Diisopropylethylamine → ((3-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl)phenyl)methyl)carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

3-(tert-Butoxycarbonylaminomethyl)benzoic acid (113 mg, 0.45 mmol) and 7-aza-1-hydroxybenzotriazole (61 mg, 0.45 mmol) were dissolved in N,N-dimethylformamide (1 ml) and dichloromethane (1 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (86 mg, 0.45 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of (2R)-2-amino-N-{2-[2-(2-hydroxyethoxy)phenyl]ethyl}-N-methyl-3-(2-naphthyl)propionamide (175 mg, 0.45 mmol) and ethyldiisopropylamine (0.08 ml, 0.45 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (50 ml) and washed with a 10% aqueous solution of sodium hydrogen sulfate (50 ml). The aqueous phase was extracted with ethyl acetate (2×15 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (40 g), using ethyl acetate/heptane 3:1 as eluent, to give 211 mg of ((3-((1R)-1-(N-(2-(2-(2-hydroxyethoxy)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethylcarbamoyl)phenyl)methyl)carbamic acid tert-butyl ester.

Provenance & Evidence