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Abstract
1-[((S)-2-Hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine (cyc-lic HPMPC) was readily synthesized in gram to multi-kilogram quantities by treating a DMF suspension of HPMPC with four molar equivalents of ethyl chloroformate. This dehydrative intramolecular cyclization process typically afforded cHPMPC in 94% isolated yield and high purity. Benign by-products and solvents were easily removed.