Cesium carbonate → [2-(4-Chloro-phenyl)-benzoimidazol-1-yl]-cyclohexyl-acetic acid ethyl ester

HRID 417080Notes

Reaction equation

HRID 417080 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:23]([O:25][C:26](=[O:35])[CH:27](Br)[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[CH3:24]>CN(C)C=O>[CH2:23]([O:25][C:26](=[O:35])[CH:27]([N:12]1[C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[N:9]=[C:8]1[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[CH3:24]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 7594172-(4-Chlorophenyl)benzimidazoleHCID 2762757Ethyl 2-bromo-2-cyclohexylacetate

Product 1

HCID 66619211[2-(4-Chloro-phenyl)-benzoimidazol-1-yl]-cyclohexyl-acetic acid ethyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To the solution of 1.0 g (4.4 mmol) 2-(4-chlorophenyl)benzimidazole (commercially available) in 10 mL N,N-dimethylformamide, 4.6 g (14.0 mmol) cesium carbonate and 3.3 g (13.1 mmol) bromo-cyclohexyl-acetic acid ethyl ester (commercially available) were added and the brown suspension was stirred for 22 h at 100° C. After cooling to room temperature the reaction was poured on water and extracted three times with ethyl acetate. The organic phases were washed with water and brine, dried over magnesium sulfate and filtered. To the filtrate silica gel was added and the solvent evaporated. The adsorbed crude product was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate 100:0 to 50:50) to give the desired compound as a colorless solid (58%). MS (Turbo Spray): m/z=397.2 [M+H].

Workup

  1. temperatureAfter cooling to room temperature the reaction
  2. additionwas poured on water
  3. extractionextracted three times with ethyl acetate
  4. washThe organic phases were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. additionTo the filtrate silica gel was added
  8. customthe solvent evaporated
  9. customThe adsorbed crude product was purified by silica gel chromatography
  10. washeluting with a gradient of n-heptane:ethyl acetate 100:0 to 50:50)

Sources & evidence

ORD record
ord-37e0e57d74d94cec8898d6758bc49860
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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