N-Fluorobenzenesulfonimide → 5-fluoro-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazole

HRID 1661911Notes

Reaction equation

HRID 1661911 reaction equation
Br[C:2]1[CH:23]=[C:22]([O:24][CH3:25])[C:5]2[N:6]([CH2:18][CH2:19][O:20][CH3:21])[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=3)=[N:8][C:4]=2[CH:3]=1.[Li]CCCC.[F:31]N(S(C1C=CC=CC=1)(=O)=O)S(C1C=CC=CC=1)(=O)=O>C1COCC1>[F:31][C:2]1[CH:23]=[C:22]([O:24][CH3:25])[C:5]2[N:6]([CH2:18][CH2:19][O:20][CH3:21])[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=3)=[N:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 588007N-FluorobenzenesulfonimideHCID 113841195-Bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazoleHCID 178418339Butyllithium

Product 1

HCID 577720685-fluoro-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazoleYield 11.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 400 mg (0.98 mmol) 5-bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazole in 3 ml dry THF, n-BuLi (0.740 ml, 1.18 mmol) is added slowly at −78° C. After stirring for 45 min. at −78° C. N-fluoro-bis(phenylsulfonyl)amine (568.7 mg, 1.77 mmol) is added. Stirring at −78° C. is continued for another hour and then the reaction mixture is warmed to room temperature. After that the reaction mixture is poured on water and extracted (3×) with ethyl acetate. The combined organic layers are washed with water (3×) and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel (hexane:EtOAc=2:1−>1:1) to afford 40 mg of the title compound as a colorless oil.

Workup

  1. stirringStirring at −78° C.
  2. waitis continued for another hour
  3. temperaturethe reaction mixture is warmed to room temperature
  4. additionAfter that the reaction mixture is poured on water
  5. extractionextracted (3×) with ethyl acetate
  6. washThe combined organic layers are washed with water (3×) and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by flash-chromatography on silica gel (hexane:EtOAc=2:1−>1:1)

Sources & evidence

ORD record
ord-37aa9c598664437da4c53513c81e6996
Source dataset
uspto-grants-2011_10
Patent number
US08030497B2

Reaction notes

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