4-Methylmorpholine → (2-{2-(3,5-Dimethylphenyl)-5-[1-(methoxymethylcarbamoyl)-1-methyl-ethyl]-1H-indol-3-yl}ethyl)carbamic acid tert-butyl ester

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Reaction Steps

To a suspension of 2-[3-(2-tert-butoxycarbonylamino-ethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropionic acid (1.23 g in 15 mL N,N-dimethylformamide) at 0° C. was added 608 mg of 1-hydroxybenzotriazole (HOBt), 0.48 mL 4-methylmorpholine and 352 mg of N,O-dimethylhydroxylamine hydrochlorideand the mixture stirred at low temperature. After 15 minutes, 826 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) were added and the mixture warmed to room temperature. The reaction was quenched after 3.5 days by concentration in vacuo, resuspending in ethyl acetate and washing sequentially with water, 0.3N sodium bisulfate, water, saturated sodium bicarbonate and brine. The organic portion was dried over sodium sulfate and the concentrate purified by flash chromatography on silica gel (hexane:ethyl acetate, 3:1) to give the title compound (905 mg).

Provenance & Evidence