Triethylamine → 2-hydroxy-5-methyl-3-[[1-oxo-2[[(phenylmethoxy)carbonyl]amino]-3-[1-(triphenylmethyl)-1H-imidazol-4-yl]propyl]amino]hexanoic acid

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Reaction Steps

A mixture of 12.4 g (23.4 mmol) of N-[(phenylmethoxy)carbonyl]-1-(triphenylmethyl)-L-histidine, (Jones, J. H., et al, Synthesis, page 1110 (1987)) 3.3 g (24.6 mmol) of 1-hydroxybenzotriazole and 50 ml of dimethylformamide is cooled to <0° C. and treated with a mixture of 5.6 g (23.4 mmol) of (3S)-3-amino-2-hydroxy-5methylhexanoic acid, 1-methylethyl ester, monohydrochloride (mixture of isomers at hydroxy center) (Example B), and 2.5 g (25 mmol) of triethylamine in 30 ml of dimethylformamide at -5° C. The solution is stirred for five minutes, treated with 5.1 g (24.6 mmol) of dicyclohexylcarbodiimide in 30 ml of dimethylformamide and stirred for eight hours at -5 to 0° C., kept at -5° C. overnight, allowed to warm to room temperature under a nitrogen atmosphere and stirred for 24 hours. The mixture is treated with 1 g (10 mmol) of triethylamine, stirred at room temperature for 72 hours, filtered and the dimethylformamide evaporated in vacuo. The residue is dissolved in 200 ml of ethyl acetate, extracted with 200 ml of 1N citric acid solution, filtered, extracted with 200 ml of saturated sodium chloride solution, 200 ml of saturated solution of sodium bicarbonate and 200 ml of saturated solution of sodium chloride. The organic layer is separated, dried (magnesium sulfate) and the solvent evaporated in vacuo to give 14.1 g of the title compound as a tan foam.

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