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

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.

1. additionwere added
2. additionAfter 18 h at 20° C. the reaction mixture was poured onto water (1.4 L)
3. extractionextracted several times with ethyl acetate (total 1.4 L)
4. washThe combined organic phases were washed with aqueous citric acid (10%, 200 ml)
5. dry with materialAfter drying (magnesium sulfate) the solution
6. concentrationwas concentrated in vacuo
7. customcrystallized from ethyl acetate and heptane

ORD record

ord-ed3e614c68cd45f5897fe0a8bf97633a

Source dataset

uspto-grants-2002_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06350767B1