Nucleosides and Nucleotides. Part 17. A simple preparation of protected deoxynucleoside‐3'‐phosphates

A simple method for the preparation of fully protected 2′‐deoxynucleoside‐3′‐phosphates is described. The main step, phosphorylation of partially protected deoxynucleosides, is performed with the monofunctional reagent p ‐chlorophenyl (2‐cyanoethyl) phosphochloridate 3 ) ( 2 ) in dioxane. This reagent is quickly prepared from readily accessible p ‐chlorophenyl phosphodichloridate by reaction with 3‐hydroxypropionitrile and triethylamine in dioxane or ether. The crude reagent is used directly for phosphorylation. After chromatography, protected deoxynucleoside‐3′‐phosphates were isolated in yields of 80–87%. The method described here, which has been optimized in detail, represents a simple alternative to published methods.