Dicyclohexylcarbodiimide → N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanyl-N-[1-[1-hydroxy-2-(1-methylethoxy)-2-oxoethyl]-3-methylbutyl]-1-(triphenylmethyl)-L-histidinamide

Participants

Reaction Steps

To a mixture of 1.1 g (4 mmol) of N-[(1,1dimethylethoxy)carbonyl]-L-phenylalanine and 0.568 g (4.2 mmol) of 1-hydroxybenzotriazole in 5 ml of dimethylformamide at 0° C. is added 2.4 g (4.1 mmol) of 3-[[2-amino-1-oxo-3-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]amino]-2-hydroxy-5-methylhexanoic acid, 1-methylethyl ester (mixture of [2R-[2R*,3S*(S*)]] and [2S-[2R*,3R*(R*)]]-isomers) in 15 ml of dimethylformamide. The solution is stirred for five minutes, treated with 0.867 g (4.2 mmol) of dicyclohexylcarbodiimide, stirred at 0° C. for one hour, warmed to room temperature, stirred overnight, filtered and the dimethylformamide evaporated in vacuo. The resulting oil is dissolved in ethyl acetate and washed successively with 30 ml of 1N citric acid solution, 30 ml of saturated solution of sodium bicarbonate and 30 ml of saturated solution of sodium chloride. The organic layer is separated, dried (magnesium sulfate) and evaporated in vacuo to a foam. The foam is chromatographed over 250 g of silica gel (230-400 mesh), eluted with 5% methanol 95% chloroform, the combined fractions evaporated in vacuo and the residue dried under high vacuum overnight to afford 2.3 g of the title compound as a white foam.

Provenance & Evidence