Sulfuric Acid → N-(5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide

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Reaction Steps

To a mixture of N-(1-acetyl-5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide obtained in Example 9 (3.5 g) and ethanol (35 ml) was added dropwise sodium ethoxide (20 wt % ethanol solution) while keeping the reaction temperature below 30° C., and the resulting mixture was refluxed for 1 hour. After cooling to 0–5° C., concentrated sulfuric acid (6.88 g, 7.5 equivalent) was added dropwise with stirring under cooling condition while keeping the reaction temperature below 30° C., and the resulting mixture was refluxed for 2 hours. Water (17.5 ml) was added to the reaction mixture, and ethanol was evaporated off in vacuo. To the residue obtained was added ethyl acetate (35 ml), and pH of the resulting mixture was adjusted with 25% aqueous sodium hydroxide solution (the aqueous layer was adjusted to pH 12–13), and the resulting mixture was partitioned between ethyl acetate and water. The separated organic layer was furthermore washed with water (35 ml). The washing and the aqueous layer separated above were combined and reextracted with ethyl acetate (35 ml). The extract and the organic layer separated above were combined and concentrated under reduced pressure to afford the title compound (3.26 g) as a crude product.

Provenance & Evidence