Triethylamine → N-benzyloxycarbonyl-L-leucyl-L-phenylalanine methyl ester

Participants

Reaction Steps

To a mixture of N-benzyloxycarbonyl-L-leucine (2.7 g, 10.2 mmol), L-phenylalanine methyl ester hydrochloride (2.2 g, 10.2 mmol), and triethylamine (1.4 mL, 10.2 mmol) in dry THF (150 mL) was added N-ethyl-N'-dimethylaminopropyl-carbodiimide (EDCI) (2.2 g, 11.2 mmol) with stirring at room temperature. After the mixture was stirred overnight at room temperature, it was rotary evaporated. The residue was mixed with ethyl acetate and then washed successively with water, 1N HCl, and brine; the solution was dried (MgSO4) and evaporated to give a white solid residue. Recrystallization (EtOAc-hexane) gave 2.9 g (66%) of N-benzyloxycarbonyl-L-leucyl-L-phenylalanine methyl ester, m.p. 91°-93° C. A mixture of this ester (2.8 g, 6.6 mmol) in 2:1 dioxane-water (150 mL) was treated at 0° C. with 1N NaOH solution (7.3 mmol). After stirring the solution for 2-3 hours at room temperature, it was acidified at 0° C. by the addition of 1N HCl, and then rotary evaporated. The residue was mixed with ethyl acetate and then washed successively with water, 1N HCl, and brine; the solution was dried (MgSO4) and evaporated to give 2.7 g of N-benzyloxycarbonyl-L-leucyl-L-phenylalanine as a white solid, m.p. 120°-122° C.

Provenance & Evidence