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

HRID 1166361Notes

Reaction equation

HRID 1166361 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([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)=[CH:4][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][C:5]([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)=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 516892Sodium BicarbonateHCID 178425634HCID 178425634, compound

Product 1

HCID 229981692-Methyl-5-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1h-imidazol-2-yl]pyridineYield 46.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
82.5 °C

Procedure

To a mixture of the amidine of Step 1 (9.8 g, 33.9 mmol) and sodium bicarbonate (5.7 g, 67.8 mmol) in isopropanol (700 ml), 3-bromo-1,1,1-trifluoroacetone (5.3 ml, 50.8 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 material (25.7 g) was purified by chromatography (silica gel, ethyl acetate/acetone, 98/2) to give 2-methyl-5-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine (6.3 g, 46%) as a white solid: Anal. Calc'd. for C17H16N3SO3F3: C, 50.55, H, 4.12, N, 10.40. Found: C, 50.51, H, 3.91, N, 10.25.

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 material (25.7 g) was purified by chromatography (silica gel, ethyl acetate/acetone, 98/2)

Sources & evidence

ORD record
ord-1a5a1fa22af147d4a7ebb3f58309e37e
Source dataset
uspto-grants-2003_09
Patent number
US06613789B2

Reaction notes

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