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

HRID 1025664Notes

Reaction equation

HRID 1025664 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[Cl:19])=[NH:11])=[CH:5][CH:4]=1.Br[CH:21]([CH3:29])[C:22](=O)[C:23]([O:25][CH2:26][CH3:27])=[O:24].C([O-])(O)=O.[Na+]>CC(O)C>[Cl:19][C:13]1[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=1[C:10]1[N:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[C:21]([CH3:29])=[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:11]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 11117285Ethyl 3-bromo-2-oxobutanoateHCID 178492291HCID 178492291, compound

Product 1

HCID 11188916ethyl 2-(2,4-dichlorophenyl)-1-(4-methoxyphenyl)-5-methyl-1H-imidazole-4-carboxylateYield 42%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Part A: N-(4-methoxyphenyl)-2,4-dichlorobenzenecarboxamidine (15.0 gram, 50.8 mmol) is dissolved in 2-propanol and ethyl 3-bromo-2-oxobutanoate (23.5 g, 2 molar equivalents) and NaHCO3 (8.5 gram, 2 molar equivalents) 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) to give ethyl 2-(2,4-dichlorophenyl)-5-methyl-1-(4-methoxy-phenyl)-1H-imidazole-4-carboxylate (8.61 g, 42% yield) as a solid. 1H-NMR (200 MHz, CDCl3): δ 7.33 (d, J=8 Hz, 1H), 7.27 (d, J=2 Hz, 1H), 7.18 (dd, J=8 Hz, J=2 Hz, 1H), 7.03 (dt, J=8 Hz, J=2 Hz, 2H), 6.85 (dt, J=8 Hz, J=2 Hz, 2H), 4.42 (q, J=7 Hz, 2H), 3.80 (s, 3H), 2.43 (s, 3H), 1.43 (t, J=7 Hz, 3H).

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)

Sources & evidence

ORD record
ord-f6000307d38c4786beff2c67527371a2
Source dataset
uspto-grants-2014_05
Patent number
US08729101B2

Reaction notes

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