磷酸奥司他韦起始物料杂质OTg-R1的合成研究  

Synthesis of an impurity OTg-R1 in starting material of oseltamivir phosphate

作　　者：邓宇 张荣 DENG Yu;ZHANG Rong(Central Research Institute of Shanghai Pharmaceutical Group Co.,Ltd.,Shanghai 201203,China)

机构地区：[1]上海医药集团股份有限公司中央研究院,上海201203

出　　处：《上海医药》2021年第15期72-74,81,共4页Shanghai Medical & Pharmaceutical Journal

摘　　要：目的:合成磷酸奥司他韦起始物料的杂质OTg-R1。方法:以(-)-莽草酸为起始原料,经酯化反应,戊酮保护、甲烷磺酰保护,在硼烷二甲基硫醚的作用下得到混合物(OSTW-05:OTg-R1=4∶1),再经过KHCO3作用,得到可以经柱层析分离的混合物。经分离得到(3R,4R,5R)-4-(1-乙基丙氧基)-3-羟基5-[(甲基磺酰)氧]-1-环己烯-1-羧酸乙酯。结果:该目标物经质谱(MS),核磁共振氢谱(1H NMR),核磁共振碳谱(13C NMR)确证其化学结构。结论:合成的杂质可作为磷酸奥司他韦起始物料质量控制对照品;本工艺操作可行,原料易得。Objective:To synthesize an impurity OTg-R1 in a starting material of oseltamivir phosphate.Methods:Using(-)-shikimic acid as a starting material,a mixture(OSTW-05:OTg-R1=4:1)was synthesized via esterification and protection by pentanone and methane sulfonyl,from which impurity OTg-R1could be obtained by column chromatography after KHCO3 under the action of borane dimethyl sulfide.Results:The chemical structure of the OTg-R1 was confirmed by MS,1H NMR and 13C NMR.Conclusion:The synthesized impurity can be used as a reference material for the quality control of oseltamivir phosphate initiation material.This process is feasible and the raw materials are easily available.

关 键 词：磷酸奥司他韦 杂质 合成 抗流感 

分 类 号：O624.5[理学—有机化学]