A new series of 2-substituted-6-fluoro-5-(4-methyl-1-piperazinyl)benzoxazoles 48 (a-c) were prepared for screening against solid tumor cell lines. The reaction of 4 fluoro-5-(4-methyl-1-piperazinyl)-2-nitrophenol (47) with orthoesters at refluxing conditions lead to the desired benzoxazoles in good yields. The key intermediate in this synthesis was prepared starting from 3-chloro-4-fluorophenol (45) in two steps, nitration and piperazinylation. The structures of the synthesized compounds and intermediates were established from IR, 'H and 13C NMR and mass spectrometry spectral data.