International audienceWe report on the first solution synthesis of lamivudine 5'-diphosphate in both high yield and purity. Efficient synthesis of lamivudine 5'-monophosphate was obtained through lamivudine H-phosphonate oxydation by (-)-(8,8-dichlorocamphorylsulfonyl)oxaridine. Diphosphorylation was performed by nucleophilic substitution of the phosphorimidazolate derivative of lamivudine HPLC coupled with UV or MS detection was found to be an invaluable tool for the follow-up of phosphorylation reactions