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

HRID 1370228Notes

Reaction equation

HRID 1370228 reaction equation
[C:1]([NH:4][CH:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].[C:16]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1)#[N:17].CC[O-].[Na+].O>CCO>[C:1]([NH:4][C:5]([CH2:22][C:21]1[CH:24]=[CH:25][C:18]([C:16]#[N:17])=[CH:19][CH:20]=1)([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 14041Acetamidomalonic acid diethyl esterHCID 869964-(Bromomethyl)benzonitrileHCID 2723922Sodium ethoxide

Product 1

HCID 640014propanedioic acid, (acetylamino)[(4-cyanophenyl)methyl]-, diethyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Diethyl 2-acetamidomalonate was treated with 4-cyanobenzyl bromide and NaOEt in EtOH, to give after dilution with H2O, and isolation of the resulting precipitate, diethyl 2-acetamido-2-(4-cyanobenzyl)malonate. This product was heated in HCl, and the mixture evaporated to give 4-carboxy-D,L-phenylalanine hydrochloride [D,L-Phe(4-CO2H)-OH.HCl]. This product was treated with MeOH and HCl gas to give after evaporation, D,L-Phe(4CO2Me)-OMeHCl. This product was treated with N-(toluene-4-sulfonyl)-L-Pro-OH, BOP, and NMM in DMF, to give after aqueous workup and flash chromatography, N-(toluene-4-sulfonyl)-L-Pro-D,L-Phe(4-CO2Me)-OMe. This product was treated with NaOH in dioxane and water, to give after acidification, extraction, drying with MgSO4, filtration and evaporation the title compound as a clear oil.

Sources & evidence

ORD record
ord-6d9b4215a10544058b9dce40e9c1f30d
Source dataset
uspto-grants-2003_06
Patent number
US06583139B1

Reaction notes

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