Acetamidomalonic acid diethyl ester → Diethyl acetamido[(pyridin-4-yl)methyl]propanedioate

HRID 1182041Notes

Reaction equation

HRID 1182041 reaction equation
COC(=O)C([CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)NC(=O)CN(S(C1C=CC(C)=CC=1)(=O)=O)C.[Na].[C:30]([NH:33][CH:34]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:35]([O:37][CH2:38][CH3:39])=[O:36])(=[O:32])[CH3:31].Cl.N1C=CC(CCl)=CC=1>CCO>[N:25]1[CH:26]=[CH:27][C:22]([CH2:21][C:34]([NH:33][C:30](=[O:32])[CH3:31])([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 14041Acetamidomalonic acid diethyl esterHCID 745704-(Chloromethyl)pyridinium chlorideHCID 5360545SodiumHCID 18464215HCID 18464215, compound

Product 1

HCID 13817909Diethyl acetamido[(pyridin-4-yl)methyl]propanedioate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

N-(Toluene-4-sulfonyl)sarcosyl-β-(pyrid-4-yl)-D,L-alanine methyl ester was employed in this reaction and was prepared as follows. Sodium metal (2 eq.) was dissolved in EtOH containing diethyl acetamidomalonate (1 eq.) and 4-picolylchloride hydrochloride (1 eq.). The mixture was heated to reflux for 6 hr, 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 aq NaHCO3 and extracted with EtOAc. The solvent was removed and the residue purified by silica gel flash chromatography (95:5 CH2Cl2/MeOH) to give diethyl 2-(4-pyridylmethyl)-2-acetamidomalonate.

Workup

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

Sources & evidence

ORD record
ord-c6abbbed5d814d3f94bb564589c81bd1
Source dataset
uspto-grants-2007_10
Patent number
US07288526B2

Reaction notes

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