Ethyl Acetate → N-(1-acetyl-5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide

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Reaction Steps

To a solution of 1-acetyl-7-amino-5-ethoxycarbonylmethyl-4,6-dimethylindoline obtained in Example 7 (4.0 g) in dichloromethane (40 ml) was added diisopropylethylamine (2.14 g, 1.2 equivalent) with stirring, and the resulting mixture was cooled to 0–5° C. Subsequently, to the reaction mixture was added dropwise pivaloyl chloride (1.74 g, 1.05 equivalent) at 0–5° C., and the resulting mixture was stirred for 1.0 hour at this temperature. The reaction mixture was washed with water (40 ml), and the resulting mixture was partitioned. The separated organic layer was washed twice with a saturated sodium hydrogen carbonate solution (20 ml each) and concentrated under reduced pressure. To the residue obtained was added ethyl acetate (20 ml), and the resulting mixture was concentrated under reduced pressure to about 12 ml. This addition and evaporation of ethyl acetate was repeated once again, and the resulting mixture was stirred at room temperature. After stirring, ethylcyclohexane (28 ml) was added, and the resulting mixture was stirred for more than 10 minutes at room temperature and then for more than 30 minutes at 0–5° C. Crystals precipitated were separated by filtration, washed with a mixed solvent of ethyl acetate and ethylcyclohexane (1:4)(40 ml) and dried under reduced pressure (50° C.) to afford the title compound (3.92 g, yield: 76%) as colourless crystals.

Provenance & Evidence