Improved method for the synthesis of Nα‐9‐fluorenylmethyloxycarbonyl‐Nδ,ω bis‐adamantyloxycarbonyl‐L‐arginine

A modified method is reported for the prepartion of Nα‐9‐fluorenylmethyloxycarbonyl‐Nδ,ω bis‐adamantyloxycarbonyl‐L‐arginine, giving an overall yield of 60% over three steps based on Nα‐benzyloxycarbonyl‐L‐arginine. Commercially available adamantyl fluoroformate for guanidine function protection of Nα benzyloxycarbonyl‐L‐arginine, catalytic transfer hydrogenation with formic acid on palladium black for removal of the benzyloxycarbonyl protecting group, and fluorenylmethylsuccinimidyl carbonate for the final synthesis, were introduced to simplify and reduce the cost of preparation of this arginine derivative. The reaction conditions have been accurately studied at each step in order to optimize the yields.