[reaction: see text] 2'-C-beta-Fluoromethyluridine (17) represents both a potentially important biological agent and a tool for biochemical analysis. Here we describe the first synthesis of this compound starting from uridine. The key steps include protection of the uracil base with methoxyethoxymethyl (MEM) chloride, conversion to the corresponding 2'-C-alpha-epoxide, and regioselective opening of the oxirane ring with potassium fluoride/hydrogen fluoride. Subsequent acetylation of the 3'- and 5'-hydroxyl groups enables MEM removal using B-bromocatecholborane. Deacetylation generates the parent nucleoside, 2'-C-beta-flurormethyluridine.