合成路线1

Acylation of 4-benzyl-4-hydroxypiperidine (I) by means of benzyl chloroformate provides carbamate (II). Subsequent dehydration of the tertiary alcohol group of (II) employing SOCl2 and pyridine leads to the tetrahydropyridine (III). Oxidation of tetrahydropyridine (III) with m-chloroperbenzoic acid gives epoxide (IV) which, upon acidic hydrolysis, is converted to the trans-diol (V). Resolution of the racemic diol (V) is performed via esterification with (S)-N-trifluoroacetylproline chloride (VI), followed by chromatographic separation of the resultant diastereomeric esters. The desired isomer (VII) is then hydrolyzed under basic conditions to yield the (R,R)-diol (VIII). Removal of the N-carbobenzoxy group of (VIII) by hydrogenolysis leads to (R,R)-4-benzyl-3,4-dihydroxypiperidine (IX), which is alkylated by the alkyl chloride (X) to produce (XI). Finally, hydrogenolysis of the benzyl ether group of (XI) furnishes the title compound.