Hydrochloric Acid → 3-(4-Heptylcarbamoylmethyl-phenyl)-2,2-dimethyl-propionic acid ethyl ester

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Reaction Steps

To a stirred solution of 3-(4-carboxymethyl-phenyl)-2,2-dimethyl-propionic acid ethyl ester (0.97 g, 3.67 mmol) in chloroform (15 mL) under an nitrogen atmosphere was added thionyl chloride (11 mmol, 0.804 mL). The mixture was heated under reflux for 2.75 hours, cooled to room temperature and concentrated under reduced pressure to a clear oil. The oil was dissolved in methylene chloride (0.50 mL) then added dropwise to a solution of 1-heptylamine (4.40 mmol, 0.653 mL) and N,N-diisopropylethylamine (4.40 mmol, 0.765 mL) in anhydrous dichloromethane (5 mL) cooled to 0° C. The solution was warmed to room temperature and allowed to stir for 30 minutes, then was poured over a solution of 1 M HCl (10 mL). The aqueous layer was isolated and extracted with diethyl ether (2×). The organic layers were combined, washed with 2N HCl (2×), brine (1×), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude 3-(4-heptylcarbamoylmethyl-phenyl)-2,2-dimethyl-propionic acid ethyl ester as an orange oil. The oil was used in the preparation of 3-[4-(2-heptylamino-ethyl)-phenyl]-2,2-dimethyl-propionic acid ethyl ester without further purification. (1.27 g, 95%).

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