(1S,3aR,6aS)-六氢-环戊[c]吡咯-1,2(1H)-二甲酸二(叔-丁基)酯 | 402960-06-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (1S,3aR,6aS)-六氢-环戊[c]吡咯-1,2(1H)-二甲酸二(叔-丁基)酯
• 英文名称: (1S,3aR,6aS)-di-tert-butyl hexahydrocyclo-penta[c]pyrrol-1,2(1H)-dicarboxylate
• 英文别名: (1S,3aR,6aS)-Di-tert-butyl hexahydrocyclopenta[c]pyrrole-1,2(1H)-dicarboxylate；ditert-butyl (3S,3aS,6aR)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2,3-dicarboxylate
• CAS: 402960-06-9
• 化学式: C₁₇H₂₉NO₄
• 分子量: 311.422
• InChiKey: REJIQUVHYOYYCK-AVGNSLFASA-N

物化性质

• 溶解度：
  溶于二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,3aR,6aS)-六氢-环戊[c]吡咯-1,2(1H)-二甲酸二(叔-丁基)酯 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以60%的产率得到(1S,3AR,6AS)-六氢环戊并[C]吡咯-1,2(1H)-二甲酸 2-叔丁酯
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF A VIRAL PROTEASE INHIBITOR AND ITS INTERMEDIATES
  [FR] PROCÉDÉ DE PRÉPARATION D'UN INHIBITEUR DE PROTÉASE VIRALE ET DE SES INTERMÉDIAIRES

  摘要：

  该申请描述了一种制备化合物（II）的过程，该化合物对于制备病毒蛋白酶抑制剂很有用。该过程的中间体也被声明。

  公开号：

  WO2013120871A1
• 作为产物：
  描述：

  3-azabicyclo[3.3.0]octane hydrochloride 在 4-二甲氨基吡啶 、 四甲基乙二胺 、 仲丁基锂 、 potassium carbonate 作用下， 以 正己烷 、 甲基叔丁基醚 、 水 、 乙酸乙酯 、 异丙醇 、 叔丁醇 为溶剂， 反应 17.0h， 生成 (1S,3aR,6aS)-六氢-环戊[c]吡咯-1,2(1H)-二甲酸二(叔-丁基)酯
  参考文献：
  名称：

  Stereoselective Lithiation and Carboxylation of Boc-Protected Bicyclopyrrolidine: Synthesis of a Key Building Block for HCV Protease Inhibitor Telaprevir

  摘要：

  A stereoselective process for the manufacture of bicyclopyrrolidine 7 to 2 has been developed. The process utilizes a stereoselective lithiation/carboxylation sequence. The achiral diamine ligand DPBP induces excellent diastereocontrol, and resolution with (S)-THNA provides the corresponding salt of 8 in high er and dr. Subsequent processing of 8 gives 2 as the oxalate salt in an overall yield of 27% from 7 (based on total molar charge of 7). Compound 2 was obtained with high chemical, and chiral purities. The process was successfully demonstrated on >100 kg scale.

  DOI：

  10.1021/op500040j

文献信息

• Peptidomimetic protease inhibitors and intermediates for their preparation As treatment for HCV infection
  申请人：Vertex Pharmaceuticals Inc.

  公开号：EP2368877B1

  公开（公告）日：2014-05-07
• US8529882B2
  申请人：——

  公开号：US8529882B2

  公开（公告）日：2013-09-10
• [EN] PROCESS FOR THE PREPARATION OF A VIRAL PROTEASE INHIBITOR AND ITS INTERMEDIATES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN INHIBITEUR DE PROTÉASE VIRALE ET DE SES INTERMÉDIAIRES
  申请人：DIPHARMA FRANCIS SRL

  公开号：WO2013120871A1

  公开（公告）日：2013-08-22

  The application describes a process for the preparation of a compound of formula (II) useful for the preparation of a viral protease inhibitor. Intermediates of the process are also claimed.

  该申请描述了一种制备化合物（II）的过程，该化合物对于制备病毒蛋白酶抑制剂很有用。该过程的中间体也被声明。
• Stereoselective Lithiation and Carboxylation of Boc-Protected Bicyclopyrrolidine: Synthesis of a Key Building Block for HCV Protease Inhibitor Telaprevir
  作者：Gerald J. Tanoury、Minzhang Chen、Yong Dong、Raymond Forslund、Valdas Jurkauskas、Andrew D. Jones、Daniel Belmont

  DOI：10.1021/op500040j

  日期：2014.10.17

  A stereoselective process for the manufacture of bicyclopyrrolidine 7 to 2 has been developed. The process utilizes a stereoselective lithiation/carboxylation sequence. The achiral diamine ligand DPBP induces excellent diastereocontrol, and resolution with (S)-THNA provides the corresponding salt of 8 in high er and dr. Subsequent processing of 8 gives 2 as the oxalate salt in an overall yield of 27% from 7 (based on total molar charge of 7). Compound 2 was obtained with high chemical, and chiral purities. The process was successfully demonstrated on >100 kg scale.