p-Toluenesulfonic acid monohydrate → 1h-Imidazole,2-(3-chloro-4-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-

HRID 52314Notes

Reaction equation

HRID 52314 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)[CH2:11][C:12](O)([C:14]([F:17])([F:16])[F:15])[N:13]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:26])=[O:27])=[CH:21][CH:20]=3)[CH:11]=[C:12]([C:14]([F:17])([F:15])[F:16])[N:13]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 117970112-(3-chloro-4-methylphenyl)-4-hydroxy-1-(4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazole

Product 1

HCID 105019571h-Imidazole,2-(3-chloro-4-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-Yield 95%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-(3-chloro-4-methylphenyl)-4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazole from Step 2 (725 mg, 1.7 mmol) and p-toluenesulfonic acid monohydrate (150 mg) in toluene (40 mL) was heated to reflux for 48 hours. The reaction mixture was cooled and the solvent removed under reduced pressure. The crude residue was redissolved in methylene chloride and washed with water, aqueous sodium bicarbonate and brine. After drying (Na2SO4), filtration and concentration in vacuo, the crude mixture (860 mg) was chromatographed on silica gel using toluene/ethyl acetate 1/1 to give pure 2-(3-chloro-4-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole (660 mg, 95%) as a white solid: mp(DSC) 206° C. Anal. Calc'd. for C18H14N2SO2F3Cl: C, 52.12, H, 3.40, N, 6.75, S, 7.73. Found: C, 52.24, H, 3.45, N, 6.64, S, 7.83.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 48 hours
  3. temperatureThe reaction mixture was cooled
  4. customthe solvent removed under reduced pressure
  5. dissolutionThe crude residue was redissolved in methylene chloride
  6. washwashed with water, aqueous sodium bicarbonate and brine
  7. customAfter drying
  8. filtration(Na2SO4), filtration and concentration in vacuo
  9. customthe crude mixture (860 mg) was chromatographed on silica gel

Sources & evidence

ORD record
ord-740ebae929b24a659916140ab4c4674c
Source dataset
uspto-grants-1997_04
Patent number
US05616601

Reaction notes

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