摘要
本研究报道了一条巴洛沙韦关键中间体3-(苄氧基)-4-氧代-4H-吡喃-2-羧酸(1)的新合成路线。以麦芽醇作为原料,经过苄基保护、缩合、氧化制得1。我们设计先将甲基间接转变成烯胺,再将烯氨氧化成醛,与甲基直接氧化成醛相比,避免使用剧毒品二氧化硒,消除了对环境的污染,并且有效提高路线的安全性。同时,本研究对烯胺的氧化条件进行了选择与优化,先将烯胺氧化成醛,醛中间体无需分离,进一步氧化到羧酸,“一锅法”实现了两个氧化历程,并且避免使用昂贵的钌催化剂,大幅度降低成本。总收率69.7%,产品纯度99.26%。
We reported a new synthetic route for baloxavir’s key intermediate 3-(benzyloxy)-4-oxo-4H-pyran-2-carboxylic acid(1).Maltol was used as the material and 1 was prepared by benzyl protection,condensation and oxidation.We designed the indirect conversion of methyl into enamine and then the oxidation of enamine into aldehyde.Compared with the direct oxidation of methyl into aldehyde,the new rout could avoid the use of selenium dioxide,eliminate the pollution to the environment and effectively improve the safety of the synthesis.Meanwhile,the oxidation conditions of enamine were selected and optimized in this study.The enamine was oxidized to aldehyde first,and the aldehyde intermediate was further oxidized to carboxylic acid without separation.The“one-pot method”realized two oxidation processes and avoided the use of expensive ruthenium catalyst,which could greatly reduce the cost.The total yield was 69.7%and the purity was 99.26%.
作者
于立国
孙光祥
张云然
陶维洁
YU Liguo;SUN Guangxiang;ZHANG Yunran;TAO Weijie(Changzhou Pharmaceutical Factory,Shanghai Pharmaceutical Group,Changzhou 213018,China)
出处
《上海医药》
CAS
2022年第1期67-69,共3页
Shanghai Medical & Pharmaceutical Journal
关键词
巴洛沙韦
产业化
合成
baloxavir
industrialization
synthesis
