Trifluoroacetic acid → 3,5-dimethyl-2-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole

HRID 1189551Notes

Reaction equation

HRID 1189551 reaction equation
[CH3:1][C:2]1[NH:3][CH:4]=[C:5]([CH3:7])[CH:6]=1.[N:8]1([S:13]([C:16]2[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=2[CH:18]=O)(=[O:15])=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9]1.[OH-].[Na+].C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C.C(=O)(O)[O-].[Na+]>C(O)C(F)(F)F>[CH3:1][C:2]1[NH:3][CH:4]=[C:5]([CH3:7])[C:6]=1[CH2:18][C:17]1[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=1[S:13]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)(=[O:14])=[O:15].[CH3:7][C:5]1[CH:6]=[C:2]([CH3:1])[NH:3][C:4]=1[CH2:18][C:17]1[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=1[S:13]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)(=[O:14])=[O:15]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 395392,4-DimethylpyrroleHCID 516892Sodium BicarbonateHCID 573845822-(Pyrrolidin-1-ylsulfonyl)benzaldehyde

Product 2

HCID 583109223,5-dimethyl-2-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrroleYield 17.3%HCID 583109502,4-dimethyl-3-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrroleYield 6.14%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2,4-dimethyl-1H-pyrrole (2.0 ml, 19.42 mmol) and 2-(pyrrolidin-1-ylsulfonyl)benzaldehyde (4.65 g, 19.42 mmol) in trifluoroethanol (48.6 ml) and 12.5 sodium hydroxide (1.554 ml, 19.42 mmol) was heated at 50° C. for 1 h. The mixture was poured into ice and the resulting murky solution was decanted. The remaining residue was taken up in benzene and concentrated under vacuum. This residue was diluted in DCM (48.6 ml) and cooled to 0° C. To this solution, were added TFA (7.48 ml, 97 mmol) and triethylsilane (31.0 ml, 194 mmol). This mixture was heated at reflux (50° C.) for 15 min and poured into a mixture of ice and saturated solution of sodium bicarbonate. The mixture was extracted with dichloromethane (100 ml×2). The organic layers were combined, washed with brine (50 ml), dried, filtered, and concentrated to give an oil. Purification of the oil by column chromatography (0 to 20% ethyl acetate in hexanes) gave 2,4-dimethyl-3-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole (380.0 mg, 1.193 mmol, 6.14% yield,) [Rf=0.73 (20% ethyl acetate in hexanes)] and 3,5-dimethyl-2-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrole (1.07 g, 3.36 mmol, 17.30% yield) [Rf=0.63 (20% ethyl acetate in hexanes)].

Workup

  1. additionThe mixture was poured into ice
  2. customthe resulting murky solution was decanted
  3. concentrationconcentrated under vacuum
  4. additionThis residue was diluted in DCM (48.6 ml)
  5. temperaturecooled to 0° C
  6. temperatureThis mixture was heated
  7. temperatureat reflux (50° C.) for 15 min
  8. extractionThe mixture was extracted with dichloromethane (100 ml×2)
  9. washwashed with brine (50 ml)
  10. customdried
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give an oil
  14. customPurification of the oil by column chromatography (0 to 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c23db15ea34a4f499c7e76b28988a431
Source dataset
uspto-grants-2014_03
Patent number
US08674115B2

Reaction notes

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