3-Bromo-1,1,1-trifluoro-2-propanone → 2-(3-fluoro-4-methoxyphenyl)-4-hydroxy-1-(4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazole

HRID 1352946Notes

Reaction equation

HRID 1352946 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10](=[NH:22])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].C(=O)(O)[O-].[Na+].Br[CH2:29][C:30](=[O:35])[C:31]([F:34])([F:33])[F:32]>C(O)(C)C>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:19])=[O:20])=[CH:14][CH:13]=3)[CH2:29][C:30]([OH:35])([C:31]([F:34])([F:33])[F:32])[N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]

Participants

5

Reactant 3

HCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 516892Sodium BicarbonateHCID 178491240HCID 178491240, compound

Product 1

HCID 107888462-(3-fluoro-4-methoxyphenyl)-4-hydroxy-1-(4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazoleYield 64%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a mixture of 3-fluoro-4-methoxy-N-[4-(methylsulfonyl)phenyl]benzenecarboximidamide from Step 1 (4.15 g, 12.9 mmol) and sodium bicarbonate (2.16 g, 25.8 mmol) in isopropanol (150 mL), 3-bromo-1,1,1-trifluoroacetone (4.8 mL, 45 mmol) was added. After heating the reaction mixture at 70–75° C. for 20 hours, the solvent was removed. The residue was redissolved in methylene chloride and washed with water. The organic fractions were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude mixture (7.8 g) was purified by chromatography (silica gel, toluene/ethyl acetate, 7/3) to give 2-(3-fluoro-4-methoxyphenyl)-4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazole (3.54 g, 64%) as a white solid: mp (DSC) 210° C. Anal. Calc'd. for C18H16N2SO4F4.0.1 PhCH3: C, 50.86; H, 3.83; N, 6.34. Found: C, 50.61; H. 3.64; N, 6.16.

Workup

  1. additionwas added
  2. temperatureAfter heating the reaction mixture at 70–75° C. for 20 hours
  3. customthe solvent was removed
  4. dissolutionThe residue was redissolved in methylene chloride
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude mixture (7.8 g) was purified by chromatography (silica gel, toluene/ethyl acetate, 7/3)

Sources & evidence

ORD record
ord-6ffd52bbf12548878eb54c7d45619b2d
Source dataset
uspto-grants-2007_05
Patent number
US07220770B2

Reaction notes

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