(S)-4-benzyl-3-((S)-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl)oxazolidin-2-one | 1104077-74-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-4-benzyl-3-((S)-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl)oxazolidin-2-one
• 英文别名: (S)-4-benzyl-3-[(S)-3-(3,5-difluoro-phenyl)-4,4,4-trifluoro-butyryl]-oxazolidin-2-one；(4S)-4-benzyl-3-[(3S)-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl]-1,3-oxazolidin-2-one
• CAS: 1104077-74-8
• 化学式: C₂₀H₁₆F₅NO₃
• 分子量: 413.344
• InChiKey: OSFFQDBQZLXWDI-IRXDYDNUSA-N

物化性质

• 熔点：
  127-128 °C
• 沸点：
  477.1±45.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-4-benzyl-3-((S)-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl)oxazolidin-2-one 在 双(三甲基硅烷基)氨基钾 、 2,4,6-三异丙基苯磺酰叠氮化物 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.5h， 生成 C₂₀H₁₅F₅N₄O₃
  参考文献：
  名称：

  实用的对映选择性合成3-芳基-3-三氟甲基-2-氨基丙醇衍生物

  摘要：

  描述了开发大规模对映选择性合成包含3-芳基-3-三氟甲基-2-氨基丙醇核的铅化合物的方法。通过珀金缩合或霍纳-沃兹沃思-埃蒙斯烯化反应制备3,3-二取代丙烯酸衍生物的单一异构体，然后进行水解。将该酸转化为手性丙烯恶唑烷酮衍生物。后者在MgBr 2存在下在Pd / C上的氢化反应是通过螯合控制的构象进行的，以高选择性产生所需的异构体。随后的Evans叠氮化，氢化，手性助剂的还原裂解和磺酰化以高总收率提供了作为单一异构体的目标化合物。

  DOI：

  10.1021/op900216v
• 作为产物：
  描述：

  (S,E)-4-benzyl-3-(3-(3,5-difluorophenyl)-4,4,4-trifluorobut-2-enoyl)oxazolidin-2-one 在 palladium 10% on activated carbon 、 氢气 、 magnesium bromide 作用下， 以 四氢呋喃 为溶剂， 45.0~50.0 ℃ 、549.5 kPa 条件下， 反应 4.0h， 生成 (S)-4-benzyl-3-((S)-3-(3,5-difluorophenyl)-4,4,4-trifluorobutanoyl)oxazolidin-2-one
  参考文献：
  名称：

  实用的对映选择性合成3-芳基-3-三氟甲基-2-氨基丙醇衍生物

  摘要：

  描述了开发大规模对映选择性合成包含3-芳基-3-三氟甲基-2-氨基丙醇核的铅化合物的方法。通过珀金缩合或霍纳-沃兹沃思-埃蒙斯烯化反应制备3,3-二取代丙烯酸衍生物的单一异构体，然后进行水解。将该酸转化为手性丙烯恶唑烷酮衍生物。后者在MgBr 2存在下在Pd / C上的氢化反应是通过螯合控制的构象进行的，以高选择性产生所需的异构体。随后的Evans叠氮化，氢化，手性助剂的还原裂解和磺酰化以高总收率提供了作为单一异构体的目标化合物。

  DOI：

  10.1021/op900216v

文献信息

• PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF HETEROCYCLIC SULFONAMIDE COMPOUNDS
  申请人：Alimardanov Asaf

  公开号：US20090023930A1

  公开（公告）日：2009-01-22

  Methods for preparing compound of formula (I) are described, wherein R 1 -R 3 are defined herein, as are methods for preparing the intermediates formed therein. Also described are methods for enantioselectively preparing a chiral compound of the following structure, wherein R 2 and R 3 are defined herein.

  描述了制备式(I)化合物的方法，其中R1-R3在此处定义，以及制备其中间体的方法。还描述了选择性对映体制备具有以下结构的手性化合物的方法，其中R2和R3在此处定义。
• PROCESS FOR THE PREPARATION OF TRIFLUOROALKYL-PHENYL AND HETEROCYCLIC SULFONAMIDES
  申请人：Connolly Terrence Joseph

  公开号：US20090023903A1

  公开（公告）日：2009-01-22

  A novel trifluoroacetylating agent, i.e., N-trifluoroacetylmorpholine, is described. This reagent is useful in the preparation of phenyl and heterocyclic sulfonamide compounds. Methods are therefore described for preparing sulfonamide compounds of the following structure, wherein R 1 and R 2 are defined herein, using N-trifluoroacetylmorpholine. The sulfonamide compounds that may be prepared as described herein include 5-chloro-thiophene-2-sulfonic acid [(1S,2R)-2-(3,5-difluoro-phenyl)-3,3,3-trifluoro-1-hydroxymethyl-propyl]-amide using N-trifluoroacetylmorpholine.

