Reductive amination of N-Boc-4-piperidone (I) with allylamine (II) in the presence of sodium triacetoxyborohydride afforded aminopiperidine (III), which was acylated with 4-nitrobenzyl chloroformate (IV) to yield carbamate (V). Removal of the Boc group of (V) by means of a methanolic solution of HCl, prepared from acetyl chloride and MeOH, provided piperidine (VI).
Reductive amination of N-Boc-4-piperidone (I) with allyl amine (II) in the presence of sodium triacetoxyborohydride gave aminopiperidine (III), which was condensed with 4-nitrobenzyl chloroformate (IV) to afford carbamate (V). The Boc group of (V) was then cleaved by treatment with methanolic HCl to produce intermediate piperidine (VI). Alternatively, the condensation of 1-Boc-piperidine-4-amine (VII) with chloroformate (IV) gives carbamate (VIII), which is allylated with allyl chloride (IX) and NaH in THF, yielding the already reported carbamate (V).
Reductive amination of 2,5-dimethyl-2-phenylhex-4-enal (X) with methylamine and NaBH3 gives the expected secondary amine as a racemic mixture that is separated by means of mandelic acid, yielding the desired isomer (XI). The sulfonylation of the resulting amine (XI) with benzenesulfonyl chloride (XII) provided sulfonamide (XIII). Dihydroxylation with N-methylmorpholine-N-oxide in the presence of a catalytic amount of osmium tetroxide gave rise to diol (XIV), which was oxidatively cleaved to aldehyde (XV) by means of sodium periodate. Finally, reductive condensation between aldehyde (XV) and piperidine (VI) furnished the title compound.