Acetamidomalonic acid diethyl ester → Diethyl acetamido[(pyridin-3-yl)methyl]propanedioate

HRID 636163Notes

Reaction equation

HRID 636163 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].Cl.[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24]Cl)[CH:19]=1>CCO>[N:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][C:6]([NH:5][C:2](=[O:4])[CH3:3])([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:19]=1

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 5360545Sodium

Product 1

HCID 13817914Diethyl acetamido[(pyridin-3-yl)methyl]propanedioateYield 30.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium metal (1.40 g, 61 mmol) was dissolved in EtOH (100 mL) and diethyl acetamidomalonate (6.62 g, 30.5 mmol) and 3-picolylchloride hydrochloride (5.00g, 30.5 mmol) were added. The mixture was heated to reflux for 6 hours, and then cooled and filtered to remove NaCl (washed with EtOH). The solvent was removed in vacuo and the mixture was taken up into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (3×100 mL). The solvent was removed and the residue purified by silica gel flash chromatography (95:5 CH2Cl2/MeOH) to give diethyl 2-(3-pyridylmethyl)-2-acetamidomalonate (2.84 g, 30%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 6 hours
  3. temperaturecooled
  4. filtrationfiltered
  5. customto remove NaCl (washed with EtOH)
  6. customThe solvent was removed in vacuo
  7. extractionextracted with EtOAc (3×100 mL)
  8. customThe solvent was removed
  9. customthe residue purified by silica gel flash chromatography (95:5 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-90a60d8d53124985a6ea238ddcd453a3
Source dataset
uspto-grants-2001_02
Patent number
US06191166B1

Reaction notes

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