合成路线1

The condensation of dimethyl succinate (I) with benzaldehyde (II) by means of NaOMe in refluxing methanol followed by hydrolysis with NaOH in methanol/water gives 2-benzylidenesuccinic acid (III). Compound (III) is treated with refluxing Ac2O, yielding the corresponding anhydride (IV), which by reaction with cis-perhydroisoindole (V) in toluene affords the monoamide (VI). This amide is reduced with H2 over a chiral Rhodium catalyst and treated with (R)-1-phenylethylamine (VII) to provide the chiral salt (VIII) as a single diastereomer isolated by crystallization. Finally, this salt is treated first with aqueous NH4OH and then with aqueous CaCl2.