1-Methylimidazole → (6-Fluoropyridin-3-yl)(1-methyl-1H-imidazol-5-yl)methanone

Participants

Reaction Conditions

Reaction Steps

To a 250-mL round-bottom flask containing 1-methyl-1H-imidazole (1.74 g, 21.2 mmol) and THF (50 mL) at −78° C. under nitrogen was added n-BuLi in hexane (2.5 M, 9.8 mL, 24.5 mmol) dropwise. The resulting mixture was stirred for 1 hour at −78° C., and Et3SiCl (3.20 g, 21.2 mmol) was added. The mixture was stirred for an additional 1 hour at −78° C., and a second portion of n-BuLi (2.5 M, 8.5 mL, 21.3 mmol) was added. After stirring for an additional 1 hour at −78° C., 6-fluoro-N-methoxy-N-methylpyridine-3-carboxamide (3.00 g, 16.3 mmol, Intermediate 21, step b) was added. The mixture was stirred at −78° C. and then allowed to warm up to room temperature. The stirring was continued for 1 hour at room temperature, and then the reaction was quenched by the addition of 20 mL of water. The mixture was diluted with 100 mL of water. The organic layer was separated, and the aqueous layer was extracted with 3×50 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by chromatography (silica gel column, 1:4 EtOAc/petroleum ether) to give the title compound as a white solid.

Provenance & Evidence