Triethylborane → 4-[2-(6-Methyl-pyridin-3-yl)-4-trifluoromethyl-imidazol-1-yl]-benzenesulfonamide

HRID 52354

Reaction equation

HRID 52354 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([C:17]3[CH:22]=[CH:21][C:20]([S:23](C)(=[O:25])=[O:24])=[CH:19][CH:18]=3)[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:12]=2)=[CH:4][N:3]=1.C([Mg]Cl)CCC.C(B(CC)CC)C.C([O-])(=O)C.[Na+].[NH2:45]OS(O)(=O)=O>O1CCCC1.O>[CH3:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2[N:9]([C:17]3[CH:22]=[CH:21][C:20]([S:23]([NH2:45])(=[O:25])=[O:24])=[CH:19][CH:18]=3)[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:12]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 7357TriethylboraneHCID 76284hydroxylamine-O-sulfonic acidHCID 517045Sodium AcetateHCID 101778455-[1-(4-Methanesulfonyl-phenyl)-4-trifluoromethyl-1H-imidazol-2-yl]-2-methyl-pyridineHCID 178418265HCID 178418265, compound

Product 1

HCID 102932424-[2-(6-Methyl-pyridin-3-yl)-4-trifluoromethyl-imidazol-1-yl]-benzenesulfonamideYield 12.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a clear solution of Example 33 (2.4 g, 6.3 mmol) in tetrahydrofuran (60 ml) at 0° C., n-BuMgCl (2M solution in THF, 15.7 ml, 31.5 mmol) was added over 10 minutes. After stirring for additional 20 minutes, the ice bath was removed and the solution was stirred for 2 hours. The reaction mixture was recooled to 0° C. and triethylborane (1M solution in THF, 38 ml, 38 mmol) was added. After stirring for 1 hour, the reaction was heated to reflux for 72 hours. The reaction mixture was cooled to room temperature and treated with aqueous sodium acetate (5.5 g in 22 ml water). After stirring for 5 minutes, solid hydroxylamine-O-sulfonic acid (5.5 g) was added and the mixture stirred for 24 hours. The reaction mixture was diluted with water and extracted with ether. The ethereal layer was dried over sodium sulfate, filtered and concentrated. The crude solid (13.3 g) was chromatographed (silica gel, hexane/isopropanol, 7/3) to give 4-[2-(6-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide (298 mg, 12%): mp (DSC) 203° C. Anal. Calc'd. for C16H13N4SO2F3 0.25H2O: C, 49.68, H, 3.52 N, 14.48, S, 8.29. Found: C, 49.88, H, 3.39, N, 13.94, S, 8.47.

Workup

  1. customthe ice bath was removed
  2. stirringthe solution was stirred for 2 hours
  3. customwas recooled to 0° C.
  4. stirringAfter stirring for 1 hour
  5. temperaturethe reaction was heated
  6. temperatureto reflux for 72 hours
  7. stirringAfter stirring for 5 minutes
  8. stirringthe mixture stirred for 24 hours
  9. extractionextracted with ether
  10. dry with materialThe ethereal layer was dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude solid (13.3 g) was chromatographed (silica gel, hexane/isopropanol, 7/3)

Sources & evidence

ORD record
ord-b3dd10895ff747d79bcb76f20cd8bfa5
Source dataset
uspto-grants-1997_04
Patent number
US05616601

Linked notes

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