ethyl (R)-3-azido-4-(2,4,5-trifluorophenyl)butyrate | 1352613-33-2

• 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: ethyl (R)-3-azido-4-(2,4,5-trifluorophenyl)butyrate
• 英文别名: ethyl (3R)-3-azido-4-(2,4,5-trifluorophenyl)butanoate
• CAS: 1352613-33-2
• 化学式: C₁₂H₁₂F₃N₃O₂
• 分子量: 287.241
• InChiKey: KBELBGHZTBHYPT-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  40.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl (S)-3-methansulfonyloxy-4-(2,4,5-trifluorophenyl)butyrate 在 N-甲基甲酰胺 、 sodium azide 作用下， 以 环丁砜 为溶剂， 反应 7.0h， 生成 ethyl (R)-3-azido-4-(2,4,5-trifluorophenyl)butyrate
  参考文献：
  名称：

  Process for the synthesis of beta-amino acids and derivatives thereof

  摘要：

  本发明涉及一种制备β-氨基酸及其衍生物的方法，该方法特别适用于格列酮类药物，尤其是西他列汀。关键步骤利用适当衍生的环氧化物或氮杂环丙烷，由于手性而为中间体提供手性来源，适用于构建β-氨基酸和类似化合物，特别是在构建西他列汀分子时。

  公开号：

  EP2397141A1

文献信息

• METHOD FOR PREPARING SITAGLIPTIN INTERMEDIATE VIA ASYMMETRICAL REDUCTION METHOD
  申请人：ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.

  公开号：US20170305822A1

  公开（公告）日：2017-10-26

  Disclosed is a method for synthesizing a sitagliptin intermediate, the method comprising: in the presence of hydrogen and a transition metal catalyst having a chiral phosphine ligand, subjecting a compound of formula II to an asymmetric reductive amination with ammonia or ammonium salt in a proper organic solvent under the condition of adding an acidic additive to produce a compound of formula I, wherein, an R- or S-configuration of a stereocenter is represented by *; the compound of formula I of R configuration can be used to prepare sitagliptin, and a reaction formula is as follows: R 1 and R 2 are each independently selected from hydrogen, C 1 -C 12 linear or branched alkyl, C 3 -C 12 cycloalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl and C 7 -C 12 arylalkyl. The method has a high yield and a high ee % value, a mild reaction condition and a low production cost, and is simple to operate, convenient to purify, environmental friendly and suitable for industrial production.

  本发明公开了一种合成西格列汀中间体的方法，该方法包括：在氢和具有手性膦配体的过渡金属催化剂的存在下，在适当的有机溶剂中加入酸性添加剂的条件下，将式II化合物经过不对称还原胺化反应与氨或铵盐反应，生成式I化合物，其中，立体中心的R-或S-构型由*表示；R构型的式I化合物可用于制备西格列汀，反应式如下：其中，R1和R2分别独立地选自氢、C1-C12线性或支链烷基、C3-C12环烷基、C2-C12烯基、C2-C12炔基和C7-C12芳基烷基。该方法具有高产率和高ee％值，反应条件温和，生产成本低，操作简单，易于纯化，环保友好，适用于工业生产。
• Method for preparing sitagliptin intermediate via asymmetrical reduction method
  申请人：ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.

  公开号：US10189760B2

  公开（公告）日：2019-01-29

  Disclosed is a method for synthesizing a sitagliptin intermediate, the method comprising: in the presence of hydrogen and a transition metal catalyst having a chiral phosphine ligand, subjecting a compound of formula II to an asymmetric reductive amination with ammonia or ammonium salt in a proper organic solvent under the condition of adding an acidic additive to produce a compound of formula I, wherein, an R- or S-configuration of a stereocenter is represented by *; the compound of formula I of R configuration can be used to prepare sitagliptin, and a reaction formula is as follows: R1 and R2 are each independently selected from hydrogen, C1-C12 linear or branched alkyl, C3-C12 cycloalkyl, C2-C12 alkenyl, C2-C12 alkynyl and C7-C12 arylalkyl. The method has a high yield and a high ee % value, a mild reaction condition and a low production cost, and is simple to operate, convenient to purify, environmental friendly and suitable for industrial production.

  本发明公开了一种合成西格列汀中间体的方法，该方法包括在氢和具有手性膦配体的过渡金属催化剂存在下，在加入酸性添加剂的条件下，使式II化合物在适当的有机溶剂中与氨或铵盐进行不对称还原胺化反应，生成式I化合物，其中，立体中心的R构型或S构型用*表示；R构型的式I化合物可用于制备西格列汀，反应式如下：R1和R2各自独立地选自氢、C1-C12直链或支链烷基、C3-C12环烷基、C2-C12烯基、C2-C12炔基和C7-C12芳烷基。该方法收率高、ee % 值高、反应条件温和、生产成本低，且操作简单、净化方便、环境友好，适合工业化生产。