Ethyl Acetate → Benzyl 3-amino-3-(2-ethoxy-2-oxoethyl)pyrrolidine-1-carboxylate

HRID 1192884Notes

Reaction equation

HRID 1192884 reaction equation
O=[C:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.C([O-])(=O)C.[NH4+:21].[C:22]([O:28][CH2:29][CH3:30])(=[O:27])[CH2:23]C([O-])=O.C(OCC)(=O)C>CCO>[NH2:21][C:2]1([CH2:23][C:22]([O:28][CH2:29][CH3:30])=[O:27])[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 517165Ammonium AcetateHCID 5612031-N-Cbz-3-pyrrolidinoneHCID 3595298Propanedioic acid, monoethyl ester

Product 1

HCID 66864898Benzyl 3-amino-3-(2-ethoxy-2-oxoethyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of benzyl 3-oxopyrrolidine-1-carboxylate (2.03 g, 10 mmol) and ammonium acetate (977 mg, 12.7 mmol) in EtOH (10 mL) was treated with ethyl malonate (1.07 mL, 9.09 mmol). The resulting solution was heated to reflux for 4 h and cooled to room temperature. Ethyl acetate (200 mL) was added and the solution was washed with saturated NaHCO3 (25 mL), brine (25 mL), dried over MgSO4 and concentrated to dryness. The mixture was filtered through a silica gel plug with ethyl acetate followed by methanol to elute the title compound as a yellow oil (600 mg, 19%). 1H NMR (400 MHz, CD3OD) δ 7.40-7.32 (m, 5H), 4.23 (q, 2H, J=7.4 Hz), 3.81-3.76 (m, 1H), 3.66-3.56 (m, 3H), 2.94 (s, 2H), 2.29-2.24 (m, 2H), 1.29 (t, 3H, J=7.4 Hz). MS ESI 307.1 [M+H]+, calcd for [C16H22N2O4+H]+ 307.16.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 4 h
  3. washthe solution was washed with saturated NaHCO3 (25 mL), brine (25 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness
  6. filtrationThe mixture was filtered through a silica gel plug with ethyl acetate
  7. washto elute the title compound as a yellow oil (600 mg, 19%)

Sources & evidence

ORD record
ord-aba1919af41c42f4a5e467f72afe4b3f
Source dataset
uspto-grants-2014_03
Patent number
US08680282B2

Reaction notes

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