Tetrahydrofuran → 4-Methyl-2-(2,5-dimethylpyrrol-1-yl)-6-(4-(2,5-dimethylpyrrol-1-yl)butyl)pyridine

Participants

Reaction Conditions

Reaction Steps

A solution of 297 mg (1.49 mmol) of 4,6-dimethyl-2-(2,5-dimethylpyrrol-1-yl)pyridine (from Example 53, Step A) in 1.5 mL of ethyl ether was added to a -20° C. solution prepared from 3.0 mL of ethyl ether and 1.2 mL (1.7 mmol) of 1.4 M n-butyllithium in hexane. The mixture was stirred for 1 h at -20 to -15° C. with the formation of a preciptate. Tetrahydrofuran (1.0 mL) was added, the resulting orange-red solution was cooled to .BECAUSE.45° C., and 400 mg (1.85 mmol) of 1-(3-bromopropyl)-2,5-dimethylpyrrole (S. P. Bruekelman, S. E. Leach, G. D. Meakins, and M. D. Tirel, J. Chem. Soc., Perkin Trans. 1, 1984, 2801-7) was added in one portion. The mixture was allowed to warm to 10° C. over 1.75 h, quenched with 10 mL of saturated aqueous ammonium chloride, and extracted with 20 mL of ethyl acetate. The organic layer was washed with 10 mL of saturated aqueous sodium chloride, dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on 50 g of silica gel, eluting with 1.2 L of 5% ethyl acetate in hexane to give 402 mg (80% yield) of 4-methyl-2-(2,5-dimethylpyrrol-1-yl)-6-(4-(2,5-dimethylpyrrol-1-yl)butyl)pyridine as an almost colorless oil.

Provenance & Evidence