合成路线1

Intramolecular cyclization of N-(2-benzylphenyl)formamide (I) in the presence of phosphoric acid and phosphoryl chloride affords dibenzoazepine (II). Subsequent catalytic hydrogenation of (II) over Pd/C gives rise to the dihydro derivative (III). Alternatively, the tricyclic compound (III) has been obtained by ring closure of 2-(benzylamino)benzyl alcohol (IV) under acidic conditions. Oxidation of (III) employing either the Davis reagent (3-phenyl-2-(phenylsulfonyl)oxaziridine) or m-chloroperbenzoic acid furnishes nitrone (V). The cycloaddition of nitrone (V) with N,N-dimethyl allylamine (VI) gives rise to the isoxazolidine adduct (VII) as a mixture of diastereoisomers. Separation of the racemic cis/trans-isomers by silica gel column chromatography, followed by separation of the enantiomers on a chiral solid phase, provides the target (R,R)-enantiomer, which is finally isolated as the corresponding L-malate salt.