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

HRID 1352969

Reaction equation

HRID 1352969 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[NH:13])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(=O)(O)[O-].[Na+].Br[CH2:26][C:27](=[O:32])[C:28]([F:31])([F:30])[F:29]>C(O)(C)C>[OH:32][C:27]1([C:28]([F:31])([F:30])[F:29])[CH2:26][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[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:13]1

Participants

5

Reactant 3

HCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 516892Sodium BicarbonateHCID 178504797HCID 178504797, compound

Product 1

HCID 229979882-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridineYield 18%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a mixture of the amidine of step 1 (4.4 g, 16 mmol) and sodium bicarbonate (2.7 g, 32 mmol) in isopropanol (400 ml), 3-bromo-1,1,1-trifluoroacetone (2.5 ml, 24 mmol) was added. After heating at 75–80° 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 product (16.2 g) was purified by chromatography (silica gel, ethyl acetate/toluene 1/1) to give 2-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine (1.1 g, 18%) as a white solid: mp 195–198° C. Anal. Calc'd. for C16H14N3SO3F3: C, 49.87; H, 3.66; N, 10.90. Found: C, 50.13; H, 3.66; N, 10.30.

Workup

  1. additionwas added
  2. temperatureAfter heating at 75–80° C. for 24 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 product (16.2 g) was purified by chromatography (silica gel, ethyl acetate/toluene 1/1)

Sources & evidence

ORD record
ord-6eb382aa29f548549edf79ce99cf12d1
Source dataset
uspto-grants-2007_05
Patent number
US07220770B2

Linked notes

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