合成路线1

The reaction of benzaldehyde (I) with the sulfoxide (II) by means of benzyltrimethylammonium hydroxide in methanol gives the styrene derivative (III), which is hydrolyzed with HCl in methanol to the phenylacetate (IV). The condensation of (IV) with dimethyl oxalate by means of NaH in THF yields the succinate (V), which by reaction with formaldehyde and K2CO3 is converted into the acrylate (VI). The condensation of (VI) with ethyl 3-(methylamino)propionate gives intermediate (VII), which is cyclized by means of NaH in refluxing toluene yielding the piperidinone (IX). The condensation of (IX) with trimethyl phosphonoacetate (X) by means of NaH in THF affords the expected piperidinyleneacetate (XI), which is reduced with H2 over Pd/C in methanol giving the piperidinylacetate (XII). The cyclization of (XII) by means of polyphosphoric acid (PPA) in refluxing toluene yields the benzoisoquinoline (XIII), which is finally selectively demethylated with BBr3 in methylene chloride to the target compound.