Picenadol hydrochloride, LY-136595((-)-enantiomer), LY-136596((+)-enantiomer), LY-150720
哌西那朵Chemical Name: (?-trans-3-(1,3-Dimethyl-4-propyl-4-piperidinyl)phenol hydrochloride; (?-trans-m-(1,3-Dimethyl-4-propyl-4-piperidyl)phenol hydrochloride; (?-trans-1,3-Dimethyl-4-propyl-4-(3-hydroxyphenyl)piperidine hydrochloride
CAS No. 74685-16-8, 79201-85-7 (free base)
项目整合开发状态: Phase III
项目研究机构: Lilly (Originator)
合成路线:The methylation of 2-methyl-3-propyl-3-(3-methoxyphenyl)-1-pyrroline (I) with dimethyl sulfate in refluxing butanone gives 1-methyl-3-propyl-2-exo-methylene-3-(3-methoxyphenyl)pyrrolidine (II),which by reaction with HBF4 in ethanol is converted into 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)pyrrolinium tetrafluoroborate (III).The methylation of (III) with diazomethane in dichloromethane ether yields 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)-1,2-ethylenepyrrolidinium tetrafluoroborate (IV),which by heating at 180 C and neutralization with NaOH affords 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)-1,4,5,6-tetrahydropyridine (V).The reduction of (V) with NaBH4 in THF gives 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)piperidine (VI),which is finally treated with 48% HBr in refluxing acetic acid.
📌 参考资料/链接：
参考文献标题:1,3,4-Trisubstituted-4-arylpiperidines and their preparation
文献作者:Zimmerman,D.M.(Eli Lilly and Company)
参考来源:BE 0833044; DE 2539452; FR 2283679; FR 2299337; GB 1525584; JP 7648670; JP 7783572
📄 详细内容
合成路线:The methylation of 2-methyl-3-propyl-3-(3-methoxyphenyl)-1-pyrroline (I) with dimethyl sulfate in refluxing butanone gives 1-methyl-3-propyl-2-exo-methylene-3-(3-methoxyphenyl)pyrrolidine (II),which by reaction with HBF4 in ethanol is converted into 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)pyrrolinium tetrafluoroborate (III).The methylation of (III) with diazomethane in dichloromethane ether yields 1,2-dimethyl-3-propyl-3-(3-methoxyphenyl)-1,2-ethylenepyrrolidinium tetrafluoroborate (IV),which by heating at 180 C and neutralization with NaOH affords 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)-1,4,5,6-tetrahydropyridine (V).The reduction of (V) with NaBH4 in THF gives 1,3-dimethyl-4-propyl-4-(3-methoxyphenyl)piperidine (VI),which is finally treated with 48% HBr in refluxing acetic acid.
参考文献标题:Picedanol Hydrochloride
文献作者:Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1984,9(3),204
产品链接: CAS No. 74685-16-8›› 产品链接: CAS No.79201-85-7››