摘要
目的 改进依折麦布的合成工艺.方法 以4-羟基苯甲醛为起始原料,经苄基保护、缩合得到中间体N-(4-氟苯基)4.苄氧基苯亚甲胺(4);以氟苯为起始原料,经傅克酰化、还原、酯化反应得到中间体6-(4-氟苯基)四氢-2H-吡喃-2-酮(9);中间体4与中间体9经环合、氧化、还原、脱保护、拆分共10步反应得到依折麦布.结果与结论 目标化合物依折麦布的结构经MS、1 H-NMR谱确证,反应总收率达6.2％(以4-羟基苯甲醛计),化学纯度大于99.5％.
Abstract
Ezetimibe is a cholesterol absorption inhibitor developed by Merck Corporation and ScheringPlough Corporation.In this paper,a new synthetic route for preparing ezetimibe was designed on the base of several references,synthesized from a convergent synthesis.Intermediate 4,N-(4-fluorophenyl)-4-benzyloxybenzimide,was obtained via benzyl protection,condensation reaction,using 4-hydroxybenzaldehyde as the starting material;Intermediate 9,6-(4-fluorophenyl) tetrahydro-2H-pyran-2-one,was obtained via FriedelCrafts alkylation,reduction,esterification,using fluorobenzene as the starting material.The final product was prepared via cyclization of intermediates 4 and 9,oxidation,reduction,deprotection,chiral separation,with an overall yield of 6.2％.The structure of the target compound was confirmed by MS and 1H-NMR.
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维普
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