Acetamidomalonic acid diethyl ester → Diethyl 5-isoxazolylmethylacetamidomalonate

HRID 1768585Notes

Reaction equation

HRID 1768585 reaction equation
[H-].[Na+].[C:3]([NH:6][CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4].Br[CH2:19][C:20]1[O:24][N:23]=[CH:22][CH:21]=1>CN(C)C=O>[O:24]1[C:20]([CH2:19][CH2:4][C:3]([NH:6][CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:5])=[CH:21][CH:22]=[N:23]1

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 100349035-(Bromomethyl)-1,2-oxazole

Product 1

HCID 57027705Diethyl 5-isoxazolylmethylacetamidomalonateYield 33,478.898%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3.1 g (70.7 mmole) of sodium hydride (as a 55% w/w dispersion in mineral oil) were added to a solution of 14.0 g (6,43 mmole) of diethyl acetamidomalonate dissolved in 150 ml of dimethylformamide, whilst ice-cooling, and the mixture was stirred for 1 hour. At the end of this time, 23.9 g (0.148 mmole) of 5-bromomethylisoxazole were added to the reaction mixture, which was then stirred at room temperature for 4.5 hours, The reaction mixture was then concentrated by evaporation under reduced pressure, and the residue was mixed with water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, after which it was concentrated by evaporation under reduced pressure. The residue was purified by silica gel column chromatography (eluent: a 1: 2 by volume mixture of ethyl acetate and hexane), to afford 14.78 g (77.1%) of the title compound, melting at 75°-76° C.

Workup

  1. temperaturecooling
  2. stirringwas then stirred at room temperature for 4.5 hours
  3. concentrationThe reaction mixture was then concentrated by evaporation under reduced pressure
  4. additionthe residue was mixed with water
  5. extractionextracted with ethyl acetate
  6. washThe extract was washed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationafter which it was concentrated by evaporation under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (eluent
  10. additiona 1: 2 by volume mixture of ethyl acetate and hexane),

Sources & evidence

ORD record
ord-e06aa6fe06454cd38c0172f0d78d5552
Source dataset
uspto-grants-1995_01
Patent number
US05378690

Reaction notes

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