地瑞那韦中间体(3aS,6aR)-9-顺-四氢-4-甲氧基呋喃并[3,4b]呋喃-2(3H)-酮产品中微量杂质的分析和形成机理
Analysis and Formation Mechanism of Trace Impurity in Darunavir Key Intermediate: (3aS,6aR)-9-cis-Tetrahydrogen-4-Methoxyfuran[3,4b]Furan-2(3H)-One
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摘要: 对抗艾滋病药地瑞那韦(Darunavir)的关键中间体(3aS,6aR)-9-顺-四氢-4-甲氧基呋喃并[3,4b]呋喃-2(3H)-酮(MFO)产品中的微量杂质进行了富集与提纯,运用高分辨质谱、元素分析、核磁共振、单晶X射线衍射等技术对其进行了分析,确定该杂质为MFO的二聚体,是已知杂质α-DIMFO的差向异构体(简称为β-DIMFO)。并探讨了该杂质的形成机理。Abstract: The trace impurity in (3aS,6aR)-9-cis-tetrahydrogen-4-methoxyfuran[3,4b]furan-2(3H)-one(MFO)is enriched and purified. The impurity was identified by high resolution MS, elemental analysis, NMR, and monocrystal X-ray diffraction, and its structrue is a new dimer of MFO(β-DIMFO), which is an epimer of known impurity, α-DIMFO. Formation mechanism of the impurity is discussed.