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A practical synthesis of the antiviral agent lobucavir, [1R-(1r,2β,3r)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6Hpurin-6-one (BMS-180194), is described. The key chiral intermediate, [1S-(1r,2β,3r)]-3-hydroxy-1,2-cyclobutanedimethanol, dibenzoate ester, was made by an asymmetric [2 + 2] cycloaddition of dimenthyl fumarate with ketene dimethyl acetal followed by sequential diester reduction, benzoylation, deketalization, and stereoselective ketone reduction. Regioselective N9-alkylation of the tetra-n-butylammonium salt of 2-amino-6-iodopurine with the derived cyclobutyltriflate furnished the purinecyclobutyl dibenzoate. Methanolysis followed by acid hydrolysis produced lobucavir in a 35% overall yield with an ee > 99%.