3,4,5-Trimethoxybenzaldehyde → 5,6,7-Trimethoxynaphthalene-2-carbonitrile

Participants

Reaction Steps

2.0 M Lithium diisopropylamide (2.55 mL) was added dropwise to dry THF (5 mL) at −78° C. under an argon atmosphere, and the mixture was stirred for 30 minutes. A solution of 3-cyanopropionaldehyde dimethylacetal (672 mg) in dry THF (5 mL) was then added dropwise to the mixture, and the resulting mixture was stirred at −78° C. for 1 hour. A solution of 3,4,5-trimethoxybenzaldehyde (1.0 g) in dry THF (5 mL) was then added dropwise to the reaction mixture. After stirring at room temperature for 1 hour, a saturated aqueous solution of ammonium chloride was added to the reaction mixture to conduct extraction with ethyl acetate. The resultant organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resultant residue was dissolved in methanol (6 mL), sulfuric acid (1 mL) was slowly added to the solution, and the mixture was stirred at 100° C. for 1 hour. The reaction mixture was weakly alkalified with a 4 M aqueous solution of potassium hydroxide at 0° C. to conduct extraction with chloroform. The resultant organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:3 to 1:1) to obtain the title compound.

Provenance & Evidence