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

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Reaction Conditions

Reaction Steps

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)].

Provenance & Evidence