Ethyl 2-chloroacetoacetate → ethyl 4-methyl-2-[3-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate

HRID 1767925Notes

Reaction equation

HRID 1767925 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([NH2:8])=[S:7].Cl[CH:15]([C:21]([CH3:23])=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17]>C(O)C>[CH2:19]([O:18][C:16]([C:15]1[S:7][C:6]([C:5]2[CH:9]=[CH:10][CH:11]=[C:3]([C:2]([F:1])([F:12])[F:13])[CH:4]=2)=[N:8][C:21]=1[CH3:23])=[O:17])[CH3:20]

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 27778493-Trifluoromethylthiobenzamide

Product 1

HCID 2774390ethyl 4-methyl-2-[3-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3-trifluoromethyl-thiobenzamide (5 g, 23.2 mmol) and ethyl 2-chloro-acetoacetate (3.2 ml, 23.2 mmol) in ethanol (300 ml) was heated at reflux temperature for 14 hours. The solvent was removed under reduced pressure and the residue partitioned between ice water and ethyl acetate. The layers were separated and the aqueous phase extracted two times with ethyl acetate. The combined extracts were washed two times with ice water/brine 1/1 and dried over sodium sulfate. The solvent was removed under reduced pressure to give a yellow oil which was purified by column chromatography (silica gel, cyclohexane/dichloromethane) to yield 5.1 g (16.2 mmol, 70%) of the title compound as colorless crystals.

Workup

  1. temperatureat reflux temperature for 14 hours
  2. customThe solvent was removed under reduced pressure
  3. customthe residue partitioned between ice water and ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous phase extracted two times with ethyl acetate
  6. washThe combined extracts were washed two times with ice water/brine 1/1
  7. dry with materialdried over sodium sulfate
  8. customThe solvent was removed under reduced pressure
  9. customto give a yellow oil which
  10. customwas purified by column chromatography (silica gel, cyclohexane/dichloromethane)

Sources & evidence

ORD record
ord-8ae553958a114cc3a997022c19ee14c7
Source dataset
uspto-grants-2007_06
Patent number
US07235572B2

Reaction notes

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