3-(3-fluoro-4-morpholin-4-yl-phenyl)-5-hydroxymethyl-oxazolidin-2-one | 513068-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 3-(3-fluoro-4-morpholin-4-yl-phenyl)-5-hydroxymethyl-oxazolidin-2-one
• 英文别名: 3-(3-fluoro-4-morpholinophenyl)-5-(hydroxymethyl)oxazolidin-2-one；3-{3-fluoro-4-morpholinophenyl}-5-hydroxymethyl-2-oxazolidinone；(5R)-3-(3-fluoro-4-morpholino-phenyl)-5-(hydroxymethyl)oxazolidin-2-one；3-(3-fluoro-4-morpholin-4-ylphenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one
• CAS: 513068-96-7
• 化学式: C₁₄H₁₇FN₂O₄
• 分子量: 296.298
• InChiKey: OLDRPBWULXUVTL-UHFFFAOYSA-N

物化性质

• 熔点：
  112-114 °C
• 沸点：
  494.2±45.0 °C(Predicted)
• 密度：
  1.361±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  62.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(3-fluoro-4-morpholin-4-yl-phenyl)-5-hydroxymethyl-oxazolidin-2-one 以96的产率得到3-[3-氟-4-(4-吗啉基)苯基]-5-[[(甲磺酰基)氧基]甲基]-2-恶唑烷酮
  参考文献：
  名称：

  Bull. Korean Chem. Soc. 2012, 33, 1389-1392

  摘要：

  DOI：
• 作为产物：
  描述：

  4-(2-氟-4-溴苯基)吗啉 在 copper(l) iodide 、 (1S,2S)-(+)-1,2-环己二胺 、 4-甲基苯磺酸吡啶 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 15.5h， 生成 3-(3-fluoro-4-morpholin-4-yl-phenyl)-5-hydroxymethyl-oxazolidin-2-one
  参考文献：
  名称：

  Highly Efficient CuI-Catalyzed Coupling of Aryl Bromides with Oxazolidinones Using Buchwald's Protocol:  A Short Route to Linezolid and Toloxatone

  摘要：

  [GRAPHICS]Coupling of a variety of substituted aryl bromides with oxazolidinones has been achieved using the Buchwald protocol for the amidation of aryl halides. This procedure is exemplified by the synthesis of two medicinally important molecules, linezolid and toloxatone.

  DOI：

  10.1021/ol026902h

文献信息

• Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them
  申请人：Syngenta Limited

  公开号：US20030144263A1

  公开（公告）日：2003-07-31

  Compounds of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, 1 wherein, for example, X is —O— or —S—; HET is an optionally substituted C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S; Q is selected from, for example, Q1 and Q2 2 R 2 and R 3 are independently hydrogen or fluoro; T is selected from a range of groups, for example, an N-linked (fully unsaturated) 5-membered heteroaryl ring system or a group of formula (TC5): 3 wherein Rc is, for example, R 13 CO—, R 13 SO 2 — or R 13 CS—; wherein R 13 is, for example, optionally substituted (1-10C)alkyl or R 14 C(O)O(1-6C)alkyl wherein R 14 is optionally substituted (1-10C)alkyl; are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

  式(I)的化合物，或其药学上可接受的盐，或其体内可水解的酯， 其中，例如，X为—O—或—S—； HET是一个可选择的取代的C-连接的含有2到4个异原子（独立选择自N、O和S）的5元杂芳环； Q从Q1和Q2中选择 R2和R3独立地为氢或氟； T从一系列基团中选择，例如，一个N-连接的（完全不饱和的）5元杂芳环系统或式(TC5)的基团： 其中Rc是，例如，R13CO—，R13SO2—或R13CS—； 其中R13是，例如，可选择的取代的(1-10C)烷基或R14C(O)O(1-6C)烷基 其中R14是可选择的取代的(1-10C)烷基；这些化合物可用作抗菌剂；并描述了其制备方法和含有它们的药物组合物。
• Synthesis and antibacterial activity of isothiazolyl oxazolidinones and analogous 3(2H)-isothiazolones
  作者：Neda Adibpour、Ali Khalaj、Saeed Rajabalian

  DOI：10.1016/j.ejmech.2009.09.019

  日期：2010.1

  The synthesis and antibacterial activity of several new 5-((3-oxoisothiazol-2(3H)-yl)methyl)-3-phenyloxazolidin-2-ones 8 and analogous 2-(4-substituted phenyl)-3(2H)-isothiazolones 3 and 4 substituted at 4 and/or 3-positions of the phenyl moiety with different groups of which some have shown to increase the antibacterial activity of both 3-aryl-2-oxazolidinones and 3(2H)-isothiazolones is described

  几种新的5-（（3-oxoisothiazol-2（3H）-yl）methyl）-3-phenyloxazolidin-2-ones 8和类似的2-（4-取代苯基）-3（2H）-的合成及抗菌活性描述了在苯基部分的4和/或3位被不同基团取代的异噻唑酮3和4，其中一些已显示出增加3-芳基-2-恶唑烷酮和3（2H）-异噻唑酮的抗菌活性。活性最高的化合物是异噻唑基恶唑烷酮8a，未取代的j和8b具有4-F取代苯环的化合物，对某​​些测试的微生物显示出比类似的3（2H）-异噻唑酮更高的活性，并且与利奈唑胺，万古霉素和环丙沙星具有可比或更高的活性。F的位置变化和/或使用较大的取代基使化合物的活性降低或没有活性。对小鼠成纤维细胞（NIH / 3T3）细胞的细胞毒性评估表明，这些化合物在非细胞毒性浓度下具有抗菌活性。
• Heterocyclylaminomethyloxazo-lidinones as antibacterials
  申请人：AstraZeneca AB

