3-Bromo-1,1,1-trifluoro-2-propanone → 2-[4-Hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1h-imidazol-2-yl]thiophene

HRID 52360Notes

Reaction equation

HRID 52360 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[NH:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(=O)(O)[O-].[Na+].Br[CH2:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28]>C(O)(C)C>[OH:31][C:26]1([C:27]([F:30])([F:29])[F:28])[CH2:25][N:11]([C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:9]=2)[C:12]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[N:13]1

Participants

5

Reactant 3

HCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 516892Sodium BicarbonateHCID 178504800HCID 178504800, compound

Product 1

HCID 229979092-[4-Hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1h-imidazol-2-yl]thiopheneYield 39.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a mixture of the amidine of step 1 (2.0 g, 7.1 mmol) and sodium bicarbonate (1.2 g, 14.3 mmol) in isopropanol (200 ml), 3-bromo-1,1,1-trifluoroacetone (1.1 ml, 10.7 mmol) was added. After heating at 80°-85° C. for 16 hours, the reaction mixture was cooled and filtered. The residue was washed with methylene chloride and the combined organic fractions were dried over sodium sulfate, filtered and concentrated. The crude mixture (25.7 g) was chromatographed (silica gel, ethyl acetate/hexane 55/45) to give the 4,5-dihydroimidazole (1.1 g, 38%) as a white solid: mp (DSC) 214° C. Anal. Calc'd. for C15H13N2S2O3F3 : C, 46.15, H, 3.36, N, 7.18, S, 16.43 Found C, 46.09, H, 3.26, N, 7.07, S, 16.71.

Workup

  1. additionwas added
  2. temperatureAfter heating at 80°-85° C. for 16 hours
  3. temperaturethe reaction mixture was cooled
  4. filtrationfiltered
  5. washThe residue was washed with methylene chloride
  6. dry with materialthe combined organic fractions were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude mixture (25.7 g) was chromatographed (silica gel, ethyl acetate/hexane 55/45)

Sources & evidence

ORD record
ord-e4c19e22268f4ddbb076077dcf07809e
Source dataset
uspto-grants-1997_04
Patent number
US05616601

Reaction notes

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