Ethyl 2-chloroacetoacetate → Ethyl 2-(4-methoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate

HRID 1708947Notes

Reaction equation

HRID 1708947 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[S:8])=[CH:5][CH:4]=1.Cl[CH:13]([C:19]([CH3:21])=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15]>C(O)C>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]2[S:8][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:19]([CH3:21])[N:9]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 7368274-Methoxybenzenecarbothioamide

Product 1

HCID 7540952Ethyl 2-(4-methoxyphenyl)-4-methyl-1,3-thiazole-5-carboxylateYield 76.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of p-methoxythiobenzamide (3 g, 17.95 mmol) dissolved in dry ethanol (180 ml) was added ethyl 2-chloroacetoacetate (1.28 ml, 8.98 mmol), and the mixture was heated under reflux for 1.5 hours. After the reaction was completed, the solvent was distilled off from the reaction mixture. Then the residue was treated with water, made weak alkali (pH=8) with saturated aqueous sodium carbonates, and extracted with ethyl acetate. The organic phase was washed with saturated saline and dried over anhydrous sodium sulfate. After removing the solvent by distillation, the residue was dissolved in chloroform (insoluble solids being filtered off) and applied on silica gel column (developing solvent:n-hexane:ethyl acetate=85:15). After discarding the first fraction (impurities), the second colorless fraction was pooled and concentrated to give 1.9 g of ethyl 2-(4-methoxyphenyl)-4-methyl-5-thiazolecarboxylate as white crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 1.5 hours
  3. distillationthe solvent was distilled off from the reaction mixture
  4. additionThen the residue was treated with water
  5. extractionextracted with ethyl acetate
  6. washThe organic phase was washed with saturated saline
  7. dry with materialdried over anhydrous sodium sulfate
  8. customAfter removing the solvent
  9. distillationby distillation
  10. dissolutionthe residue was dissolved in chloroform (insoluble solids being filtered off)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-7b76aed4ba2a4ddc92da432587be5eb7
Source dataset
uspto-grants-1990_08
Patent number
US04946855

Reaction notes

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