  描述了一种新型三氟乙酰化试剂，即N-三氟乙酰吗啡啶。该试剂可用于制备苯基和杂环磺酰胺化合物。因此，描述了使用N-三氟乙酰吗啡啶制备以下结构的磺酰胺化合物的方法，其中R1和R2在此处定义。根据所述方法可制备的磺酰胺化合物包括使用N-三氟乙酰吗啡啶的5-氯噻吩-2-磺酸[(1S,2R)-2-(3,5-二氟苯基)-3,3,3-三氟-1-羟甲基丙基]-酰胺。
• [EN] PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF HETEROCYCLIC SULFONAMIDE COMPOUNDS<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES POUR LA PRÉPARATION DE COMPOSÉS SULFONAMIDE HÉTÉROCYCLIQUES
  申请人：WYETH CORP

  公开号：WO2009012203A1

  公开（公告）日：2009-01-22

  Methods for preparing compound of Formula (I) are described, wherein R1-R3 are defined herein, as are methods for preparing the intermediates formed therein. Formula (I) Also described are methods for enantioselectively preparing a chiral compound of the following structure, wherein R2 and R3 are defined herein. Formula (II).

  本文描述了制备式(I)化合物的方法，其中R1-R3如本文所定义，并描述了制备其中间体的方法。式(I)。还描述了对具有以下结构的手性化合物进行对映选择性制备的方法，其中R2和R3如本文所定义。式(II)。
• <i>In Situ</i> FTIR Study and Scale-Up of An Enolization−Azidation Sequence
  作者：Terrence J. Connolly、Eric C. Hansen、Michael F. MacEwan

  DOI：10.1021/op900299c

  日期：2010.3.19

  A key step in the synthesis of all optically active aminoalcohol-containing active pharmaceutical ingredient (API) involved the diastereoselective introduction of an azido functional group on a functionalized chiral oxazolidinone. This was accomplished via a low-temperature enolization, followed by a quench with triisopropylbenzenesulfonyl azide. To enable scale-up of this process, the enolization temperature had to be increased from the original < -65 degrees C to approximately -40 degrees C. In situ FTIR was used to study the enolization and quench stages of the reaction. The half-life of the enolate at -45 degrees C was estimated to Ile 12 h oil the basis of in situ FTIR profiling. Examination of the in situ FTIR data also provided evidence that the reaction between the enolate and triisopropylbenzenesulfonyl azide was instantaneous and demonstrated that accumulation of triisopropylbelizenesulfonyl azide did not occur. A combination of in situ FTIR experiments and traditional parameter ranging experiments resulted in a process that was successfully run at -40 degrees C without all appreciable erosion of facial selectivity or yield.
• Modified Chelation-Controlled Reduction of an <i>N</i>-Acryloyloxazolidin-2-one
  作者：Terrence J. Connolly、Zhixian Ding、Yumin Gong、Michael F. MacEwan、Jan Szeliga、Asaf Alimardanov

  DOI：10.1021/op100074m

  日期：2010.11.19

  A key step in the synthesis of an optically active aminoalcohol-containing active pharmaceutical ingredient (API) involved the diasteroselective reduction of a chiral 3-acryloyl-4-benzyloxazolidin-2-one. Preliminary work identified that excellent facial selectivity could be achieved by performing the hydrogenation in tetrahydrofuran in the presence of magnesium bromide. During an intermediate scale-up to support a 500-g batch of API, a side reaction between the product and magnesium bromide was observed that led to a significant deterioration in the isolated yield of product. An examination of alternative chelators and processing solvents identified that magnesium chaloride in 2-methyltetrahydrofuran offered comparable facial selectivity with significantly diminished liabilities for scale-up. This revised process was incorporated into campaigns to produce larger lots of API and afforded the product in 85% yield, averaged over 18 batches.