合成路线1

Alkylation of diethyl malonate (I) with chloroethyl ether (II) in the presence of NaOEt in refluxing EtOH provided tetrahydropyran dicarboxylate (III). Hydrolysis of diester (III) with ethanolic KOH, and decarboxylation of the resulting diacid (IV) at 180 C gave tetrahydropyran-4-carboxylic acid (V). This was reduced to the alcohol (VI) on treatment with LiAlH4 in refluxing THF, and then converted into mesylate (VII) by reaction with metanesulfonyl chloride and triethylamine in THF. 3-(Aminomethyl)pyridine (VIII) was protected as the imine (X) by reaction with benzophenone (IX) in refluxing benzene with a Dean-Stark trap. Alkylation of imine (X) with mesylate (VII) in the presence of LDA in cold THF gave intermediate (XI) which, on acidic hydrolysis provided amine (XII). Reaction of (XII) with saturated aqueous HBr at 100 C in a pressure tube formed dibromide (XIII), which was basified with K2CO3 and heated to 80 C to provide the target quinuclidine.