罗沙司他新中间体的合成技术研究  

Study on the Synthesis of New Intermediate of Roxadustat

作　　者：王明光 张滨 Wang Ming-guang;Zhang Bin

机构地区：[1]浙江美诺华药物化学有限公司,浙江上虞312369

出　　处：《化工设计通讯》2022年第2期202-204,共3页Chemical Engineering Design Communications

摘　　要：开发罗沙司他的新中间体合成技术,降低中间体成本,简化操作,节能减排。以对氟苯甲酰氯为原料,在N-(1-甲基乙基)-2-丙胺保护、氮气保护下正丁基锂拔氢后与乙醛反应,酸性条件下关环后再与苯酚反应得到关键中间体。原料和反应试剂廉价易得,成本低,合成方法的安全性高,操作简单,总体收率高,四步总收率可达到60%以上,中间体纯度可达到98.5%以上。该新中间体成本低廉,操作条件温和、安全、中间体纯度高,可替代原研中间体作为下步合成技术的开发和应用。To develop new intermediate synthesis technology of Roxadustat,reduce intermediate cost,simplify operation,save energy and reduce emission.Using p-fluorobenzoyl chloride as raw material,the key intermediate was synthesized by the reaction of p-fluorobenzoyl chloride with Acetaldehyde after hydrogen extraction under N-(1-methyl Ethyl)-2-propylamine protection and nitrogen protection,and then reacted with phenol after ring closing under acid condition.The raw materials and reaction reagents are cheap and available,the cost is low,the synthetic method is safe,the operation is simple,the overall yield is high,the total yield of four steps can reach over 60%,the purity of intermediate can reach over 98.5%.The new intermediate has the advantages of low cost,mild operating conditions,safety and high purity.It can be used as a substitute for the original intermediate in the next step.

关 键 词：罗沙司他新中间体 合成技术 收率 

分 类 号：TQ460.1[化学工程—制药化工]