Herein, we describe a one‐pot synthesis, in a mixture of water/acetonitrile, of nucleoside 5′‐polyphosphates and some derivatives starting from their corresponding nucleoside 5′‐monophosphates. Phosphorimidazolide intermediates are formed in the presence of imidazole and 2‐chloro‐1,3‐dimethylimidazolinium hexafluorophosphate. Under these mild conditions, nucleoside 5′‐di‐ and 5′‐triphosphates, dinucleoside 5′,5′‐polyphosphates, as well as some nucleotide analogues modified either on the nucleoside or on the phosphate moieties are obtained in moderate to high yields.