Ethyl Acetate → 1-((1,3-Dioxolan-2-yl)methyl)-1,7-naphthyridin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a suspension of 6.0 g of 1,7-naphthyridin-2(1H)-one in 60 mL of N,N-dimethylformamide, 2.5 g of 60% sodium hydride was added at room temperature, and the mixture was stirred at 50 to 60° C. for 1 hour. Thereto was added 6.4 mL of 2-bromomethyl-1,3-dioxolan, the temperature was increased to 90 to 95° C., and the reaction mixture was stirred for 2 hours 30 minutes. The temperature was further increased to 95 to 100° C., and the mixture was stirred for 4 hours. Thereto were added 0.82 g of 60% sodium hydride and 2.1 mL of 2-bromomethyl-1,3-dioxolan and the mixture was further stirred at the same temperature for 2 hours. Thereto were added 0.49 g of 60% sodium hydride and 1.3 mL of 2-bromomethyl-1,3-dioxolan and the mixture was stirred at 90 to 100° C. for 2 hours. Thereto were further added 0.49 g of 60% sodium hydride and 1.3 mL of 2-bromomethyl-1,3-dioxolan and the mixture was stirred at the same temperature for 4 hours. The reaction mixture was cooled to 5° C., and ethyl acetate and ice water were then added thereto. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using gradient elution with hexane:ethyl acetate=100:0 to 0:100 and then, using gradient elution with chloroform:methanol=100:0 to 90:10 to obtain 3.1 g of 1-(1,3-dioxolan-2-ylmethyl)-1,7-naphthyridin-2(1H)-one as a brown solid.

Provenance & Evidence