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

HRID 1352990Notes

Reaction equation

HRID 1352990 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 47%

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, 9.5 mmol) and p-toluenesulfonic acid monohydrate (0.91 g, 4.8 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 flash 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 C17H14F3N3P2S: C, 53.54, H, 3.70, N, 11.02, S, 8.41. Found: C, 53.50, H, 3.65, N, 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 flash chromatography on silica gel (ethyl acetate/acetone, 98:2)

Sources & evidence

ORD record
ord-909ee85b28ed4303952f7487fc9bc9e0
Source dataset
uspto-grants-2007_05
Patent number
US07220770B2

Reaction notes

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