Benzylamine → N,N'-Dicyclohexylurea

Participants

Reaction Steps

Fmoc-arginine(PMC)—OH AA3 (3.83 g, 5.0 mmol) and HOBT (0.76 g, 5.0 mmol) were combined in acetonitrile (100 mL) and benzylamine (0.54 g, 5.0 mmol) was added dropwise at about rt, followed by DCC (2.06 g, 10.0 mmol) and stirred for about 16 h. A solid was filtered and the filtrate was evaporated in vacuo to an oil, which was then dissolved in ethyl acetate (100 mL) and washed with saturated NaHCO3 (2×), brine (2×), then dried (Na2SO4) and evaporated in vacuo to a solid, which was triturated with hexane (2×) to give a solid (impure with dicyclohexylurea). A portion of this solid (1.17 g, 1.25 mmol) was dissolved in acetonitrile (30 mL), diethyl amine (1.5 mL) was added and the reaction was stirred at about rt for about 1 h. The solution was then evaporated in vacuo to a solid, which was triturated with hexane (2×). The solution was then evaporated in vacuo to a solid, which was then combined in ACN (25 mL) with Fmoc-3,4-difluorophenylalanine (0.53 g, 1.25 mmol) and HOBT (0.19 g, 1.25 mmol). DIC (0.32 g, 2.5 mmol) was added and the reaction was stirred at about rt for about 16 h. Fmoc-protected dipeptide was filtered (0.77 g) and stirred in ACN (30 mL) with diethyl amine (1.5 mL) for about 2.5 h. The reaction was evaporated in vacuo to an oil, which was triturated with hexane (3×) to the white solid AA4.

Provenance & Evidence