Sulfuric Acid → 3-(3,4-Dimethoxyphenyl)-4,4-diethoxy-2-ethoxycarbonylbutyric acid ethyl ester

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Reaction Conditions

Reaction Steps

A solution of methyl methylsulfinyl-methylsulfide (2.34 g, 18.81 M) in dry tetrahydrofuran (24 ml) was cooled to 0° C., and to this solution a solution of butyl lithium in hexane (18.81 mM) was added dropwise, which was stirred at the temperature as it was for 30 minutes. Then, the solution was cooled to −78° C., and a solution of 3,4-dimethoxybenzylidene malonic acid diethyl ester (5.00 g, 15.47 mM) in dry tetrahydrofuran (2 ml) was added. The solution obtained was gradually warmed to room temperature, was poured into an aqueous solution of ammonium chloride, extracted with diethylether, and after drying the organic extract over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure to obtain a crude product (6.70 g) of a brown oil of 3-(3,4-dimethoxyphenyl)-2-ethoxycarbonyl-4-methylsulfinyl-4-methylthio butyric acid ethyl ester. This was dissolved in dry ethanol (25 ml), and then ethyl orthoformate (3.09 g, 20.88 mM) and sulfuric acid (0.25 ml) were added and stirred at room temperature for 3 days. This solution was poured into an aqueous solution of sodium bicarbonate under cooling on ice, extracted with diethylether, and after the organic extract was dried, the solvent was evaporated under reduced pressure to obtain an oily crude product. The crude product was purified by flash chromatography (SiO2: eluted with ethyl acetate). It was concentrated under reduced pressure and dried to obtain a yellow oil of 3-(3,4-dimethoxyphenyl)-4,4-diethoxy-2-ethoxycarbonyl butyric acid ethyl ester (5.08 g, yield 79.5%).

Provenance & Evidence