Reaction #921

Reaction equation

ammonium chloride

n-butyllithium

N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide

N,N-dimethylcarbamyl chloride

HCl

→

title compound

Yield 50.2%

3-[[-(1,1-Dimethylethyl)amino]sulfonyl]-N,N,1-trimethyl-1H-pyrrole-2-carboxamide

Yield 50.2%

Solvents

—

hexanes

THF

THF

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   Temperatureto maintain the temperature below -65° C
3. 3
   Temperatureto warm to room temperature
4. 4
   workup.STIRRINGstir for ca. 1.5 hours
5. 5
   TemperatureThe reaction mixture was cooled to ca. 5° C.
6. 6
   workup.STIRRINGThe reaction mixture was stirred for ca. 15 minutes
7. 7
   Otherthe aqueous phase was separated from the THF phase
8. 8
   Extractionextracted with ethyl acetate
9. 9
   WashThe combined THF and ethyl acetate extracts were washed with brine
10. 10
    Dryingdried (MgSO4)
11. 11
    Concentrationconcentrated in vacuo to an oil
12. 12
    OtherThe oil was chromatographed on silica with (20% ethyl acetate/80% n-butyl chloride)

Procedure

To a solution of 6.48 g (30 mmol) of N-(1,1-dimethylethyl)-1-methyl-1H-pyrrole-3-sulfonamide in 150 mL THF under a nitrogen atmosphere cooled to -78° C. was added dropwise, at such a rate as to keep the temperature below -60° C., 25 mL (61.5 mmol) 2.46M n-butyllithium in hexanes. The reaction mixture was stirred at -78° C. for ca. 30 minutes. To the reaction mixture was added dropwise a solution of 3.1 mL (33 mmol) of N,N-dimethylcarbamyl chloride in 10 mL of THF at such a rate as to maintain the temperature below -65° C. The reaction mixture was allowed to warm to room temperature and stir for ca. 1.5 hours. The reaction mixture was cooled to ca. 5° C. and 60 mL of 50% ammonium chloride solution was added. The reaction mixture was stirred for ca. 15 minutes. The pH was adjusted to ca. 3 with 1N HCl (ca. 30 mL), and the aqueous phase was separated from the THF phase and extracted with ethyl acetate. The combined THF and ethyl acetate extracts were washed with brine, dried (MgSO4) and concentrated in vacuo to an oil. The oil was chromatographed on silica with (20% ethyl acetate/80% n-butyl chloride) affording 4.33 g of the title compound as a pale yellow solid.

Source