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

HRID 1352947Notes

Reaction equation

HRID 1352947 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]([C:20]3[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:22][CH:21]=3)[CH2:12][C:13](O)([C:15]([F:18])([F:17])[F:16])[N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]([C:20]3[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:27])=[O:28])=[CH:22][CH:21]=3)[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 107888462-(3-fluoro-4-methoxyphenyl)-4-hydroxy-1-(4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazole

Product 1

HCID 101365091h-Imidazole,2-(3-fluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-Yield 65%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-(3-fluoro-4-methoxyphenyl)-4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazole from Step 2 (3.4 g, 7.9 mmol) and p-toluenesulfonic acid monohydrate (700 mg) in toluene (200 mL) was heated to reflux for 72 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 (3.6 g) was purified by chromatography on silica gel using toluene/ethyl acetate (8/2) to give pure 2-(3-fluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole (2.12 g, 65%) as a white solid: mp (DSC) 182° C. Anal. Calc'd. for C18H14N2SO3F4: C, 52.17; H, 3.41; N, 6.76; S, 7.74. Found: C, 52.56; H, 3.65; N, 6.53; S, 8.01.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 72 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 (3.6 g) was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-55009a1af6f44792afd427f6bbe0a655
Source dataset
uspto-grants-2007_05
Patent number
US07220770B2

Reaction notes

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