合成路线1

Knoevenagel condensation of pyridine-3-carboxaldehyde (I) with malonic acid in the presence of ammonium acetate afforded the racemic amino acid (III), which was acylated with phenylacetyl chloride (IV) to give amide (V). Optical resolution of (V) by means of penicillin amidase produced the hydrolysis of the undesired (R)-enantiomer. After isolation of the unreacted (S)-enantiomer (VI), its hydrolysis with aqueous HCl furnished the chiral amino acid (VII), which was converted to methyl ester (VIII) with 2,2-dimethoxypropane in MeOH. Coupling of (VIII) with N-Boc-(R)-nipecotic acid (IX) using 2-benzotriazolyl-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) provided amide (X). Deprotection of the Boc group of (X) was then achieved with HCl in dioxan resulting amine (XI).