p-Toluenesulfonic acid monohydrate → 3-[1-(4-Methanesulfonyl-phenyl)-4-trifluoromethyl-1H-imidazol-2-yl]-5-methyl-pyridine

HRID 52358Notes

Reaction equation

HRID 52358 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]2[N:9]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH2:10][C:11](O)([C:13]([F:16])([F:15])[F:14])[N:12]=2)[CH:7]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]2[N:9]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[CH:10]=[C:11]([C:13]([F:15])([F:16])[F:14])[N:12]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 22998202HCID 22998202, compound

Product 1

HCID 108098553-[1-(4-Methanesulfonyl-phenyl)-4-trifluoromethyl-1H-imidazol-2-yl]-5-methyl-pyridineYield 46,922%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 3-methyl-5-[4-hydroxy-1-[4-(methylsulfonyl) phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine from step 4 (3.8 g, 0.0095 mmol) and p-toluenesulfonic acid monohydrate (0.91 g, 0.0048 mmol) in 150 mL of toluene was heated to reflux for 24 hours. The reaction mixture was cooled and the solvent was removed under reduced pressure. The residue was partitioned between water and methylene chloride. The organic layer was washed with water, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo and the crude product was purified by chromatography on silica gel (ethyl acetate/acetone, 98:2) to give 3-methyl-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine as a yellow solid (1.7 g, 47%): mp (DSC) 196°-198° C; Anal. Calc'd. for C17H14F3N3O2S: C, 53.54, H, 3.70, N, 11.02, 8.41. Found: C, 53.50, H, 3.65, 10.82, S, 8.55.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 hours
  3. temperatureThe reaction mixture was cooled
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was partitioned between water and methylene chloride
  6. washThe organic layer was washed with water, saturated sodium bicarbonate solution and brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customThe filtrate was evaporated in vacuo
  10. customthe crude product was purified by chromatography on silica gel (ethyl acetate/acetone, 98:2)

Sources & evidence

ORD record
ord-64c97998ba934d34b7bd39fd98721a55
Source dataset
uspto-grants-1997_04
Patent number
US05616601

Reaction notes

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