Diisopropyl Ether → 1-Methyl-1-(3,5-dimethoxyphenyl)-2-methoxycarbonyl-3-carboxy-4-phenylbutadiene

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Reaction Steps

3,5-Dimethoxyacetophenone (246 g) and (E)-benzylidenesuccinic acid dimethyl ester (320 g) are dissolved in tert-butyl alcohol (1300 ml), and thereto is added potassium tert-butoxide (168.6 g) at room temperature, and the mixture is stirred. The mixture is allowed to cool to room temperature, and the mixture is further stirred at the same temperature for two hours. To the reaction mixture are added water (3 L) and diisopropyl ether (700 ml), and the aqueous layer is separated. To the remaining organic layer is added water, and the aqueous layer is separated. The aqueous layers are combined, and the pH value thereof is adjusted to pH 2-3 with conc. hydrochloric acid. The resulting oily product is extracted with ethyl acetate, and the extract is dried, and concentrated to give oily 1-methyl-1-(3,5-dimethoxyphenyl)-2-methoxycarbonyl-3-carboxy-4-phenylbutadiene (580 g) which is a mixture of (1Z,3E)-isomer and (1E,3E)-isomer. The oily product thus obtained is dissolved in diisopropyl ether-hexane, and the mixture is stirred at room temperature, and the precipitated crystals are collected. To the crystals is added ethyl acetate (1 L), and the mixture is heated at about 80° C., and the remaining crystals are collected by filtration to give (1E,3E)-1-methyl-1-(3,5-dimethoxyphenyl)-2-methoxycarbonyl-3-carboxy-4-phenylbutadiene (the same compound as the compound of Example 135) (117 g). The mother liquor (the filtrate) is concentrated, and ethyl acetate (700 ml) is added to the residue, and the (1Z,3E)-isomer is inoculated thereto. The mixture is stirred, and the precipitated crystals are collected to give (1Z,3E)-1-methyl-1-(3,5-dimethoxyphenyl)-2-methoxycarbonyl-3-carboxy-4-phenylbutadiene (the same compound as the compound of Example 121) (192 g).

Provenance & Evidence