合成路线:The cyclization of 2,3-dihydroxybenzaldehyde (I) with dibromomethane by means of KF in hot DMF gives 2,3-methylenedioxybenzaldehyde (II),which is condensed with ethyl acetoacetate (III) by means of piperidine and acetic acid in refluxing benzene to afford ethyl 2-acetyl-3-(2,3-methylenedioxyphenyl)acrylate (IV).Finally,this compound is cyclized with methyl 3-aminocrotonate (V) in hot isopropanol.
合成路线:Elgodipine can be obtained in three main steps:The alkylation of N-methyl-2-aminoethanol (I) with 4-fluorobenzyl chloride (II) gives 2-[N-(4-fluorobenzyl)-N-methylamino]ethanol (III),which is esterified with 2,2,6-trimethyl-4H-1,3-dioxin-4-one (IV) yielding the corresponding acetoacetic ester (V).The condensation of (V) with 2,3-methylenedioxybenzaldehyde (VI) affords 2-[N-(4-fluorobenzyl)-N-methylamino]ethyl 2-(2,3-methylenedioxybenzylidene]acetoacetate (VII),which is finally cyclized with isopropyl 3-aminocrotonate (VIII).The intermediate aldehyde (VI) is obtained starting from 2,3-dimethoxybenzaldehyde (X),which by demethylation with HCl or HBr yields 2,3-dihydroxybenzaldehyde (XI).Finally,this compound is converted into (VI) in the usual way.The intermediate crotonate (VIII) is obtained by reaction of isopropyl acetoacetate (IX) with ammonia.
参考文献标题:Oxodipine
文献作者:Serradell,M.N.; Castar,J.; Castar,R.M.
参考来源:Drugs Fut 1987,12(7),633
合成路线:Elgodipine can be obtained in three main steps:The alkylation of N-methyl-2-aminoethanol (I) with 4-fluorobenzyl chloride (II) gives 2-[N-(4-fluorobenzyl)-N-methylamino]ethanol (III),which is esterified with 2,2,6-trimethyl-4H-1,3-dioxin-4-one (IV) yielding the corresponding acetoacetic ester (V).The condensation of (V) with 2,3-methylenedioxybenzaldehyde (VI) affords 2-[N-(4-fluorobenzyl)-N-methylamino]ethyl 2-(2,3-methylenedioxybenzylidene]acetoacetate (VII),which is finally cyclized with isopropyl 3-aminocrotonate (VIII).The intermediate aldehyde (VI) is obtained starting from 2,3-dimethoxybenzaldehyde (X),which by demethylation with HCl or HBr yields 2,3-dihydroxybenzaldehyde (XI).Finally,this compound is converted into (VI) in the usual way.The intermediate crotonate (VIII) is obtained by reaction of isopropyl acetoacetate (IX) with ammonia.
参考文献标题:Elgodipine Hydrochloride
文献作者:Galiano,A.
参考来源:Drugs Fut 1995,20(3),231
产品链接: CAS No. 119413-55-7››