Monoethyl malonate → (R)N-[1-(4-Bromo-phenyl)-ethyl]-malonamic Acid Ethyl Ester

HRID 858576

Reaction equation

HRID 858576 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH2:10])[CH3:9])=[CH:4][CH:3]=1.[C:11]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:12][C:13](O)=[O:14].C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[CH2:18]([O:17][C:11](=[O:16])[CH2:12][C:13]([NH:10][C@@H:8]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)[CH3:9])=[O:14])[CH3:19]

Participants

5

Reactant 3

HCID 70615Monoethyl malonateHCID 757711-HydroxybenzotriazoleHCID 853000(R)-4-bromo-alpha-methylbenzylamine

Product 1

HCID 58762223(R)N-[1-(4-Bromo-phenyl)-ethyl]-malonamic Acid Ethyl EsterYield 71.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a magnetically stirred solution of (R)-(+)-1-(4-bromophenyl)ethylamine (0.51 g, 2.55 mmol) in anhydrous CH2Cl2 under argon and cooled to 0° C., were added ethyl hydrogen malonate (0.4 g, 3.06 mmol) EDC.HCl (0.58 g, 3.06 mmol) and HOBt (0.41 g, 3.06 mmol). The resulting solution was stirred at 25° C. overnight. CH2Cl2 was evaporate and residue partitioned between EtOAC and 1 N HCl. The organic layer was washed with H2O, brine and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (40% EtOAc in hexanes) to provide the desired product (0.57 g, 71%) as a white solid.

Workup

  1. customCH2Cl2 was evaporate
  2. customresidue partitioned between EtOAC and 1 N HCl
  3. washThe organic layer was washed with H2O, brine
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by flash column chromatography (40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b69fd6196b72414d81b4d2877f6e7555
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Linked notes

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