-iodophenyl)propionate (2 g.), acet-p-chloroanilide (1.17 g.), potassium carbonate (0.62 g.) and copper powder (0.1 g.) were heated at 165°C. for 7.5 hours. The cooled solid was triturated with methylene chloride, filtered, and the filtrate evaporated to dryness. The residue was refluxed for 1.5 hours with ethanol (7 ml.) and 2.5N sodium hydroxide (14 ml.); ethanol was distilled in vacuo and the residue diluted with water, washed with ether and acidified with dilute hydrochloric acid. The resulting oil was isolated in ether and evaporated to dryness. The resulting gum was purified by preparative layer chromatography using 5% acetic acid/petroleum ether b.p. 62°-68°C. and eluting with ethyl acetate; recrystallization from benzene/petroleum ether b.p. 62°-68°C. and from petroleum ether b.p. 80°-100°C. gave 2-[4-(4-chloroanilino)-phenyl]propionic acid, m.p. 106-109°C.

Workup

  1. customThe cooled solid was triturated with methylene chloride
  2. filtrationfiltered
  3. customthe filtrate evaporated to dryness
  4. temperatureThe residue was refluxed for 1.5 hours with ethanol (7 ml.) and 2.5N sodium hydroxide (14 ml.)
  5. distillationethanol was distilled in vacuo
  6. additionthe residue diluted with water
  7. washwashed with ether
  8. customThe resulting oil was isolated in ether
  9. customevaporated to dryness
  10. customThe resulting gum was purified by preparative layer chromatography
  11. washeluting with ethyl acetate
  12. customrecrystallization from benzene/petroleum ether b.p. 62°-68°C.

Sources & evidence

ORD record
ord-1f49bad261de4cf89ce7a4d1bf627ad7
Source dataset
uspto-grants-1976_09
Patent number
US03981905

Reaction notes

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