合成路线1

4-(2-Isopropoxyethoxy)benzoic acid (VI) was activated as the corresponding imidiazolide and then condensed with magnesium monoethylmalonate to furnish, after decarboxylation, ketoester (VII). Potassium tert-butoxide-catalyzed Michael addition to (VII) of nitrostyrene (VIII) yielded adduct (IX) as a mixture of diastereoisomers. Hydrogenation of the nitro group of (IX) and further hydrogenation of the intermediate cyclic iminium trifluoroacetate salt provided the racemic cis,cis--pyrrolidine (X) as the major isomer. This was epimerized with DBU to the desired trans,trans-isomer (XI). After conversion of (XI) to the tert-butyl carbamate, resolution was carried out by chiral HPLC separation. The required (2R,3R,4S)-isomer (XII) was deprotected with trifluoroacetic acid and condensed with bromoacetamide (V) to furnish (XIII). The ethyl ester group of (XIII) was hydrolyzed with NaOH, and the title compound was finally converted to the trifluoroacetate salt.