Acetamidomalonic acid diethyl ester → Diethyl 1-Acetyl-5-hydroxy-3-ethylpyrrolidine-2,2-dicarboxylate

HRID 2258603Notes

Reaction equation

HRID 2258603 reaction equation
[Na].[C:2]([NH:5][CH:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:4])[CH3:3].[CH:17](=[O:22])/[CH:18]=[CH:19]/[CH2:20][CH3:21]>CCO>[C:2]([N:5]1[CH:17]([OH:22])[CH2:18][CH:19]([CH2:20][CH3:21])[C:6]1([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:4])[CH3:3]

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 5360545SodiumHCID 5364752(E)-2-Pentenal

Product 1

HCID 11289610Diethyl 1-Acetyl-5-hydroxy-3-ethylpyrrolidine-2,2-dicarboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

Sodium (4.02 g, 0.175 mol) was dissolved in a stirred solution of diethyl acetamidomalonate (235.4 g, 1.19 mol) in abs EtOH (1.4 L) at ambient temperature under argon. The reaction mixture was cooled to 0° C., and trans-2-pentenal (100 g, 1.08 mol) was added dropwise maintaining the reaction temperature at <5° C. After the addition, the reaction was allowed to warm to room temperature, stirred for 4 h, then quenched with acetic acid (28 mL). The solution was concentrated in vacuo, and the residue dissolved in EtOAc (1.5 L), washed with 10% NaHCO3 solution (2×300 mL), brine, and dried (MgSO4). The solution was filtered and concentrated to 700 mL, then heated to reflux and treated with hexane (1 L). On cooling, the title compound precipitated and was collected to give 287 g. 1H NMR (CD3OD) δ 5.65 (d, 1H, J=5 Hz), 4.1-4.25 (m, 4H), 2.7-2.8 (m, 1H), 2.21 (s, 3H), 2.10 (dd, 1H, J=6, 13, Hz), 1.86-1.97 (m, 2H), 1.27 (t, 3H, J=7 Hz), 1.23 (t, 3H, J=7 Hz), 1.1-1.25 (m, 1H), 0.97 (t, 3H, J=7 Hz).

Workup

  1. temperaturemaintaining the reaction temperature at <5° C
  2. additionAfter the addition
  3. temperatureto warm to room temperature
  4. customquenched with acetic acid (28 mL)
  5. concentrationThe solution was concentrated in vacuo
  6. dissolutionthe residue dissolved in EtOAc (1.5 L)
  7. washwashed with 10% NaHCO3 solution (2×300 mL), brine
  8. dry with materialdried (MgSO4)
  9. filtrationThe solution was filtered
  10. concentrationconcentrated to 700 mL
  11. temperatureheated
  12. temperatureto reflux
  13. additiontreated with hexane (1 L)
  14. temperatureOn cooling
  15. customthe title compound precipitated
  16. customwas collected
  17. customto give 287 g

Sources & evidence

ORD record
ord-a4f0aeb079c44b759d5f3a936d3f95cb
Source dataset
uspto-grants-1997_08
Patent number
US05661161

Reaction notes

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