Diethyl Malonate → Diethyl (pyrimidin-2-yl)propanedioate

HRID 1907675Notes

Reaction equation

HRID 1907675 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:15]1[N:20]=[CH:19][CH:18]=[CH:17][N:16]=1>CN(C)C=O>[N:16]1[CH:17]=[CH:18][CH:19]=[N:20][C:15]=1[CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 744042-Chloropyrimidine

Product 1

HCID 2303274Diethyl (pyrimidin-2-yl)propanedioateYield 42.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4.80 g of sodium hydride (55% oil dispersion) was suspended in 50 ml of N,N-dimethylformamide. Into this, 17.60 g of diethyl malonate was added dropwise over a period of about 0.5 hours at room temperature under a nitrogen atmosphere. The mixture was stirred further for 0.5 hours at the same temperature, then, to the mixture was added 5.73 g of 2-chloropyrimidine. The mixture was stirred for 3 hours at 100° C. The reaction mixture was allowed to cool to room temperature. To the reaction mixture was added ice water, and extracted with ethyl acetate. The organic layer was washed with saturated brine three times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. 18.84 g of the resultant residue was subjected to silica gel column chromatography, to obtain 5.09 g of diethyl (2-pyrimidinyl)malonate.

Workup

  1. stirringThe mixture was stirred for 3 hours at 100° C
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine three times
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d794b33f11744ecb90857b66e6a5c6fb
Source dataset
uspto-grants-2013_12
Patent number
US08598176B2

Reaction notes

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