瑞德西韦中间体合成技术

Synthesis Technology of Redcivir Intermediate

本研究基于瑞德西韦中间体以往合成路线的基础上,对其进行了优化设计,提出了全新的合成工艺路线,采用2-乙基-1-丁醇(化合物3)作为反应物和溶剂,同时运用SOCI2来加速酯化反应,获得盐酸盐;缚酸剂采用DIPEA,溶剂采用THF,依次将其与二氯磷酸苯酯、硝基苯酚进行作用,从而获得化合物8,再通过异丙醚析晶即可获得(3R,4R,5R)-2-(4-胺基吡咯[2,1-f][1,2,4]三嗪-7-yl)-3,4-双(苄氧基)-5-((苄氧基)甲基)四氢呋喃-2-醇。该工艺的总收率为40%。在合成工艺中,重点进行了催化剂、催化剂用量、缚酸剂、反应溶剂、温度实验,确定了最佳方案,大大简化了操作复杂度,且原料更容易获取,具有较高工业化推广价值。

Based on the previous synthetic route of redcivir intermediate,a new synthetic route was proposed.2-ethyl-1-butanol(compound 3)was used as reactant and solvent,and soci2 was used to accelerate the esterification reaction to obtain hydrochloride;Dipea is used as the acid binding agent and THF as the solvent.Compound 8 is obtained by successively reacting it with dichlorophenyl phosphate and nitrophenol.Then(3R,4R,5R)-2-(4-aminopyrrole[2,1-f][1,2,4]triazine-7-yl)-3,4-bis(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-ol can be obtained by crystallization of isopropyl ether.The total yield of the process was 40%.In the synthesis process,the experiments of catalyst,catalyst dosage,acid binding agent,reac-tion solvent and temperature are carried out,and the best scheme is determined,which greatly simplifies the operation complexity,and the raw mate-rials are easier to obtain,which has high industrial popularization value.