Ammonium Chloride → 2-[1-(6-Tert-butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid diethyl ester

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Reaction Steps

To a stirred solution of copper cyanide (3.58 g, 40 mmol) in tetrahydrofurane (50 mL) at −15° C. a solution of isopropylmagnesium bromide (40 mL, 2 M, 80 mmol) in tetrahydrofurane was added under argon over 15 min. After additional 15 min stirring a solution of 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethylene)-malonic acid diethyl ester (3.78 g, 10.4 mmol) in tetrahydrofurane (50 ml) was added dropwise over 15 min. After stirring for 16 h the mixture was allowed to warm up to room temperature. Then a solution of ammonium chloride (5%) in aqueous ammonia solution (5%) was added with vigorous stirring, allowing access of air. The mixture was extracted twice with ethyl acetate. The combined organic layers were washed successively with aqueous ammonia solution (5%) and brine, and dried over magnesium sulphate. The solvent was removed under reduced pressure and the residue was purified by column chromatography (silica gel, 1.7% methanol in dichloromethane) to give crude 2-[1-(6-tert-butoxycarbonylamino-pyridin-3-yl)-2-methyl-propyl]-malonic acid diethyl ester (2.85 g, 25%).

Provenance & Evidence