合成路线1

The hydrolysis of 1-benzyl-4-(methylamino)piperidine-4-carboxamide (I) with refluxing concentrated aqueous HCl gives the corresponding free acid (II), which is debenzylated with H2 over Pd/C in basic medium yielding 4-(methylamino)piperidine-4-carboxylic acid sodium salt (III). The protection of (III) with benzyl chloroformate (IV) in basic THF - water affords 1-(benzyloxycarbonyl)-4-(methylamino)piperidine 4 carboxylic acid (V), which by cyclization with phosgene in dioxane is converted to benzyl 1-methyl-2,4-dioxo 3-oxa-1,8-diazaspiro[4.5]decane-8 carboxylate (VI). The reaction of (VI) with 2,6-dimethylaniline (II) by heating at 160 C gives benzyl 4-(2,6-dimethylphenylaminocarbonyl)-4-(methylamino)piperidine-1-carboxylate (VIII), which is methylated with refluxing methyl iodide to the corresponding dimethylamino compound (IX). The deprotection of (IX) with H2 over Pd/C in methanol yields 4-(dimethylamino)-N-(2,6-dimethylphenyl)piperidine-4-carboxamide (X), which is finally condensed with 1,2-epoxycyclohexane (XI) in refluxing ethanol.