合成路线1

The reaction of 4-amino-5-chloro-2-methoxybenzoic acid (I) with benzyl chloride (II) and NaHCO3 in refluxing water gives the N-benzyl protected compound (III), which is condensed with cis-4-amino-3-methoxypiperidine-1-carboxylic acid ethyl ester (IV) by means of methyl chloroformate and TEA in dichloromethane to yield the benzamide (V). The deprotection of (V) with KOH in refluxing isopropanol affords compound (VI) with a free piperidinic NH group that is acylated with 3-(4-fluorophenoxy)propyl chloride (VII) by means of Na2CO3 in refluxing methylisobutylketone to provide the protected adduct (VIII). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in hot methanol to give the target compound. Alternatively, the piperidine derivative (VI) is treated with p-toluenesulfonic acid in refluxing toluene and then debenzylated and simultaneously reductocondensed with 3-(4-fluorophenoxy)propionaldehyde (IX) by means of H2 over Pd/C in methanol to give the target compound.