1) The optical resolution of pipecolic acid (I) with (+)-tartaric acid in water-ethanol gives L-pipecolic acid (II), which by reaction with Cl5P in acetyl chloride is converted to the acyl chloride (III). The condensation of (III) with 2,6-xylidine (IV) by means of N-methylpyrrolidone (NMP) in acetone affords L-pipecolic acid 2,6-xylidide (V), which is finally alkylated with propyl bromide (VI) and K2CO3 in hot isopropanol.
2) The protection of L-pipecolic acid (II) with benzyl chloroformate (VII) gives the benzyloxycarbonyl compound (VIII), which is condensed with o-toluidine (IX) by means of SOCl2 and dimethylaminopyridine (DMAP) yielding the amide (X). The methylation of (X) with methyl iodide and palladium diacetate in acetic acid affords the 2,6-xylidide (XI), which is deprotected with HBr in acetic acid to give L-pipecolic acid 2,6-xylidide (V). Finally, this compound is alkylated with propyl iodide and K2CO3 in acetonitrile.
3) The protection of 1,2,3,6-tetrahydropyridine-2(S)-carboxylic acid (XII) with benzyl chloroformate (VII) gives the benzyloxycarbonyl derivative (XIII), which is condensed with 2,6-xylidine (IV) with SOCl2 and DMAP as before yielding the amide (XIV). Deprotection of (XIV) with iodotrimethylsilane in dichloromethane affords N-(2,6-dimethylphenyl)-1,2,3,6-tetrahydropyridine-2(S)-carboxamide (XV), which is reduced with H2 over Rh/Al2O3 in DMF giving the saturated amide (V). Finally, this compound is alkylated with propyl iodide and K2CO3 as before.