合成路线1

Alkylation of methyl [1-(4-chlorobenzyl)but-3-enyl]carbamate (I) with chloromethyl ethyl ether in the presence of NaH afforded carbamate (II). Cyclization of (II) using chlorosulfonic acid in acetonitrile gave the trans-acetylamino piperidine (III). After removal of the carbamate group of (III) with HBr in HOAc, the racemic piperidine (IV) was resolved by acylation with (S)-O-acetylmandelic acid chloride (V), followed by recrystallization of the desired diastereoisomer (VI). Hydrolysis of (VI) with aqueous HCl furnished the chiral amino piperidine (VII), which was selectively protected with benzaldehyde (VIII) at the primary amino group as the corresponding benzaldimine (IX). Condensation of piperidine (IX) with 3,5-bis(trifluoromethyl)benzoyl chloride (X) followed by acid hydrolysis of the benzaldimine function produced the amino amide (XI). This was finally coupled with quinoline-4-carbonyl chloride (XII), yielding the title compound.