Benzyl Bromide → 1-Benzyl-6-chloro-5-iodo-2-methanesulfonyl-1H-benzoimidazole

HRID 1960153Notes

Reaction equation

HRID 1960153 reaction equation
[Cl:1][C:2]1[C:3]([I:15])=[CH:4][C:5]2[N:9]=[C:8]([S:10]([CH3:13])(=[O:12])=[O:11])[NH:7][C:6]=2[CH:14]=1.[H-].[Na+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[CH2:18]([N:7]1[C:6]2[CH:14]=[C:2]([Cl:1])[C:3]([I:15])=[CH:4][C:5]=2[N:9]=[C:8]1[S:10]([CH3:13])(=[O:12])=[O:11])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 574814665-chloro-6-iodo-2-(methylsulfonyl)-1H-benzo[d]imidazole

Product 1

HCID 674461461-Benzyl-6-chloro-5-iodo-2-methanesulfonyl-1H-benzoimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-chloro-5-iodo-2-methanesulfonyl-1H-benzoimidazole (12.1 g, 34 mmol) in DMF (100 ml) at 0° C. was added NaH (60% dispersion in mineral oil, 1.5 g, 38 mmol). After 10 minutes, the mixture was warmed to rt and stirred for 45 minutes. Benzyl bromide (6.4 g, 38 mmol) was then slowly added and the reaction was stirred overnight at rt. The volatiles were then removed by rotary evaporation and the residue was partitioned between EtOAc and half-saturated ammonium chloride solution. The resulting emulsion was filtered through celite to obtain a cleaner partition. The EtOAc layer was washed with H2O, brine, and dried with MgSO4. After rotary evaporation, the oily residue was stirred in diethyl ether overnight. The mixture was filtered and the beige solid thus obtained was dried under vacuum at rt for 24 hours to yield the title compound. The filtrate was evaporated to an oil and purified by flash chromatography (SiO2, 220 g). A second crop of the title compound was eluted from the column with 40% EtOAc in hexane.

Workup

  1. stirringthe reaction was stirred overnight at rt
  2. customThe volatiles were then removed by rotary evaporation
  3. customthe residue was partitioned between EtOAc and half-saturated ammonium chloride solution
  4. filtrationThe resulting emulsion was filtered through celite
  5. customto obtain
  6. customa cleaner partition
  7. washThe EtOAc layer was washed with H2O, brine
  8. dry with materialdried with MgSO4
  9. customAfter rotary evaporation
  10. stirringthe oily residue was stirred in diethyl ether overnight
  11. filtrationThe mixture was filtered
  12. customthe beige solid thus obtained
  13. customwas dried under vacuum at rt for 24 hours

Sources & evidence

ORD record
ord-44e9625be9f44b559eeaaffc371014fa
Source dataset
uspto-grants-2013_04
Patent number
US08410284B2

Reaction notes

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