Reaction #74171

Reaction equation

isobutyl bromide

N-[3-(4-bromo-1H-pyrazol-3-yl)-2,4-difluorophenyl]-2,5-difluorobenzene-sulfonamide

isobutyl bromide

→

N-{3-[4-bromo-1-(2-methyl propyl)-1H-pyrazol-5-yl]-2,4-difluorophenyl}-2,5-difluoro-benzenesulfonamide

Solvents

dichloromethane

sodium hydroxide

Conditions

Workup

1. 1
   workup.STIRRINGafter 18 h additional stirring the reaction
2. 2
   OtherThe phases were separated
3. 3
   Washthe organic layer was washed with water
4. 4
   Dryingdried over anhydrous sodium sulfate
5. 5
   Concentrationconcentrated
6. 6
   OtherThe crude residue was purified by flash chromatography (eluant: dichloromethane)

Procedure

To the residue, dissolved in dichloromethane (10 mL), isobutyl bromide (1 mL, 9 mmol) and tetrabutylammonium bromide (0.16 g, 0.5 mmol) in 7 N sodium hydroxide (10 mL) were added and the mixture was vigorously stirred at room temperature. After 2 h, only N-[3-(4-bromo-1H-pyrazol-3-yl)-2,4-difluorophenyl]-2,5-difluorobenzene-sulfonamide was present. Upon addition of more isobutyl bromide (3 mL, 27 mmol) and tetrabutylammonium bromide (0.45 g, 1.4 mmol) and after 18 h additional stirring the reaction was completed. The phases were separated and the organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated. The crude residue was purified by flash chromatography (eluant: dichloromethane). First the regioisomer N-{3-[4-bromo-1-(2-methyl propyl)-1H-pyrazol-5-yl]-2,4-difluorophenyl}-2,5-difluoro-benzenesulfonamide (0.065 g, 0.13 mmol) was isolated, then the title product was obtained as a white solid (0.12 g, 0.2 mmol, 15% four steps).

Source