合成路线1

In an alternative procedure, Diels-Alder condensation between methyl (E)-3-nitroacrylate (I) and cyclopentadiene (II) produces a mixture of bicyclic adducts (III) and (IV) in a 6:1 ratio. After chromatographic isolation of the major isomer (III), catalytic hydrogenation of its olefin double bond in the presence of PtO2 yields nitro ester (V). Subsequent nitro group reduction in (V) by transfer hydrogenation with ammonium formate and Pd/C produces the racemic amino ester (VI). Coupling of racemic (VI) with carboxylic acid (VII) leads to a mixture of diastereoisomeric amides (VIII) and (IX). Finally, after alkaline hydrolysis of its methyl ester function, the target carboxylic acid isomer is isolated by flash chromatography.