Phenol → 4-Bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-5-phenoxy methyl-1H-benzoimidazole

HRID 1661942Notes

Reaction equation

HRID 1661942 reaction equation
[C:1]1(O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Br:10][C:11]1[C:19]2[N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:22][CH:21]=3)[N:16]([CH2:29][CH2:30][O:31][CH3:32])[C:15]=2[C:14]([O:33][CH3:34])=[CH:13][C:12]=1[CH2:35][O:36]S(C)(=O)=O>CN(C=O)C>[Br:10][C:11]1[C:19]2[N:18]=[C:17]([C:20]3[CH:25]=[CH:24][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:22][CH:21]=3)[N:16]([CH2:29][CH2:30][O:31][CH3:32])[C:15]=2[C:14]([O:33][CH3:34])=[CH:13][C:12]=1[CH2:35][O:36][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 57771995methanesulfonic acid 4-bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazol-5-ylmethyl ester

Product 1

HCID 577720284-Bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-5-phenoxy methyl-1H-benzoimidazoleYield 93.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled solution (ice bath) of phenol (7.2 mg, 0.077 mmol) in 1 ml DMF, NaH (3.1 mg, 0.077 mmol, 60% in mineral oil) is added and the reaction is warmed to RT. Methanesulfonic acid 4-bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazol-5-ylmethyl ester (30 mg, 0.059 mmol) is added and the reaction mixture is heated to 60° C. for 1 h. After that the reaction mixture is extracted with sat. NaHCO3-solution and diethyl ether. The combined organic layers are washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel (hexane:EtOAc=1:1) to afford 28 mg of the title compound as pale yellow crystals.

Workup

  1. temperaturethe reaction mixture is heated to 60° C. for 1 h
  2. extractionAfter that the reaction mixture is extracted with sat. NaHCO3-solution and diethyl ether
  3. washThe combined organic layers are washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash-chromatography on silica gel (hexane:EtOAc=1:1)

Sources & evidence

ORD record
ord-d04c012b06904f56b5a682bf25c1bac6
Source dataset
uspto-grants-2011_10
Patent number
US08030497B2

Reaction notes

Loading…