合成路线:Initially,a small-scale synthetic route to idoxifene had been described involving Friedel-Crafts acylation of 2-chloroethoxybenzene by 2-phenylbutyric acid followed by reaction of the resulting ketone with 4-iodophenyllithium (prepared by monolithiation of 1,4-diiodobenzene) .A mixture of E and Z isomers of the triphenylbutene was then produced by dehydration of the intermediate tertiary alcohol from which the desired E isomer (in which the unsubstituted phenyl and iodophenyl residues are in a trans relationship) was separated by crystallization.Idoxifene was then produced by final modification of the chloroethoxy side chain using pyrrolidine.Modification of the above scheme to provide an efficient,large-scale synthesis of idoxifene has now been described initially involving treatment of 2-phenoxyethanol with pyridine (in catalytic amounts) and thionyl chloride/heat to produce 2-chloroethoxybenzene.
参考文献标题:Idoxifene
文献作者:Kelland,L.R.; Jarman,M.
参考来源:Drugs Fut 1995,20(7),666
合成路线:Initially,a small-scale synthetic route to idoxifene had been described involving Friedel-Crafts acylation of 2-chloroethoxybenzene by 2-phenylbutyric acid followed by reaction of the resulting ketone with 4-iodophenyllithium (prepared by monolithiation of 1,4-diiodobenzene) .A mixture of E and Z isomers of the triphenylbutene was then produced by dehydration of the intermediate tertiary alcohol from which the desired E isomer (in which the unsubstituted phenyl and iodophenyl residues are in a trans relationship) was separated by crystallization.Idoxifene was then produced by final modification of the chloroethoxy side chain using pyrrolidine.Modification of the above scheme to provide an efficient,large-scale synthesis of idoxifene has now been described initially involving treatment of 2-phenoxyethanol with pyridine (in catalytic amounts) and thionyl chloride/heat to produce 2-chloroethoxybenzene.
参考文献标题:An efficient,large-scale synthesis of idoxifene ((E)-1-[4-[N-(pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene)
文献作者:Potter,G.A.; Jarman,M.; McCague,R.
参考来源:Org Prep Proced Int 1994,26343-6
合成路线:A synthesis of iodine radiolabeled idoxifene has been published: The reaction of the tributylstannyl precursor (I) with 125INa and chloramine T in dichloromethane.
参考文献标题:NCA radioiodination of idoxifene
文献作者:Hammersley,P.; Trivedi,M.; Young,H.; Carnochan,P.; Potter,G.; Ott,R.; Jarman,M.
参考来源:J Label Compd Radiopharm 1995,36(10),921
合成路线:The reaction of 2-phenylbutyric acid (I) with LDA gives the enolate (II),which is condensed with ethyl 4-iodobenzoate (III) to yield the not isolated intermediate (IV),which decarboxylates to afford 1-(4-iodophenyl)-2-phenyl-1-butanone (V).The Grignard reaction of the ketone (V) with 4-[2-(1-pyrroliidnyl)ethyl]phenylmagnesium bromide (VI) (obtained from the corresponding bromobenzene (VII) and Mg in THF) affords the tertiary alcohol (VIII),which is esterified with pivaloyl chloride (IX) and KHMDS to provide the pivalate (X).Finally,this compound is treated with hexamethyldisylazane at 165 C to provide the target ethylene.
参考文献标题:Development of an efficient and stereoselective manufacturing route to idoxifene
文献作者:Ace,K.W.; et al.
参考来源:Org Process Res Dev 2001,5(5),479
产品链接: CAS No. 116057-75-1››