Hydrochloric Acid → N-(2,6-Diisopropyl-phenyl)-malonamic acid

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Reaction Steps

A 5 L 4-necked flask was fitted with a mechanical stirrer and charged with 240.24 g (824 mmol) of the N-(2,6-Diisopropyl-phenyl)-malonamic acid ethyl ester produced immediately above and 1200 mL of methanol. To the clear, orange solution was added 483 mL (966 mmol) of 2.0 N sodium hydroxide. The solution was stirred until HPLC analysis indicated complete reaction (ca. 2.5 h) and then acidified to pH 3 with 3N hydrochloric acid. The suspension was diluted with 2.0 L of ethyl acetate and 0.5 L of water. The aqueous layer was removed and then the organic layer was washed with 0.5 L of water and 0.5 L of brine. The aqueous layers were back-extracted with 0.5 L of ethyl acetate and the combined organic layers were then dried over magnesium sulfate. Evaporation of the solvent at the Rotavap yielded 216 g (99%) of the crude acid as yellowish solids. The crude material was slurried with 2.2 L of heptane and then isolated by filtration. The solids were washed with heptane and petroleum ether and then air-dried giving 202.53 g of the N-(2,6-Diisopropyl-phenyl)-malonamic acid as yellowish solids. HPLC analysis indicated >99% (a/a) purity. The materials 1H-NMR spectrum was consistent with structure.

Provenance & Evidence