艾司洛尔中间体3-(4-羟基苯基)丙酸甲酯的合成

Synthesis of an esmolol intermediate of methyl 3-(4-hydroxyphenyl)propionate

在前人研究的基础上,我们设计并实施了一条艾司洛尔中间体3-(4-羟基苯基)丙酸甲酯的合成新路线.以对甲基苯酚和乙酸酐为原料,进行酰化反应得到乙酸(4-甲基)苯酚酯,经过溴化反应得到乙酸(4-溴代亚甲基)苯酚酯后,与丙二酸二乙酯进行取代反应得到关键中间体[[4-(乙酰氧基)苯基]甲基]-1,3-丙二酸二乙酯.再脱羧、水解和酸化,得到对羟基苯丙酸.最终经酯化反应得到3-(4-羟基苯基)丙酸甲酯,总收率49.8%.在酯化反应、溴代反应和过程操作上实施了进一步优化,使得本路线原料易得,操作简捷,反应条件温和,因此,具有一定潜在工业化前景.

On the basis of previous studies,we designed and implemented a new synthetic route for esmolol intermediate methyl 3-(4-hydroxyphenyl)propionate.Taking p-methylphenol and acetic anhydride as raw materials,we obtain(4-methyl)phenol acetate by acylation reaction.We obtained(4-bromomethylene)phenol acetate after bromination reaction,and using the substitution reaction with diethyl malonate to obtain the key intermediate 2-[[4-(acetoxy)phenyl]methyl]-1,3-diethyl malonate.With decarboxylation,hydrolysis and acidification reactions of intermediate,p-hydroxyphenylpropionic acid was prepared.After being further esterification reaction,3-(4-hydroxybenzene)methyl propionate was yielded with a total yield of 49.8%.Further optimization conditions were carried out in the esterification reaction,bromination reaction and process operation,which made this route easy to obtain raw materials,simple operation and mild reaction conditions.Therefore,this routes has a certain potentially industrial prospect.