The reductocondensation of 4-benzyloxyaniline (I) with 1-(tert-butoxycarbonyl)piperidin-4-one (II) by means of NaBH(OAc)2 in dichloromethane gives N-(4-benzyloxyphenyl)-N-[1-(tert-butoxycarbonyl)piperidin-4-yl]amine (III), which is alkylated with 3-methyl-2-butenyl bromide (IV) by means of DIEA in THF yielding the tertiary amine (V). The deprotection of (V) with TFA in dichloromethane affords the piperidine (VI), which is condensed with N-(tert-butoxycarbonyl)-L-leucine (VII) by means of HBTU and DIEA in DMF to provide the intermediate (VIII). Finally, (VIII) is deprotected with TFA in dichloromethane.
The reaction of N-(tert-butoxycarbonyl)-L-leucine (I) with N,O-dimethylhydroxylamine and HBTU in DMF gives the corresponding methoxyamide (II), which is reduced with LiAlH4 in ethyl ether yielding the aldehyde (III). The reductocondensation of (III) with the piperidine (IV) by means of sodium triacetoxyborohydride in dichloromethane affords the protected adduct (V), which is finally deprotected with TFA in dichloromethane. The intermediate piperidine (IV) has been obtained as follows: The reductocondensation of the piperidinone (VI) with 4-(benzyloxy)aniline (VII) by means of sodium triacetoxyborohydride in dichloromethane gives the secondary amine (VIII), which is alkylated with 3-methyl-2-butenyl bromide (IX) and DIPEA in THF yielding the protected piperidine (IX). Finally, this compound is deprotected with TFA in dichloromethane to afford the target intermediate (IV).