合成路线1

The esterification of L-phenylglycine (I) with AcCl and methanol gives the methyl ester (II), which is N-protected by means of Boc2O and TEA to yield the N-Boc derivative (III). The reduction of (III) with NaBH4 in ethanol/THF affords the alcohol (IV), which is oxidized by means of (COCl)2 and DMSO to provide the carbaldehyde (V). The reaction of (V) with vinylmagnesium bromide (VI) in THF gives the allyl alcohol (VII), which is protected with Tbdms-Cl and imidazole to yield the silyl ether (VIII). The alkylation of (VIII) with allyl bromide (IX) and NaH in DMF affords the N-allyl derivative (X), which is desilylated by means of TBAF and AcOH in THF to provide the allyl alcohol (XI). The ring closing metathesis reaction of (XI) with a Grubbs' catalyst in dichloromethane gives the tetrahydropyridine (XII), which is treated with H2 over Pd/C in ethanol to yield the chiral protected piperidine (XIII). The condensation of (XIII) with 3,5-bis(trifluoromethyl)benzyl bromide (XIV) by means of NaH in DMF affords the benzyl ether (XV), which is finally deprotected with TFA to provide the target piperidine.