Sequential usage of azide and MTBD, which generates pure [18F]fluoromethyl tosylate and scavenges unreacted desmethyl precursors, provided an efficient HPLC-free strategy for the radiosynthesis of 18F-fluoromethylated compounds with high radiochemical yields and purity. This in situ18F-fluoromethylation can serve as a facile and efficient tool for the development of radiopharmaceuticals.