Triethylamine → t-butyloxycarbonyl-4-hydroxy-L-phenylalanine cyclohexylamide

Participants

Reaction Steps

N-(t-butyloxycarbonyl)-4-nitro-D,L-phenylalanine (0.95 g) and triethylamine (0.4 ml) were dissolved in dry tetrahydrofuran (15 ml), and ethylchorocarbonate (0.33 g) was added under ice-cooling to the resultant solution, followed by stirring for 20 minutes. 4-benzoylaniline (0.6 g) was added to the solution and the mixture was further stirred at room temperature for 12 hours. According to a conventional post-treatment, 0.98 g of N-(t-butyloxycarbonyl)-4-nitro-D,L-phenylalanine 4-benzoylanilide (I) was obtained. To the above compound (I) (0.37 g) was added 4N-hydrogen chloride/dioxane solution (1.5 ml) and the mixture was stirred at room temperature for 1 hour. The solid precipitated by addition of ethyl ether (10 ml) into this solution was collected by filtration to give 0.33 g of 4-nitro-D,L-phenylalanine 4-benzoylanilide hydrochloride (II). Trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarboxylic acid (0.2 g) and triethylamine (0.2 ml) were dissolved in dry tetrahydrofuran (15 ml) and ethyl chlorocarbonate (0.09 g) was added to the solution under ice-cooling, followed by stirring for 20 minutes. To this solution was added the above compound (II) (0.33 g) and the mixture as stirred at room temperature for 12 hours. According to a conventional post-treatment, 0.29 g of N-[trans-4-(t-butyloxycarbonyl)aminomethylcyclohexylcarbonyl]-4-nitro-D,L-phenylalanine 4-benzoylanilide (III) was obtained. The above compound (III) (0.29 g) was dissolved in 4N-hydrogen chloride/dioxane solution (1 ml), the solution was stirred at room temperature for 1 hour and then ether (8 ml) was added. The crystalline substance precipitated was collected by filtration and subjected to a conventional post-treatment, whereby 0.24 g of N-(trans-4-aminomethylcyclohexylcarbonyl)-4-nitro-D,L-phenylalanine 4-benzoylanilide hydrochloride was obtained.

Provenance & Evidence