磷酸奥司他韦起始物料杂质OTg-R1的合成研究
邓宇 张荣摘 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。
关键词 磷酸奥司他韦 杂质 合成 抗流感
中图分类号:O624.5 文献标志码:A 文章编号:1006-1533(2021)15-0072-03
Synthesis of an impurity OTg-R1 in starting material of oseltamivir phosphate
DENG Yu, ZHANG Rong
(Central Research Institute of Shanghai Pharmaceutical Group Co., Ltd., Shanghai 201203, China)
ABSTRACT 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 ......
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