Tetrahydrofuran → 7-chloro-2-(2-ethylsulfanylphenyl)-1-methyl-5-trifluoromethyl-1H-benzimidazole

HRID 533619Notes

Reaction equation

HRID 533619 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([NH2:12])[C:3]=1[NH:13][CH3:14].C1COCC1.Cl.[CH2:21]([S:23][C:24]1[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26](O)=O)[CH3:22].C(=O)([O-])O.[Na+]>O>[Cl:1][C:2]1[C:3]2[N:13]([CH3:14])[C:26]([C:25]3[CH:29]=[CH:30][CH:31]=[CH:32][C:24]=3[S:23][CH2:21][CH3:22])=[N:12][C:4]=2[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 516892Sodium Bicarbonate2×HCID 679812702-Ethylsulfanylbenzoic acid hydrochloride2×HCID 680910673-Chloro-N2-methyl-5-(trifluoromethyl)-1,2-benzenediamine

Product 1

HCID 679843507-chloro-2-(2-ethylsulfanylphenyl)-1-methyl-5-trifluoromethyl-1H-benzimidazoleYield 28.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 3-chloro-N2-methyl-5-trifluoromethylbenzene-1,2-diamine (1.12 g) and THF (5 ml), 2-ethylsulfanylbenzoic acid hydrochloride (1.00 g) was added under ice-cooling, heated to room temperature, and stirred for 1 hour. Sodium hydrogen carbonate (0.46 g) was added thereto, and then the reaction mixture was allowed to stand overnight. The reaction mixture was heated to 66° C., and stirred under reflux for 1.5 hours. After the mixture was cooled to room temperature, 2-ethylsulfanylbenzoic acid hydrochloride (0.5 g) was added at room temperature. After the reaction mixture was allowed to stand at room temperature overnight, sodium hydrogen carbonate (1.00 g) was added, and stirred. The reaction mixture was ice-cooled, and then water was added under ice-cooling, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give 0.48 g of 7-chloro-2-(2-ethylsulfanylphenyl)-1-methyl-5-trifluoromethyl-1H-benzimidazole (hereinafter referred to as Present Compound 71).

Workup

  1. additionwas added under ice-
  2. temperaturecooling
  3. waitto stand overnight
  4. temperatureThe reaction mixture was heated to 66° C.
  5. stirringstirred
  6. temperatureunder reflux for 1.5 hours
  7. temperatureAfter the mixture was cooled to room temperature
  8. waitto stand at room temperature overnight
  9. stirringstirred
  10. temperaturecooled
  11. temperaturecooling
  12. extractionextracted with ethyl acetate
  13. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a5f7ce51ae834e4f8fad30d875aec537
Source dataset
uspto-grants-2014_10
Patent number
US08853238B2

Reaction notes

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