Acetamidomalonic acid diethyl ester → HCID 53945105, compound

HRID 1197508Notes

Reaction equation

HRID 1197508 reaction equation
[Na].[O-]CC.[Na+].[C:6]([NH:9][CH:10]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])(=[O:8])[CH3:7].Cl[CH2:22][C:23]1[N:24]=[CH:25][S:26][CH:27]=1>C(O)C.C(OCC)(=O)C.[I-].[K+].CN(C)C=O>[S:26]1[CH:27]=[C:23]([CH2:22][CH2:7][C:6]([NH:9][CH:10]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:8])[N:24]=[CH:25]1

Participants

9

Reactant 4

HCID 14041Acetamidomalonic acid diethyl esterHCID 2723922Sodium ethoxideHCID 27632904-(Chloromethyl)-1,3-thiazoleHCID 5360545Sodium2×

Product 1

HCID 53945105HCID 53945105, compoundYield 98%

Reagents, catalysts & solvents 4

HCID 4875Potassium IodideCatalystHCID 702EthanolSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To an oven-dried 2 liter 3-neck round bottom flask equipped with a mechanical stirrer, relux condenser and nitrogen inlet containing 500 mL of absolute ethanol was added sodium (19.8 g, 0.86 mole). This mixture was allowed to reflux until complete dissolution of the sodium metal. The resultant solution of sodium ethoxide was cooled to approximately 40° C. and diethyl acetamidomalonate (186.1 g, 0.86 mole) was added. The resultant mixture was refluxed for 30 minutes, then cooled to about 50° C. and treated with potassium iodide (2.0 g) and dimethylformamide (2 ml). A freshly prepared solution of 4-chloromethylthiazole (0.89 mole) in 200 mL of absolute ethanol was added dropwise over a period of 20 minutes and the mixture was maintained at 50° C. for 24 hours. The mixture was then cooled in an ice bath, diluted with ethyl acetate and filtered through a pad of Celite. Concentration and drying gave 265 g of the desired product as light yellow crystals. m.p. 104°-106° C.

Workup

  1. customround bottom flask equipped with a mechanical stirrer, relux condenser and nitrogen inlet
  2. temperaturethe mixture was maintained at 50° C. for 24 hours
  3. temperatureThe mixture was then cooled in an ice bath
  4. filtrationfiltered through a pad of Celite
  5. concentrationConcentration
  6. customdrying

Sources & evidence

ORD record
ord-9f45ab66698644428bc756d3b1c1ec68
Source dataset
uspto-grants-1994_01
Patent number
US05275950

Reaction notes

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