合成路线1

The reaction of methyl 5-hydroxy-3(R)-methylpentanoate (I) with 4-methoxybenzyalmine in refluxing toluene gives the corresponding amide (II), which is cyclized by means of SO3/pyridine in DMSO/TEA to yield the 6-hydroxypiperidinone (III). The dehydration of (III) in refluxing toluene, or by means of PPA in refluxing dimethyl carbonate affords the tetrahydropyridinone (IV). The reaction of (IV) with ethyl trichloroacetate (V) by means of Na-OEt in dimethyl carbonate gives the 2-azabicyclo[4,1,0]heptane derivative (VI), which is monodechlorinated by means of Zn and ethylenediamine in refluxing methanol/water to yield a diastereomeric mixture of monochloro compounds (VII). The treatment of (VII) with Ms-OH in refluxing toluene, followed by treatment with aq. NaOH affords the desired deprotected monochloro isomer (VIII). The reaction of the ketone group of (VIII) with trimethyloxonium tetrafluoroborate in dimethyl carbonate provides the enol ether (IX), which is finally treated with ammonium acetate in refluxing ethanol to give the target imine.