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

HRID 1453023Notes

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

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 1N 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. 1H NMR (CDCl3): δ 1.29 (t, J=7.2 Hz, 3H), 1.48 (d, J=7.0 Hz, 3H), 3.31 (d, J=1.9 Hz, 2H), 4.2 (q, J=7.2 Hz, 2H), 5.06-5.14 (m, 1H), 7.20 (d, J=8.3 Hz, 2H), 7.45 (d, J=8.3 Hz, 2H), 7.48 (brs, 1H). ESIMS (MH+): 315

Workup

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

Sources & evidence

ORD record: ord-d8143e119e044966b7eed25c9557afcf
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07473790B2

Reaction notes

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