【摘要】 以酒石酸为起始原料,经硝化、环合、酯化、格利雅反应、N-烃化、水解、O-烃化、水解去保护等反应制得奥美沙坦,总收率32.7%。目标化合物及各关键中间体的结构均经MS,1H-NMR,IR分析确证,并对反应条件进行了改进。2-丙基咪唑二羧酸(2)采用酒石酸用混酸硝化后与醛氨溶液缩合制得,避免了文献中所用有毒的2,3-二氨基丁烯二腈。N-烃化以价廉易得的氢氧化钾代替叔丁醇钾、氢化钠。在水解反应中以氢氧化钠代替氢氧化锂,反应时间由20h缩短为2h。O-烃化以丙酮代替二甲基乙酰胺作溶剂,后处理更加简便。整条合成路线条件温和、操作简单、成本低廉,较适合于工业化生产。更多还原

【Abstract】 In this paper, a new angiotensin Ⅱ receptor antagonist, (5-methyl-2-oxo-1,3-dioxol-4-yl)　methyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2′-1H-tetrazol-5-yl-biphenyl-4-yl) methyl] imdazole-5-carboxylate(Olmesartan medoxomil), was synthesized using tartaric acid as starting material via nitration, cyclization, esterifcation, Grignard reaction, N-alkylation, hydrolyzation, O-alkylation and N-deprotection in 32.7% overall yield. The structure of title compound has been characterized by MS(mass spectrum), (()~1H)-NMR (nuclear magnetic resonance) and IR (ifrared spectrum). The condensation of 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester with 5-[4′-(bromomethyl) biphenyl-2-yl]-1-(triphenylmethyl) tetrazole by means of potassium hydroxide in DMF, instead of potassium tert-butoxide in dimethylacetamide or sodium hydroxide in DMF, gives the corresponding N-alkylated product, which is hydrolyzed with sodium hydroxide, instead of lithium hydroxide, in dioxane-water to the desired acid. The improved process is more practical.更多还原