Triethylborane → 4-[5-(4-fluorophenyl)-2-trifluoromethyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazol-4-yl]benzenesulfonamide

HRID 2231107Notes

Reaction equation

HRID 2231107 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:11]([C:21]([F:24])([F:23])[F:22])=[N:10][C:9]=2[C:25]2[CH:30]=[CH:29][C:28]([S:31](C)(=[O:33])=[O:32])=[CH:27][CH:26]=2)=[CH:4][CH:3]=1.C([Mg]Br)CCC.C(B(CC)CC)C.[NH2:48]OS(O)(=O)=O.C([O-])(=O)C.[Na+]>C1COCC1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:11]([C:21]([F:24])([F:23])[F:22])=[N:10][C:9]=2[C:25]2[CH:30]=[CH:29][C:28]([S:31]([NH2:48])(=[O:33])=[O:32])=[CH:27][CH:26]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 7357TriethylboraneHCID 76284hydroxylamine-O-sulfonic acidHCID 517045Sodium AcetateHCID 18463689HCID 18463689, compoundHCID 178418682HCID 178418682, compound

Product 1

HCID 184637044-[5-(4-fluorophenyl)-2-trifluoromethyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazol-4-yl]benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of the protected sulfone imidazole from step 1 (1.1 g, 2.0 mmol) in THF (15 ml) at 0° C. under an argon atmosphere, n-butyl magnesium bromide (n-BuMgBr) (2M solution in THF, 4.5 ml) was added and the temperature warmed to 25° C. over 30 minutes. Triethylborane (Et3B) (1M solution in THF, 9 ml) was added and the reaction was heated to reflux for 48 hours. The reaction mixture was cooled to 25° C. and a mixture of hydroxylamine-O-sulfonic acid (NH2OSO3H) (2 g) and sodium acetate (2 g) in water (8 ml) was added and rapidly stirred at 25° C. for 16 hours. Water (50 ml) was added and the product was extracted with ethyl acetate, dried (Na2SO4), and evaporated. The residue was purified by chromatography on silica gel using mixtures of ethyl acetate and toluene as the eluent to give 500 mg (45%) of the desired protected sulfonamide. The product was used directly in the next step.

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 48 hours
  3. temperatureThe reaction mixture was cooled to 25° C.
  4. additionwas added
  5. extractionthe product was extracted with ethyl acetate
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customThe residue was purified by chromatography on silica gel using mixtures of ethyl acetate and toluene as the eluent
  9. customto give 500 mg (45%) of the

Sources & evidence

ORD record
ord-abe1877597f94c818bf64ac68f6babb6
Source dataset
uspto-grants-2002_07
Patent number
US06426360B1

Reaction notes

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