1-Methylimidazole → (1-Methyl-1H-imidazol-5-yl)(pyridin-3-yl)methanone

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a heat-gun dried flask containing 1-methyl-1H-imidazole (1.55 mL, 19.5 mmol) and THF (20 mL) at −78° C. was added 1.6 M n-BuLi in hexane (12.8 mL, 20.5 mmol). After stirring at −78° C. for 30 min, chlorotriethylsilane (3.3 mL, 19.7 mmol) in neat was introduced slowly. The mixture was stirred at −78° C. for 30 min. 1.6 M n-BuLi in hexane (12.8 mL, 20.5 mmol) was added, and the mixture was stirred for 45 min. A solution of N-methoxy-N-methylnicotinamide (2.70 g, 16.2 mmol, Intermediate 10, step a) in THF (20 mL) was added via cannula, and the mixture was stirred at −78° C. to room temperature for 2 hours. The reaction was quenched with NH4Cl (aqueous), the organic layer was separated, and the aqueous layer was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered, concentrated, and purified by flash column chromatography (40 g silica gel column, 50-100% EtOAc in heptane, then 5-10% MeOH in CH2Cl2) to obtain the title compound as an off-white solid.

Herkunft & Nachweise