合成路线1

The decarboxylation of 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylic acid ethyl ester (I) with KOH in refluxing isopropanol gives the piperidine (II), which is condensed with 3-(4-fluorophenoxy)propyl chloride (III) by means of K2CO3 in refluxing methyl isobutyl ketone to afford the alkylated piperidine (IV). The esterification of the OH group of (IV) with benzoyl chloride (V) and DMAP in dichloromethane provides the ester (VI), which is treated with sulfuric acid in dichloromethane to obtain the piperidinone (VII). The rearrangement of (VII) by means of ammonium acetate and acetic acid provides the amide (VIII), which is treated with TFA in dichloromethane to give the oxo amide (IX). The regioselective hydrogenation of the oxo group of (IX) with potassium selectride in THF affords the cis-hydroxyamide (X), which is hydrogenated with H2 over Pd/C in acetic acid to provide the 4-aminobenzamide (XI). Finally, the free OH group of (XI) is methylated with NaH and dimethyl sulfate in THF.