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

HRID 1253100Notes

Reaction equation

HRID 1253100 reaction equation
[C:1]([NH:4][CH:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].[Na].Cl.Cl[CH2:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1>CCO>[C:1]([NH:4][C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])([CH2:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2]

Participants

5

Reactant 3

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

Product 1

HCID 13817914Diethyl acetamido[(pyridin-3-yl)methyl]propanedioateYield 34%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

48 g of diethyl acetamidomalonate are added to 11 g of a solution of sodium in 300 ml of EtOH, and then, while heating under reflux, 36 g of 3-chloromethylpyridine hydrochloride are added and the mixture is kept under reflux for 5 h. The EtOH is evaporated off, the residue is taken up with water, the mixture is extracted and the extract is dried, concentrated and chromatographed on silica. Elution with a CH2Cl2 /AcOEt mixture, 60/40 by volume, gives 23 g of the expected compound.

Workup

  1. temperaturewhile heating
  2. temperatureunder reflux
  3. temperatureunder reflux for 5 h
  4. customThe EtOH is evaporated off
  5. extractionthe mixture is extracted
  6. customthe extract is dried
  7. concentrationconcentrated
  8. customchromatographed on silica
  9. washElution with a CH2Cl2 /AcOEt mixture, 60/40 by volume

Sources & evidence

ORD record
ord-abbbbf67b6e74ba49625755b1845dc92
Source dataset
uspto-grants-1988_05
Patent number
US04746648

Reaction notes

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