4-羟基-N-BOC-2-氧代脯氨酸 | 409341-03-3

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 脯氨酸类衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 4-羟基-N-BOC-2-氧代脯氨酸
• 中文别名: 4-羟基-N-Boc-2-氧代脯氨酸；4-羟基-2-氧代吡咯烷-1-羧酸叔丁酯
• 英文名称: tert-butyl 4-hydroxy-2-oxopyrrolidine-1-carboxylate
• 英文别名: (±)-N-boc-4-hydroxy-2-pyrrolidinone；(+/-)-tert-butyl-4-hydroxy-2-oxo-pyrrolidinecarboxylate
• CAS: 409341-03-3
• 化学式: C₉H₁₅NO₄
• mdl: MFCD09953075
• 分子量: 201.222
• InChiKey: GUVYWSACSIYEDN-UHFFFAOYSA-N

物化性质

• 沸点：
  360.6±35.0 °C(Predicted)
• 密度：
  1.254±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.777
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-羟基-N-BOC-2-氧代脯氨酸 在 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.5h， 生成 2-氧代-2,5-二氢-吡咯-1-羧酸叔丁酯
  参考文献：
  名称：

  一种用于合成 N-Boc-2-叔丁基二甲基甲硅烷氧基吡咯的高效可扩展工艺

  摘要：

  描述了一种用于制备 N-Boc-2-叔丁基二甲基甲硅烷氧基-吡咯 (TBSOP) 的安全、可靠和可扩展的工艺。在三步中，一锅序列 (±)-4-amino-3-hydroxybutyric 酸被转化为 N-Boc-4-hydroxy-2-pyrrolidinone。通过过滤直接从反应混合物中分离出这种稳定的结晶产物。脱水后烯醇化和甲硅烷基化产生目标化合物，无需色谱纯化。该工艺已在中试工厂中得到证明，以 85% 的总产率生产多公斤材料。

  DOI：

  10.1021/op025532+
• 作为产物：
  描述：

  4-氨基-3-羟基丁酸 、 二碳酸二叔丁酯 、 triethylamine tris(hydrogen fluoride) 在 4-二甲氨基吡啶 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 吡啶 、 正庚烷 为溶剂， 以41 g (97%)的产率得到4-羟基-N-BOC-2-氧代脯氨酸
  参考文献：
  名称：

  Process for the preparation of substituted pyrrolidine neuraminidase inhibitors

  摘要：

  一种用于制备具有结构式（28）1或其治疗上可接受的盐的神经氨酸酶抑制剂的方法，其中R1是烷基，环烷基，环烷基烷基或芳基烷基；R2是烷基，环烷基，环烷基烷基或芳基烷基；R4是烷基，环烷烷基或芳基（C2-C4-烷基）；R10是甲基，乙基，异丙基或乙烯基；和R12是氢或烷基，公开了用于该方法的中间体。

  公开号：

  US20030055297A1

文献信息

• HETEROARYLPHENOXY BENZAMIDE KAPPA OPIOID LIGANDS
  申请人：Pfizer Inc.

  公开号：US20180148432A1

  公开（公告）日：2018-05-31

  The present invention provides compounds of Formula I: and pharmaceutically acceptable salts thereof wherein the variables R 1 , R 2 , R 3 , R 4 , R 9 , X, m and n are as defined herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating kappa opioid (κ-opioid) associated disorders including, e.g., a neurological disorder, or psychiatric disorder such as a neurocognitive disorder, substance abuse disorder, depressive disorder, anxiety disorder, trauma and stressor related disorder and feeding and eating disorder.

  本发明提供了Formula I的化合物及其药用盐，其中变量R1、R2、R3、R4、R9、X、m和n如本文所定义；制备方法；用于制备的中间体；含有这些化合物或盐的组合物，以及它们用于治疗κ-阿片受体相关疾病的用途，例如神经系统疾病，或精神障碍，如神经认知障碍、物质滥用障碍、抑郁障碍、焦虑障碍、创伤和应激相关障碍以及进食障碍。
• Process for preparing optically active 4-hydroxy-2-pyrrolidinone and n-substituted 4-hydroxy-2-pyrrolidinones by enzymatic hydroxylation
  申请人：——

  公开号：US20040009562A1

  公开（公告）日：2004-01-15

  This invention provides a process for the preparation of optically active 4-hydroxy-2-pyrrolidinone or N-substituted 4-hydroxy-2-pyrrolidinones, wherein an oxygen atom is inserted regio- and stereoselectively into the corresponding non-hydroxylated 2-pyrrolidinones, by using, as a biocatalyst, a microorganism having hydroxylation activity, or a host-organism having the gene(s) necessary for the hydroxylation enzymes derived from the said microorganism, or an enzyme having hydroxylation activity derived from the above microorganisms. The microorganism may be selected from the group consisting of microorganisms that degrade alkanes or cyclic hydrocarbons, microorganisms having alkane hydroxylase(s), or microorganisms that are able to oxidize hydrocarbons.

