Efficient synthesis of nucleoside aryloxy phosphoramidate prodrugs utilizing benzyloxycarbonyl protection

An efficient method for the synthesis of nucleoside phosphoramidates prodrugs (6a–f) has been developed that employs a simple protection/deprotection sequence of the nucleoside with benzyloxycarbonyl (Cbz). The coupling reaction of Cbz-protected derivatives (5a–f) with phenyl-(ethoxy-l-alaninyl)-phosphorochloridate (7), followed by Cbz group removal by hydrogenolysis provided the phenyl phosphoramidate ProTides (6a–f) in excellent overall yields.