Acetamidomalonic acid diethyl ester → propanedioic acid, (acetylamino)[(4-cyanophenyl)methyl]-, diethyl ester

HRID 262235Notes

Reaction equation

HRID 262235 reaction equation
CC(C)([O-])C.[K+].[C:7]([NH:10][CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])(=[O:9])[CH3:8].[C:22]([C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1)#[N:23]>CN(C)C=O.CC(C)([O-])C.[K+]>[CH2:15]([O:14][C:12](=[O:13])[C:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])([CH2:28][C:27]1[CH:30]=[CH:31][C:24]([C:22]#[N:23])=[CH:25][CH:26]=1)[NH:10][C:7](=[O:9])[CH3:8])[CH3:16]

Participants

6

Reactant 3

HCID 14041Acetamidomalonic acid diethyl ester2×HCID 869964-(Bromomethyl)benzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 640014propanedioic acid, (acetylamino)[(4-cyanophenyl)methyl]-, diethyl esterYield 61%

Reagents, catalysts & solvents 2

HCID 23665647Potassium tert-butoxideCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To 50 ml of dimethylformamide is added 5.7 g (51 mmoles) of potassium tert-butoxide and 11.1 g (51 mmoles) of diethyl acetamidomalonate and the resulting mixture stirred at 25° for 15 minutes. The solution is then cooled to 10° and a solution of 10.0 g (51 mmoles) of 4-cyanobenzyl bromide, Case, J. Am. Chem. Soc., 47, 1143, (1925) in 40 ml of dimethylformamide is added dropwise over 20 minutes. The mixture is then stirred at 25° for 1 hour after which a further 0.285 g (2.5 mmoles) of potassium tert-butoxide and 0.55 (2.5 mmoles) of diethyl acetamidomalonate are added and stirring continued for 1 hour at 25°. The reaction mixture is then poured into 300 ml of ice water, causing the product to precipitate. Filtration, washing with water and drying yields 10.3 g (31 mmoles, 61%) of N-acetyl-4-cyano-α-(ethoxycarbonyl)phenylalanine ethyl ester, m.p. 160°-163°.

Workup

  1. temperatureThe solution is then cooled to 10°
  2. additionare added
  3. stirringstirring
  4. waitcontinued for 1 hour at 25°
  5. customto precipitate
  6. filtrationFiltration
  7. washwashing with water
  8. customdrying

Sources & evidence

ORD record
ord-5c7e3e4bd15c4e76bebc2657b5e4738b
Source dataset
uspto-grants-1979_05
Patent number
US04153715

Reaction notes

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