OBJECTIVE To synthesize 5-fluorouracil derivatives containing 2-5 carbon alkanoic acid. METHODS N1-substituted derivatives containing alkanoic acid were prepared through the hydrolysis of these products of the reaction of haloesters and excessive amount of 5-fluorouracil. 5-fluorouracil were protected with tertbutoxycarbonyl (Boc) at N1-position, then reacted with haloesters and deprotected in turn, through this "one-pot" method, N3-substituted 5-FU alkanoic acid esters can be obtained, with high yields (75%-85%). The hydrolysis of these products gave N3-substituted 5-FU alkanoic acid at last. RESULTS Including 10 new compounds and 8 aim compounds, 16 derivatives of 5-fluorouracil were obtained and confirmed by the spectral detection. CONCLUSIONS The reaction of excessive amount of 5-fluorouracil and haloesters can produce a good yield of N1-substituted derivatives. N3-substituted derivatives can be obtained through the reactions of 5-fluorouracil protected with Boc at N1-position and haloesters.