Triethylamine → {(1R)-1-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl}-2-(2-naphthyl)ethyl}carbamic acid tertbutyl ester

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Reaction Steps

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.3 g, 32.9 mmol) and 1-hydroxybenzotriazole monohydrate (5.0 g, 32.9 mmol) were added to a solution of (R) N-tert-butoxycarbonyl-3-(2-naphthyl)-alanine (10.4 g, 32.9 mmol) in N,N-dimethylformamide (140 ml). After 1 h at 20° C. a mixture of 1-(3-methyl-[1,2,4]oxadiazole-5-yl)-2-phenylethylamine hydrochloride (5.6 g, 23.5 mmol) and triethylamine (2.37 g, 23.5 mmol) in N,N-dimethylformamide (100 ml) were added. After 18 h at 20° C. the reaction mixture was poured onto water (1.4 L) and extracted several times with ethyl acetate (total 1.4 L). The combined organic phases were washed with aqueous citric acid (10%, 200 ml), a saturated solution of sodium hydrogencarbonate (200 ml) and water (3×200 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo and crystallized from ethyl acetate and heptane to give 9.45 g of {(1R)-1-{(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-phenylethylcarbamoyl}-2-(2-naphthyl)ethyl}carbamic acid tertbutyl ester.

Provenance & Evidence