Potassium Carbonate → 1-(4-Benzyloxyphenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid ethyl ester

HRID 1715092Notes

Reaction equation

HRID 1715092 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[NH:25])[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:32]([O:34][C:35](=[O:41])[C:36](=O)[CH:37](Br)[CH3:38])[CH3:33]>C1COCC1>[CH2:32]([O:34][C:35]([C:36]1[N:25]=[C:16]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])[N:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:14][CH:13]=2)[C:37]=1[CH3:38])=[O:41])[CH3:33]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 11117285Ethyl 3-bromo-2-oxobutanoateHCID 178512056HCID 178512056, compound

Product 1

HCID 594655051-(4-Benzyloxyphenyl)-2-(2,4-dichlorophenyl)-5-methyl-1H-imidazole-4-carboxylic acid ethyl esterYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To N-(4-benzyloxyphenyl)-2,4-dichlorobenzamidine, from Ex. 1, Step 1 (6.88 g, 18.5 mmol) dissolved in 50 ml THF was added potassium carbonate (2.56 g, 18.5 mmol) and the suspension was stirred for 10 minutes. Ethyl-3-bromo-2-oxobutanoate (4.65 g, 22.2 mmol) was dropwise added over 1 hour, and the mixture was stirred for 66 hours at room temperature. The solution was filtered and evaporated to dryness. The residue was dissolved in acetic acid and refluxed for 1 hour. The mixture was cooled to room temperature, 100 ml water added and the product extracted with EtOAc (2×200 ml). The combined organic phases were washed with saturated sodium hydrogen carbonate, dried (Na2SO4), filtered and concentrated. Flash chromatography (silica, hexane:EtOAc 70:30, 60:40) afforded 5.75 g (65%) of the title compound as a pale yellow solid.

Workup

  1. stirringthe mixture was stirred for 66 hours at room temperature
  2. filtrationThe solution was filtered
  3. customevaporated to dryness
  4. dissolutionThe residue was dissolved in acetic acid
  5. temperaturerefluxed for 1 hour
  6. addition100 ml water added
  7. extractionthe product extracted with EtOAc (2×200 ml)
  8. washThe combined organic phases were washed with saturated sodium hydrogen carbonate
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e851876f0f7e4358b02b484af569d363
Source dataset
uspto-grants-2010_09
Patent number
US07799804B2

Reaction notes

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