Ethyl bromoacetate → Ethyl 3-amino-3-[1-(4-chlorophenyl)cyclobutyl]acrylate

HRID 1650957Notes

Reaction equation

HRID 1650957 reaction equation
[CH2:1]([O:3][C:4](=[O:7])[CH2:5]Br)[CH3:2].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([C:19]#[N:20])[CH2:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.[Zn]>[NH2:20][C:19]([C:15]1([C:12]2[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=2)[CH2:16][CH2:17][CH2:18]1)=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[O:7]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetate2×HCID 11430Potassium CarbonateHCID 986211-(4-Chlorophenyl)cyclobutanecarbonitrile

Product 1

HCID 67945594Ethyl 3-amino-3-[1-(4-chlorophenyl)cyclobutyl]acrylate

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of zinc dust (25.5 g) (which had been activated by treatment with excess 3N hydrochloric acid followed by washing with water, ethanol and ether and drying) in dry tetrahydrofuran (250 ml) was stirred and heated under reflux while ethylbromoacetate (5 ml) was added dropwise. Stirring was continued for 15 minutes and 1-(4-chlorophenyl)cyclobutanecarbonitrile (15 g) was added. The mixture was heated under reflux and ethyl bromoacetate (60 g) was added over a period of 1 hour and the heating continued for a further 15 minutes. The mixture was then cooled and tetrahydrofuran (700 ml) and 25% aqueous potassium carbonate solution (300 ml) were added and the mixture was stirred for 15 minutes. The aqueous phase of the reaction mixture was separated, extracted with ether and the extracts combined with the organic phase of the reaction mixture, washed with brine and dried. Removal of the solvents gave an oil which was extracted with petroleum ether (b.p. 40°-60° C.). Removal of the solvent by evaporation gave ethyl 3-amino-3-[1-(4-chlorophenyl)cyclobutyl]acrylate.

Workup

  1. temperatureheated
  2. additionwas added dropwise
  3. stirringStirring
  4. temperatureThe mixture was heated
  5. temperatureunder reflux
  6. waitthe heating continued for a further 15 minutes
  7. temperatureThe mixture was then cooled
  8. stirringthe mixture was stirred for 15 minutes
  9. customThe aqueous phase of the reaction mixture was separated
  10. extractionextracted with ether
  11. washwashed with brine
  12. customdried
  13. customRemoval of the solvents
  14. customgave an oil which
  15. extractionwas extracted with petroleum ether (b.p. 40°-60° C.)
  16. customRemoval of the solvent
  17. customby evaporation

Sources & evidence

ORD record
ord-9daf99d50a9a4165ada0ada971e3f0e7
Source dataset
uspto-grants-1990_05
Patent number
US04925879

Reaction notes

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