新产品编号:911741
Chemical Name: (+)-4(R)-[2-(1,1-Diphenylmethoxy)ethyl]-1-(4-fluorobenzyl)piperidin-3(R)-ol
CAS No. 383362-75-2 (stereoisomer)
项目整合开发状态: Preclinical
项目研究机构: Wayne State University (Originator)
合成路线:Alkylation of 2-pyridin-4-ylethanol (I) with 4-fluorobenzyl chloride (II),followed by reduction of the resultant pyridinium salt (III) with NaBH4 leads to the tetrahydropyridine (IV).Acid-catalyzed condensation of alcohol (IV) with benzhydrol (V) then provides the benzhydryl ether (VI) (1).Hydroboration of tetrahydropyridine (VI) and subsequent oxidative work up gives rise to the racemic trans piperidinol rac-(VII) (1,2).Resolution of (VII) is accomplished via esterification with (-)-camphanic chloride (VIII),followed by HPLC separation of the resulting diastereoisomers.The desired isomer (IX) is finally hydrolyzed employing K2CO3 in MeOH to provide the target enantiomer
📌 参考资料/链接：
参考文献标题:N- and O-substd.4-[2-(diphenylmethoxy)-ethyl]-1-[(phenyl)methyl]piperidine analogs and methods of treating CNS disorders therewith
文献作者:Dutta,A.K.(Wayne State University)
参考来源:WO 0198266
📄 详细内容
合成路线:Alkylation of 2-pyridin-4-ylethanol (I) with 4-fluorobenzyl chloride (II),followed by reduction of the resultant pyridinium salt (III) with NaBH4 leads to the tetrahydropyridine (IV).Acid-catalyzed condensation of alcohol (IV) with benzhydrol (V) then provides the benzhydryl ether (VI) (1).Hydroboration of tetrahydropyridine (VI) and subsequent oxidative work up gives rise to the racemic trans piperidinol rac-(VII) (1,2).Resolution of (VII) is accomplished via esterification with (-)-camphanic chloride (VIII),followed by HPLC separation of the resulting diastereoisomers.The desired isomer (IX) is finally hydrolyzed employing K2CO3 in MeOH to provide the target enantiomer
参考文献标题:High affinity hydroxypiperidine analogues of 4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidine for the dopamine transporter: Stereospecific interactions in vitro and in vivo
文献作者:Ghorai,S.K.; Cook,C.; Davis,M.; Venkataraman,S.K.; George,C.; Beardsley,P.M.; Reith,M.E.A.; Dutta,A.K.
参考来源:J Med Chem 2003,46(7),1220