Clomoxir ethyl(Rec INNM), B-80727(free acid Na salt), B-80706, CPOC, POCA
2-[5-(4-氯苯基)戊基]环氧乙烷-2-羧酸乙酯 克罗米芬 2-[5-(4-氯苯基)戊基]环氧乙烷-2-羧酸钠Chemical Name: Ethyl 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate; 2-[5-(4-Chlorophenyl)pentyl]oxiranecarboxylic acid ethyl ester
CAS No. 78573-55-4, 88431-47-4 (free acid), 78573-70-3 (free acid Na salt)
项目整合开发状态: Preclinical
项目研究机构: Altana Pharma (Originator)
合成路线:Alkylation of diethyl malonate (II) with 5-(4-chlorophenyl)pentyl bromide (I) gives diethyl 5-(4-chlorophenyl)pentyl malonate (III).Intermediate (III) is hydrolyzed to the monoester (IV),followed by condensation with paraformaldehyde in pyridine/piperidine to yield ethyl 7-(4-chlorophenyl)-2-methyleneheptanoate (V),which is oxidized with m-chloroperbenzoic acid.Alternatively,intermediate (IV) can be prepared by condensation of 4-chlorocinnamaldehyde (VI) with diethyl ethylidenemalonate (VII) to yield intermediate (VIII) and subsequent hydrogenation.
📌 参考资料/链接：
参考文献标题:Substd.oxiranecarboxylic acids,their use and medicaments containing them
文献作者:Eistetter,K.; Rapp,E.(Byk Gulden Lomberg Chemische Fabrik GmbH)
参考来源:US 4324796
📄 详细内容
合成路线:Alkylation of diethyl malonate (II) with 5-(4-chlorophenyl)pentyl bromide (I) gives diethyl 5-(4-chlorophenyl)pentyl malonate (III).Intermediate (III) is hydrolyzed to the monoester (IV),followed by condensation with paraformaldehyde in pyridine/piperidine to yield ethyl 7-(4-chlorophenyl)-2-methyleneheptanoate (V),which is oxidized with m-chloroperbenzoic acid.Alternatively,intermediate (IV) can be prepared by condensation of 4-chlorocinnamaldehyde (VI) with diethyl ethylidenemalonate (VII) to yield intermediate (VIII) and subsequent hydrogenation.
参考文献标题:Phenylalkyloxirane carboxylic acids,preparation and therapeutical use
文献作者:Kohl,B.; Eistetter,K.; Amschler,H.; Ludwig,G.; Wolf,H.P.O.(Byk Gulden Lomberg Chemische Fabrik GmbH)
参考来源:EP 0071175
合成路线:Alkylation of diethyl malonate (II) with 5-(4-chlorophenyl)pentyl bromide (I) gives diethyl 5-(4-chlorophenyl)pentyl malonate (III).Intermediate (III) is hydrolyzed to the monoester (IV),followed by condensation with paraformaldehyde in pyridine/piperidine to yield ethyl 7-(4-chlorophenyl)-2-methyleneheptanoate (V),which is oxidized with m-chloroperbenzoic acid.Alternatively,intermediate (IV) can be prepared by condensation of 4-chlorocinnamaldehyde (VI) with diethyl ethylidenemalonate (VII) to yield intermediate (VIII) and subsequent hydrogenation.
参考文献标题:POCA
文献作者:Wolf,H.P.O.; Eistetter,K.
参考来源:Drugs Fut 1983,8(5),428
合成路线:Alkylation of diethyl malonate (II) with 5-(4-chlorophenyl)pentyl bromide (I) gives diethyl 5-(4-chlorophenyl)pentyl malonate (III).Intermediate (III) is hydrolyzed to the monoester (IV),followed by condensation with paraformaldehyde in pyridine/piperidine to yield ethyl 7-(4-chlorophenyl)-2-methyleneheptanoate (V),which is oxidized with m-chloroperbenzoic acid.Alternatively,intermediate (IV) can be prepared by condensation of 4-chlorocinnamaldehyde (VI) with diethyl ethylidenemalonate (VII) to yield intermediate (VIII) and subsequent hydrogenation.
参考文献标题:Synthesis and hypoglycaemic activity of phenylalkyloxirane carboxylic acid derivatives
文献作者:Eistetter,K.; Wolf,H.P.O.
参考来源:J Med Chem 1982,25(22),109-113