  公开号：US20030207899A1

  公开（公告）日：2003-11-06

  Compounds of formula (I) 1 , or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, wherein, for example, HET is an optionally substituted C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S; Q is selected from, for example, Q3 and Q5; R 2 and R 3 are independently hydrogen or fluoro; T is selected from a range of groups, for example, an N-linked (fully unsaturated) 5-membered heteroaryl ring system or a group of formula (TC5): wherein Rc is, for example, R 13 CO—, R 13 SO 2 — or R 13 CS—; wherein R 13 is, for example, optionally substituted (1-10C)alkyl or R 14 C(O)O(1-6C)alkyl wherein R 14 is optionally substituted (1-10C)alkyl; are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

  化合物的公式（I）1，或其药用盐，或其体内可水解酯，其中，例如，HET是一个含有2到4个异原子（N、O和S）的可选择取代的C-连接的5元杂环芳烃环；Q可以从Q3和Q5中选择；R2和R3独立地为氢或氟；T可以从一系列基团中选择，例如，一个N-连接的（完全不饱和的）5元杂环芳烃环系统或一个公式（TC5）的基团：其中Rc是，例如，R13CO—，R13SO2—或R13CS—；其中R13是，例如，可选择取代的（1-10C）烷基或R14C(O)O(1-6C)烷基，其中R14是可选择取代的（1-10C）烷基；作为抗菌剂是有用的；并描述了它们的制备方法和含有它们的药物组合物。
• [EN] NOVEL PROCESS FOR PREPARATION OF LINEZOLID AND ITS NOVEL INTERMEDIATES<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE LINÉZOLIDE ET SES NOUVEAUX INTERMÉDIAIRES
  申请人：LEE PHARMA LTD

  公开号：WO2012114355A1

  公开（公告）日：2012-08-30

  A novel process for preparing oxazolidinone antibacterial agent Linezolid including key intermediates of oxazolidinones comprising: reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; carbonylation to form oxazolidinone derivative; acetylation of (5R)-5-(chloromethyl)-3-(3-fluoro-4- morpholinophenyl-oxazolidin-2-one with sodium acetate to get novel intermediate; hydrolysis of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl acetate; mesylation of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol; reaction of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl methane sulphonate with potassium phthalimide; hydrolysis of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl phthalimide with hydrazine hydrate; acetylation of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl amine with acetic anhydride yields Linezolid in high yield.

  一种用于制备氧唑啉酮抗菌剂利奈唑的新工艺，包括氧唑啉酮的关键中间体，具体步骤如下：将3-氟-4-吗啉基苯胺与R-环氧氯丙烷反应；羰基化形成氧唑啉酮衍生物；将(5R)-5-(氯甲基)-3-(3-氟-4-吗啉基苯基)-氧唑啉-2-酮与醋酸钠乙酰化得到新的中间体；水解(R)-3-(3-氟-4-吗啉基苯基)-2-氧代-5-氧唑啉基甲酸甲酯；对(R)-3-(3-氟-4-吗啉基苯基)-2-氧代-5-氧唑啉基甲醇进行甲磺酰化；将(R)-3-(3-氟-4-吗啉基苯基)-2-氧代-5-氧唑啉基甲磺酸甲酯与苯酞酰胺钾反应；用水合肼水合物水解(S)-3-(3-氟-4-吗啉基苯基)-2-氧代-5-氧唑啉基甲酰胺；将(S)-3-(3-氟-4-吗啉基苯基)-2-氧代-5-氧唑啉基甲胺与乙酸酐乙酰化得到高产率的利奈唑。
• NOVEL PROCESS FOR PREPARATION OF LINEZOLID AND ITS NOVEL INTERMEDIATES
  申请人：Alla Raghu Mitra

  公开号：US20130324719A1

  公开（公告）日：2013-12-05

  A novel process for preparing oxazolidinone antibacterial agent Linezolid including key intermediates of oxazolidinones comprising: reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; carbonylation to form oxazolidinone derivative; acetylation of (5R)-5-(chloromethyl)-3-(3-fluoro-4-morpholinophenyl-oxazolidin-2-one with sodium acetate to get novel intermediate; hydrolysis of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl acetate; mesylation of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol; reaction of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl methane sulphonate with potassium phthalimide; hydrolysis of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl phthalimide with hydrazine hydrate; acetylation of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl amine with acetic anhydride yields Linezolid in high yield.

  一种制备奥沙唑啉类抗菌剂利奈唑的新型工艺，包括制备奥沙唑啉的关键中间体：将3-氟-4-吗啉基苯胺与R-环氧氯丙烷反应；羰基化形成奥沙唑啉衍生物；将（5R）-5-(氯甲基)-3-(3-氟-4-吗啉基苯基)-奥沙唑啉-2-酮与醋酸钠乙酰化以获得新型中间体；（R）-3-(3-氟-4-吗啉基苯基)-2-氧代-5-奥沙唑啉基乙酸甲酯水解；（R）-3-(3-氟-4-吗啉基苯基)-2-氧代-5-奥沙唑啉基甲醇甲磺酸酯烷基化；（R）-3-(3-氟-4-吗啉基苯基)-2-氧代-5-奥沙唑啉基甲磺酸甲酯与邻苯二甲酰亚胺钾反应；（S）-3-(3-氟-4-吗啉基苯基)-2-氧代-5-奥沙唑啉基甲酰亚胺水解；（S）-3-(3-氟-4-吗啉基苯基)-2-氧代-5-奥沙唑啉基甲胺乙酰化，得到高产率的利奈唑。