合成路线1

Fexofenadine has been obtained by two new related ways: 1) The Grignard condensation of ethyl 2-(4-formylphenyl)-2-methylpropionate (I) with 2-(1,3-dioxolan-2-yl)ethylmagnesium bromide (II) gives the corresponding carbinol (III), which by a treatment with Amberlyst-15 yields the lactol (IV). The reductocondensation of (IV) with the piperidine derivative (V) by means of NaBH4 in methanol affords the ethyl ester (VI), which is finally hydrolyzed with NaOH. 2) The Grignard condensation of ethyl 2-[4-(chloroformyl)phenyl]-2-methylpropionate (VII) with 2-(1,3-dioxolan-2-yl)ethylmagnesium bromide (II) gives the corresponding ketone (VIII), which is reduced to carbinol (III) in the usual way. 3) The (S)-enantiomer of fexofenadine can be synthesized through the asymmetric reduction of the prochiral ketone (VIII) with chiral catalysts to afford the (S)-enantiomer of carbinol (III).