3-Fluoro-2-quinolones from anilines

N-(Fluoro-3-methoxyacryloyl)anilines [2-fluoro-3-methoxyprop-2-enanilides] can be prepared by condensation between lithium anilides and methyl 2-fluoro-3-methoxyprop-2-enoate. Under strongly acidic conditions, these intermediate undergo a cyclization reaction accompanied by elimination of methanol to afford 3-fluoro-2-quinolones. Substituents occupying the para or ortho position of the aniline appear at the heterocyclic 6- and 8-positions, respectively. In general, substituents attached to the mete position of the aniline lead to 1 : 1 mixtures of regioisomers. Only m-anisidine [3-methoxy-aniline] and m-fluoroaniline make an exception : they produce mainly the 7- and only trace amounts of the 5-substituted quinolone.