Sodium Bicarbonate → ethyl 2-(2,4-dichlorophenyl)-5-methyl-1-(4-(trifluoromethyl)phenyl)-1H-imidazole-4-carboxylate

HRID 1025663Notes

Reaction equation

HRID 1025663 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1)=[NH:10].Br[CH:23]([CH3:31])[C:24](=O)[C:25]([O:27][CH2:28][CH3:29])=[O:26].C([O-])(O)=O.[Na+]>CC(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:11]([C:12]2[CH:13]=[CH:14][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:16][CH:17]=2)[C:23]([CH3:31])=[C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:10]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 11117285Ethyl 3-bromo-2-oxobutanoateHCID 178512013HCID 178512013, compound

Product 1

HCID 11201587ethyl 2-(2,4-dichlorophenyl)-5-methyl-1-(4-(trifluoromethyl)phenyl)-1H-imidazole-4-carboxylateYield 52.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Part C: 2,4-Dichloro-N-(4-(trifluoromethyl)phenyl)benzenecarboxamidine (15.0 g, 0.0450 mol) is dissolved in 2-propanol and ethyl 3-bromo-2-oxobutanoate (20.8 g, 2 molar equivalent) and NaHCO3 are successively added. The resulting mixture is heated at reflux temperature for 40 hours and allowed to attain room temperature. The 2-propanol is removed in vacuo, ethyl acetate is added to the residue and the resulting organic layer is washed with NaHCO3 (5% aqueous solution). The ethylacetate layer is collected, dried over Na2SO4, filtered and concentrated in vacuo. The resulting oil is purified by column chromatography (diethyl ether/petroleum ether=1/3 (v/v), silicagel) and further purified by crystallisation from cyclohexane to give ethyl 2-(2,4-dichlorophenyl)-5-methyl-1-(4-(trifluoromethyl)phenyl)-1H-imidazole-4-carboxylate (10.45 g, 52% yield) as a yellow solid. Melting point: 160-162° C.

Workup

  1. temperatureThe resulting mixture is heated
  2. temperatureat reflux temperature for 40 hours
  3. customto attain room temperature
  4. customThe 2-propanol is removed in vacuo, ethyl acetate
  5. additionis added to the residue
  6. washthe resulting organic layer is washed with NaHCO3 (5% aqueous solution)
  7. customThe ethylacetate layer is collected
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting oil is purified by column chromatography (diethyl ether/petroleum ether=1/3 (v/v), silicagel)
  12. customfurther purified by crystallisation from cyclohexane

Sources & evidence

ORD record
ord-2b54385312f94ea38597c2d135ac7ef2
Source dataset
uspto-grants-2014_05
Patent number
US08729101B2

Reaction notes

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