合成路线1

3-Cyanobenzoic acid (Ia) is condensed with NH2OH in t-BuOH to yield oxime (IIa). Without isolation, compound (IIa) couples with 2-fluorobenzoyl chloride (III) in the presence of triethylamine to give oxime ester (IV), which is readily cyclized under reflux conditions (about 80 °C) (1).
Ataluren can also be obtained from its methyl ester precursor (V) by saponification with NaOH in t-BuOH/H2O (1) or THF/H2O (2) and subsequent acidification with H2SO4 (1) or HCl (2). Ataluren methyl ester (V) can be synthesized from methyl 3-cyanobenzoate (Ib) by subjecting it to either the same one-pot procedure as described above for 3-cyanobenzoic acid (Ia) (1) or, alternatively, to a similar non-one-pot procedure: condensation of (Ib) with NH2OH in EtOH at 100 ºC, coupling of the resulting oxime (IIb) with 2-fluorobenzoyl chloride (III) by means of DIEA in THF, and final cyclization of the isolated oxime ester (IVb) in toluene at 130 ºC (2). Methyl 3-cyanobenzoate (Ib) is prepared from the carboxylic acid (Ia) by methylation with CH3I in the presence of K2CO3 (2). Scheme 1.