Hydrochloric Acid → Ethyl 2-carboethoxy-2-methyl-4-heptynoate

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Reaction Steps

Under argon atmosphere a solution of diethyl methylmalonate (20.0 g, 0.114 mol) in anhydrous THF (20 ml) was added dropwise into a stirred solution of sodium hydride (60% mineral oil dispersion, 4.6 g, 0.114 mol) in anhydrous THF (200 ml) over one hour at room temperature. A solution of 1-bromo-2-pentyne (14.0 g, 0.095 mol) in anhydrous THF (15 ml) was then added dropwise over 20 min. at room temperature. To the resulting mixture was added water (30 ml), and the mixture was neutralized with 3N hydrochloric acid, and concentrated. The residue was extracted with ethyl acetate (200 ml×2). The combined ethyl acetate layers were washed with water (50 ml) and with brine (30 ml), dried over anhydrous sodium sulfate, and concentrated to give a crude material of ethyl 2-carboethoxy-2-methyl-4-heptynoate (26.0 g). To a stirred solution of the crude material in ethanol (200 ml) was added 0.994N aqueous NaOH solution (169 ml, 0.168 mol) under ice-cooling and the mixture was stirred for 14 hrs. at room temperature. After dilution with water (30 ml), the resulting mixture was concentrated, neutralized with 6N hydrochloric acid under ice-cooling and extracted with ethyl acetate (100 ml×3). The combined ethyl acetate layers were washed with brine (50 ml), dried over anhydrous sodium sulfate, and concentrated to give a crude material of 2-carboethoxy-2-methyl-4-heptynoic acid (22.1 g). The crude material was heated at 180° C. for 2 hrs., cooled and dissolved in 100 ml of ether. A solution of diazomethane in ether was added to the solution excessively. The resulting mixture was concentrated and distilled in vacuo to give ethyl 2-methyl-4-heptynoate (12.21 g, 0.073 mol, 76%, B.p.: 118°-125° C./56 mmHg) containing methyl 2-methyl-4-heptynoate in an amount of 10% by weight.

Provenance & Evidence