3-(4-Hydroxy-3-Methoxyphenyl)Prop-2-Enoic Acid → 3-[4-(2,4-Dichlorobenzyloxy)-3-methoxyphenyl]-propionic acid

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Reaction Steps

16.6 g. of vanillin, 22.4 g. of triethylphosphonoacetate, and 5.75 g. of sodium hydride - oil suspension (80%) in 100 ml. of dimethylformamide are reacted analogously to Example 75. Reaction time: 6 hours at 100°. 21 g. of the thus-obtained ethyl ester of 3-(4-hydroxy-3-methoxyphenyl)-acrylic acid is hydrogenated as described in Example 75. 10 g. of the thus-formed ethyl ester of 3-(4-hydroxy-3-methoxyphenyl)-propionic acid is combined in 100 ml. of dimethylformamide with 1.34 g. of sodium hydride - oil suspension (80%), and after 15 minutes at room temperature, 8.8 g. of 2,4-dichlorobenzyl chloride is added thereto. After 2 hours at room temperature, the mixture is poured on 1N sulfuric acid and extracted with ethyl acetate. After drying and evaporation, 17 g. of the ethyl ester of 3-[4-(2,4-dichlorobenzyloxy)-3-methoxyphenyl]-propionic acid is obtained and slowly combined in 200 ml. ether with 7.1 g. Br in 10 ml. of carbon tetrachloride. After the bromine coloring has disappeared, the mixture is extracted with water and potassium bicarbonate solution, and the ether phase is dried and evaporated. After recrystallization from ethanol, 13.9 g. of the ethyl ester of 3-[2-bromo-4-(2,4-dichlorobenzyloxy)-5-methoxyphenyl]-propionic acid is obtained, m.p. 102°-106° By lithium aluminum hydride reduction of 10 g. of this compound in tetrahydrofuran, 7.5 g. of 3-[2-bromo-4-(2,4-dichlorobenzyloxy)-5-methoxyphenyl] -1-propanol is obtained, m.p. 102°-103°. This product is reacted analogously to Example 75 with thionyl chloride and then with sodium imidazole to obtain the final product. Yield: 2.72 g.; m.p. 142°-144° (from acetonitrile).

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