合成路线1

The reaction of 4-fluoro-2-nitrobenzoic acid (IX) with refluxing SOCl2 gives the corresponding acyl chloride (X), which is then condensed with alpha-acetyl-gamma-butyrolactone (XI) by means of Mg(OEt)2 in toluene yielding alpha-acetyl-alpha-(4-fluoro-2-nitrobenzoyl)-gamma-butyrolactone (XII). The hydrolysis of (XII) with HCl affords alpha-(4-fluoro-2-nitrobenzoyl)-gamma-butyrolactone (XIII), which by treatment with HBr (d, 1.48) at 85 C is converted into gamma-bromo-4-fluoro-2-nitrobutyrophenone (XIV). The ketalization of (XIV) with ethyleneglycol and ethylenesulfite by means of p-toluenesulfonic acid in refluxing toluene yields the corresponding ketal (XV), which is condensed with the piperidine (V) by means of K2CO3 in hot methyl isobutylketone giving 4-[4-hydroxy-4-(3-trifluoromethylphenyl)piperidino]-1-(4-fluoro-2-nitrophenyl)-1,1-ethylenedioxy-n-butane (XVI). The hydrolysis of (XVI) HCl in refluxing isopropanol affords gamma-[hydroxy-4-(3-trifluoromethylphenyl)piperidino]-4-fluoro-2-nitrobutyrophenone (XVII), which is finally reduced with H2 over Pd/C in MeOH The direct condensation of butyrophenone (XIV) with piperidine (V) by means of K2CO3 as before gives the already obtained butyrophenone (XVII).