Loperamide oxide, JKD-584, R-58425, Arestal
氧洛哌丁胺Chemical Name: trans-4-(4-Chlorophenyl)-4-hydroxy-N,N-dimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide N-oxide
CAS No. 106900-12-3
项目整合开发状态: Discontinued
项目研究机构: Janssen (Originator), Janssen-Kyowa (Originator), Dainippon Pharmaceutical (Licensee)
合成路线:Treatment of 2-oxo-3,3-diphenyl-tetrahydrofuran (I) with HBr(g) yields bromo derivative (II),which is then converted into butyryl chloride derivative (III) by means of thionyl chloride in refluxing chloroform.Reaction of derivative (III) with dimethylamine (IV) in toluene affords dimethyl (tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide (V),which is then condensed with 4-(4-chlorophenyl)-4-piperidinol (VI) by means of Na2CO3 and KI in refluxing 4-methyl-2-pentanone to provide N,N-dimethyl butyramide derivative (VII).Finally,the target product is obtained by N-oxidation of the piperidine ring in (VII) by heating with H2O2 in MeOH/methylbenzene or in 4-methyl-2-pentanone.
📌 参考资料/链接：
参考文献标题:Novel alpha,alpha-diaryl-4-aryl-4-hydroxy-1-piperidinebutanamide,N-oxides
文献作者:Cooymans,L.P.; Wals,L.(Janssen Pharmaceutica NV)
参考来源:EP 0219898; JP 1987087569; US 4824853; US 4898873.
📄 详细内容
合成路线:Treatment of 2-oxo-3,3-diphenyl-tetrahydrofuran (I) with HBr(g) yields bromo derivative (II),which is then converted into butyryl chloride derivative (III) by means of thionyl chloride in refluxing chloroform.Reaction of derivative (III) with dimethylamine (IV) in toluene affords dimethyl (tetrahydro-3,3-diphenyl-2-furylidene)ammonium bromide (V),which is then condensed with 4-(4-chlorophenyl)-4-piperidinol (VI) by means of Na2CO3 and KI in refluxing 4-methyl-2-pentanone to provide N,N-dimethyl butyramide derivative (VII).Finally,the target product is obtained by N-oxidation of the piperidine ring in (VII) by heating with H2O2 in MeOH/methylbenzene or in 4-methyl-2-pentanone.
参考文献标题:2,2-Diaryl-4-(4'-aryl-4'-hydroxy-piperidino)-butyramides
文献作者:Niemegeers,C.J.E.J.; Janssen,P.A.J.; Stokbroekx,R.A.; Vandenberk,J.(Janssen Pharmaceutica NV)
参考来源:US 3714159.
产品链接: CAS No. 106900-12-3››