p-Toluenesulfonic acid monohydrate → 1-(4-Methanesulfonyl-phenyl)-2-thiophen-3-yl-4-trifluoromethyl-1H-imidazole

HRID 1166379Notes

Reaction equation

HRID 1166379 reaction equation
O[C:2]1([C:22]([F:25])([F:24])[F:23])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([CH3:16])(=[O:15])=[O:14])=[CH:9][CH:8]=2)[C:4]([C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)=[N:3]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:16][S:13]([C:10]1[CH:9]=[CH:8][C:7]([N:5]2[CH:6]=[C:2]([C:22]([F:24])([F:25])[F:23])[N:3]=[C:4]2[C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)=[CH:12][CH:11]=1)(=[O:15])=[O:14]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrate2×HCID 22998113HCID 22998113, compound

Product 1

HCID 106192741-(4-Methanesulfonyl-phenyl)-2-thiophen-3-yl-4-trifluoromethyl-1H-imidazoleYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of the 4,5-dihydro-imidazole of step 2 (1.5 g, 3.8 mmol) and p-toluenesulfonic acid monohydrate (0.30 g, 1.5 mmol) in toluene (250 ml) was heated to reflux for 40 hours. An additional p-toluenesulfonic acid monohydrate (0.15 g, 0.78 mmol) was added. The reaction mixture was heated to reflux for 18 hours. The reaction mixture was cooled and the solvent removed under reduced pressure. The crude mixture (3.5 g) was purified by chromatography on silica gel using ethyl acetate/toluene (55/45) to give pure 3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]thiophene (0.90 g, 64%) as a white solid: mp 194-197° C. Anal. Calc'd. for C15H11N2S2O2F3: C, 48.38, H, 2.98, N. 7.52, S, 17.22. Found: C, 48.74, H, 2.98, N. 7.56, S, 17.45

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 40 hours
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 18 hours
  5. temperatureThe reaction mixture was cooled
  6. customthe solvent removed under reduced pressure
  7. customThe crude mixture (3.5 g) was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-00f718970968441990af442f1d319707
Source dataset
uspto-grants-2003_09
Patent number
US06613789B2

Reaction notes

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