Esterification of 9-fluorenylmethyloxycarbonyl α-amino acid N-carboxyanhydrides to hydroxyl-functionalized resins☆

Abstract Two hydroxyl-containing resins (Wang and Rink resins) were esterified using 9-fluorenylmethyloxycarbonyl α-amino acid N -carboxyanhydrides (Fmoc-NCAs) efficiently with high levels of substitution. The solvent of choice for this procedure was toluene. With varying amounts of N -methylmorpholine (NMM) as the base and reaction time, the level of racemization was remarkably low. For maximum substitution efficiency and low racemization, the following conditions gave the best results: toluene 15 min and NMM (1.0 equiv.) for the Wang resin and toluene 1.5 h and NMM (1.0 equiv.) for the Rink resin.