Highly efficient condensation of sterically hindered amino acid fmoc-arg(Pbf)-OH and rink amide-AM resin

The coupling reactions of Fmoc-Arg(Pbf)-OH and Rink Amide-AM Resin with symmetrical anhydride method, active ester method and 2, 6-dichlorobenoyl chloride (DCB) method, respectively, were investigated in a self-designed reactor which congregated the stirring, filtration, and bubbling function together. The effects of reaction strategy, solvent system, reaction time, molar ratio of reactants and stirring method on the yield of condensation reaction were performed. The results indicate that the DIC/HOBt/DMAP strategy is the best method. The optimal reaction conditions are shown as follows: 3:1 of molar ratio of the reactants, 3 h of reaction time and DMA/DCM (1:1, V/V) as a solvent using nitrogen-assisted magnetic stir system. The highest yield of the condensation reaction is 93%.