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

HRID 642318Notes

Reaction equation

HRID 642318 reaction equation
[C:1]([NH2:9])(=[S:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH2:10]([O:12][C:13](=[O:19])[CH:14](Cl)[C:15](=O)[CH3:16])[CH3:11]>C(O)C>[CH2:10]([O:12][C:13]([C:14]1[S:8][C:1]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[N:9][C:15]=1[CH3:16])=[O:19])[CH3:11]

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 737155Thionicotinamide

Product 1

HCID 619088Ethyl 4-methyl-2-(pyridin-3-yl)-1,3-thiazole-5-carboxylateYield 70.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of thionicotinamide (10 g, 0.07 mol) and 2-chloro-3-oxo-butyric acid ethyl ester (10 mL, 0.07 mol) in ethanol (100 mL) was heated at refluxed for 20 h before it was cooled to room temperature and concentrated in vacuo. It was partitioned between ethyl acetate and saturated sodium bicarbonate, the organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and hexanes to give the title compound as a yellow oil (12.2 g): MS: (+) m/z 249.0 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat refluxed for 20 h before it
  3. concentrationconcentrated in vacuo
  4. customIt was partitioned between ethyl acetate and saturated sodium bicarbonate
  5. washthe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-2d61ae193ea34b16a3c6ac78bb520765
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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