3-Bromo-1,1,1-trifluoro-2-propanone → 2-Methyl-6-[4-hydroxy-1-[4-(methylsulfonyl) phenyl]-4-(trifluoromethyl)-4,5-dihydro-1h-imidazol-2-yl]pyridine

HRID 1166364Notes

Reaction equation

HRID 1166364 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8](=[NH:20])[NH:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)[N:3]=1.C(=O)(O)[O-].[Na+].Br[CH2:27][C:28](=[O:33])[C:29]([F:32])([F:31])[F:30]>C(O)(C)C>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[N:9]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=3)[CH2:27][C:28]([OH:33])([C:29]([F:32])([F:31])[F:30])[N:20]=2)[N:3]=1

Participants

5

Reactant 3

HCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 516892Sodium BicarbonateHCID 178425254HCID 178425254, compound

Product 1

HCID 229977732-Methyl-6-[4-hydroxy-1-[4-(methylsulfonyl) phenyl]-4-(trifluoromethyl)-4,5-dihydro-1h-imidazol-2-yl]pyridineYield 21%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
82.5 °C

Procedure

To a mixture of the amidine of Step 1 (4.9 g, 16.95 mmol) and sodium bicarbonate (2.85 g, 33.9 mmol) in isopropanol (300 ml), 3-bromo-1,1,1-trifluoroacetone (2.65 ml, 25.4 mmol) was added. After heating at 80-85° C. for 24 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 (9 g) was purified by chromatography (silica gel, ethyl acetate/isopropanol/ammonium hydroxide 95/5/0.5) to give 2-methyl-6-[4-hydroxy-1-[4-(methylsulfonyl) phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine (1.4 g, 21%) as a white solid: Anal. Calc'd. for C17H16N3SO3F3: C, 51.12, H, 4.02, N, 10.52. Found: C, 51.43, H, 3.96, N, 10.06.

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was cooled
  3. filtrationfiltered
  4. washThe residue was washed with methylene chloride
  5. dry with materialthe combined organic fractions were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude mixture (9 g) was purified by chromatography (silica gel, ethyl acetate/isopropanol/ammonium hydroxide 95/5/0.5)

Sources & evidence

ORD record
ord-123a851bae874879bf12c16efa34c050
Source dataset
uspto-grants-2003_09
Patent number
US06613789B2

Reaction notes

Loading…