γ-联苯双酯合成

Synthesis ofγ-DDB

联苯双酯作为医药中间体以及重要肝病用药,其三种同分异构体α-联苯双酯、β-联苯双酯和γ-联苯双酯均有疗效。α-联苯双酯和β-联苯双酯通常以Ullmann偶连合成,采用Ullmann偶连合成γ-联苯双酯时会产生α-联苯双酯和β-联苯双酯,故选取Suzuki-Miyaura偶连反应合成γ-联苯双酯。本文以甲基-7-甲氧基苯并[d][1,3]二氧代-5-羧酸为初始原料,经溴化、取代反应制得苯硼酸衍生物。再经过Suzuki-Miyaura偶连反应制得γ-联苯双酯(γ-DDB)。

Diphenyl dicarboxylate is not only a medical intermediate but also a important hepatopathy medicament.Three isomers of diphenyl dicarboxylate wasα-DDB(Bifendate),β-DDB andγ-DDB,all the three isomers contain curative effect.α-DDB andβ-DDB were usually synthesized by Ullmann coupling,α-DDB andβ-DDB will be produced when theγ-DDB was synthesized by Ullmann coupling.thereforeγ-DDB was synthesized by Suzuki-Miyaura coupling reaction.Methyl-7-methoxybenzo[d][1,3]dioxole-5-carboxylate was used as raw material,via bromination reaction and substitution reaction,Phenylboronic acid derivatives was got.γ-Diphenyl dicarboxylate(γ-DDB)was formed after Suzuki-Miyaura Cross-Coupling Reaction.