Aniline → Methyl 5-anilino-5-(4-chlorophenyl)pentanoate

HRID 1904612Notes

Reaction equation

HRID 1904612 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([CH2:8][CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=O)=[CH:4][CH:3]=1.[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[NH:17]([CH:6]([C:5]1[CH:15]=[CH:16][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH2:8][CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 2

HCID 6115AnilineHCID 10966649Methyl 5-(4-chlorophenyl)-5-oxovalerate

Product 1

HCID 14576811Methyl 5-anilino-5-(4-chlorophenyl)pentanoateYield 94.5%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
-20 °C

Procedure

(1)-a) To 19.0 g of methyl 4-(4-chlorobenzoyl)butyrate were added 14.5 g of aniline, 0.6 g of p-toluenesulfonic acid monohydrate and 200 ml of toluene, and the mixture was refluxed with dehydration for 22.5 hours. After removal of the solvent under reduced pressure, 100 ml of methanol and 2.5 g of sodium hydrogencarbonate were added, and the mixture was cooled to -20° C. Subsequently, 6.0 g of sodium borohydride was added portionwise over 1 hour, and the mixture was stirred at -30° to -20° C. for 1 hour and at -20° to -5° C. for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The ethyl acetate extracts were washed with diluted hydrochloric acid, and aqueous sodium hydrogencarbonate solution and water, and dried, followed by evaporation of the solvent to give 23.7 g of methyl 5-anilino-5-(4-chlorophenyl)pentanoate as a pale brown oily product. Subsequently, to said oily product were added 75 ml of methanol and 100 ml of an aqueous 10% sodium hydroxide solution, and the mixture was heated under reflux for 1 hour. After removal of the solvent, the residue was diluted with 50 ml of water and then ashed with ether. The aqueous layer was adjusted to pH 6 to 7 with hydrochloric acid, extracted with ethyl acetate. The ethyl acetate extract was washed with diluted hydrochloric acid and a saturated aqueous sodium chloride solution, dried, and treated with activated charcoal. After removal of charcoal and the solvent, the residue was recrystallized from isopropyl ether to give 17.8 g of 5-anilino-5-(4-chlorophenyl)pentanoic acid as colorless prisms.

Workup

  1. temperaturethe mixture was refluxed with dehydration for 22.5 hours
  2. customAfter removal of the solvent under reduced pressure, 100 ml of methanol and 2.5 g of sodium hydrogencarbonate
  3. additionwere added
  4. additionSubsequently, 6.0 g of sodium borohydride was added portionwise over 1 hour
  5. additionThe reaction mixture was diluted with water
  6. extractionextracted with ethyl acetate
  7. washThe ethyl acetate extracts were washed with diluted hydrochloric acid, and aqueous sodium hydrogencarbonate solution and water
  8. customdried
  9. customfollowed by evaporation of the solvent

Sources & evidence

ORD record
ord-3c403972a08f4e8d858a6c532f015339
Source dataset
uspto-grants-1989_06
Patent number
US04839360

Reaction notes

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