After evaporation of the solvent, the residue was extracted with ethyl acetate, washed with water, and dried over sodium sulfate. After evaporation of the solvent, a white powder of N-(t-butoxycarbonyl)-L-phenylalanine 4-cis/trans-methylcyclohexylamide (I) (0.5 g) was obtained. After confirmation by NMR and IR, 4N hydrogen chloride/1,4-dioxane solution (5 ml) was added to the above compound (I) (0.5 g) under ice-cooling, and the mixture was stirred at room temperature for 30 minutes. Hexane (20 ml) was added and the solids precipitated were washed several times with diethyl ether to obtain white solids (0.45 g) of L-phenylalanine 4-cis/trans-methylcyclohexylamide hydrochloride (II). This structure was confirmed by NMR spectrum. To the mixture of 4-guanidino benzoic acid hydrochloride, dry pyridine (3 ml) and 1,3-dicyclohexylcarbodiimide (0.36 g), the above compound (II) was added under ice-cooling, and the mixture was left to stand at room temperature for 12 hours. After a conventional post-treatment, pale yellow solids of N-(4-guanidinobenzoyl)-L-phenylalanine 4-cis/trans-methylcyclohexylamide (III) (0.5 g) were obtained. After confirmation by NMR, the above compound (III) (0.5 g) was added to a saturated sodium hydrogen carbonate solution (10 ml) and the mixture was stirred for 5 minutes, followed by a recovery of the precipitates. After washing several times with water, pale yellow solids of N-(4-guanidinobenzoyl)-L-phenylalanine 4-cis/trans-methylcyclohexylamide carbonate (IV) (0.25 g). After confirmation by IR, the above compound (IV) (0.2 g) was added to a 4N hydrogen chloride/1,4-dioxane solution (1 ml) under ice-cooling, and the mixture was stirred for 20 minutes. Diethyl ether was then added, and the precipitated solids were washed several times with diethyl ether to obtain N-(4-guanidinobenzoyl)-L-phenylalanine 4-cis/transmethylcyclohexylamide hydrochloride (0.15 g) as pale yellow solids.
