Sulfuric Acid → Methyl 1-benzyl-2,4-dioxo-3-piperidinecarboxylate

HRID 1257620Notes

Reaction equation

HRID 1257620 reaction equation
[CH2:1]([O:3][C:4](=[O:23])[CH2:5][C:6]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:9][CH2:10][C:11]([O:13]CC)=O)=[O:7])C.COC(=O)CC(N(CC1C=CC=CC=1)CCC(OCC)=O)=O.C[O-].[Na+].S(=O)(=O)(O)O>C1(C)C=CC=CC=1>[CH3:1][O:3][C:4]([CH:5]1[C:11](=[O:13])[CH2:10][CH2:9][N:8]([CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:6]1=[O:7])=[O:23]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 4303884Diethyl beta-oxobenzyliminodipropionateHCID 10942334Sodium MethoxideHCID 67324774N-benzyl-N-(2-ethoxycarbonyl-ethyl)-malonamic acid methyl ester

Product 1

HCID 22495601Methyl 1-benzyl-2,4-dioxo-3-piperidinecarboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The generated mixture of N-benzyl-N-(2-ethoxycarbonyl-ethyl)-malonamic acid ethyl ester and N-benzyl-N-(2-ethoxycarbonyl-ethyl)-malonamic acid methyl ester was treated with sodium methoxide (2.97 mL, 13.0 mmol, 25% solution) in toluene at reflux for 18 hours. The cooled reaction mixture was acidified with 10% sulfuric acid and concentrated under vacuum. The resulting residue was dissolved in DCM and washed with water and brine, then dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (gradient: 0 to 2% methanol in DCM) to afford 2.09 g (68%) of 1-benzyl-2,4-dioxo-piperidine-3-carboxylic acid methyl ester. 1H NMR (400 MHz, CDCl3) δ: 7.29 (m, 5H), 4.70 (s, 1H), 4.64 (s, 2H), 3.93 (s, 3H), 3.34 (t, 2H), 2.59 (t, 2H).

Workup

  1. temperatureat reflux for 18 hours
  2. customThe cooled reaction mixture
  3. concentrationconcentrated under vacuum
  4. dissolutionThe resulting residue was dissolved in DCM
  5. washwashed with water and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe resulting residue was purified by column chromatography on silica gel (gradient: 0 to 2% methanol in DCM)

Sources & evidence

ORD record
ord-7f0378b0346541eebbb4dcbcd263566c
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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