  本发明提供了一种制备光学活性4-羟基-2-吡咯烷酮或N-取代的4-羟基-2-吡咯烷酮的方法，其中将氧原子以区域和立体选择性插入相应的非羟基化2-吡咯烷酮中，使用具有羟化活性的微生物或具有来自所述微生物的羟化酶所必需的基因的宿主生物作为生物催化剂，或者使用来自上述微生物的羟化酶活性的酶。微生物可以从降解烷烃或环烃的微生物、具有烷烃羟化酶的微生物或能够氧化碳氢化合物的微生物中选择。
• N-Tert-Butoxycarbonyl-2-Pyrrolidinones and Production Method Thereof
  申请人：Hirata Norihiko

  公开号：US20100280259A1

  公开（公告）日：2010-11-04

  N-tert-butoxycarbonyl-2-pyrrolidinones represented by the following formula (1). In the formula (1), R1, R2, R3, R4, R5 and R6 independently represent a hydrogen atom, a halogen atom, a cyano group, a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, which may have a substituent, a linear, branched or cyclic alkenyl group having 2 to 10 carbon atoms, which may have a substituent, or the like, R1 and R2 may be linked to form a >C═O group along with the carbon atom to which both are attached, R3 and R4 may be linked to form a >C═O group along with the carbon atom to which both are attached, R5 and R6 may be linked to form a >C═O group along with the carbon atom to which both are attached, or any two among R1, R2, R3, R4, R5 and R6 may be linked to form a polymethylene group having 1 to 4 carbon atoms which may have a substituent.

  以下公式（1）表示N-tert-丁氧羰基-2-吡咯酮。在公式（1）中，R1，R2，R3，R4，R5和R6独立地表示氢原子，卤素原子，氰基，具有1到10个碳原子的线性，支链或环状烷基，可以具有取代基，具有2到10个碳原子的线性，支链或环状烯基，可以具有取代基，或类似物，R1和R2可以连接形成>C═O基团，同时与它们附着的碳原子，R3和R4可以连接形成>C═O基团，同时与它们附着的碳原子，R5和R6可以连接形成>C═O基团，同时与它们附着的碳原子，或者R1，R2，R3，R4，R5和R6中的任意两个可以连接形成具有1到4个碳原子的聚亚甲基基团，可以具有取代基。
• N-TERT-BUTOXYCARBONYL-2-PYRROLIDINONES AND PRODUCTION METHOD THEREOF
  申请人：Hirata Norihiko

  公开号：US20090163722A1

  公开（公告）日：2009-06-25

  N-tert-butoxycarbonyl-2-pyrrolidinones represented by the following formula (1). In the formula (1), R1, R2, R3, R4, R5 and R6 independently represent a hydrogen atom, a halogen atom, a cyano group, a linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, which may have a substituent, a linear, branched or cyclic alkenyl group having 2 to 10 carbon atoms, which may have a substituent, or the like, R1 and R2 may be linked to form a >C═O group along with the carbon atom to which both are attached, R3 and R4 may be linked to form a >C═O group along with the carbon atom to which both are attached, R5 and R6 may be linked to form a >C═O group along with the carbon atom to which both are attached, or any two among R1, R2, R3, R4, R5 and R6 may be linked to form a polymethylene group having 1 to 4 carbon atoms which may have a substituent.

  下列化学式（1）代表的是N-叔丁氧羰基-2-吡咯酮。 在化学式（1）中，R1、R2、R3、R4、R5和R6各自独立地代表氢原子、卤素原子、氰基、具有1到10个碳原子的直链、支链或环状烷基，可能具有取代基，具有2到10个碳原子的直链、支链或环状烯基，可能具有取代基，或者类似物。R1和R2可以连接形成>C═O基团，同时与两者连接的碳原子相连。R3和R4可以连接形成>C═O基团，同时与两者连接的碳原子相连。R5和R6可以连接形成>C═O基团，同时与两者连接的碳原子相连。或者，在R1、R2、R3、R4、R5和R6中的任意两个可以连接形成具有1到4个碳原子的聚亚甲基基团，可能具有取代基。
• Process for preparing optically active 4-hydroxy-2-pyrrolidinone and N-substituted 4-hydroxy-2-pyrrolidinones by enzymatic hydroxylation
  申请人：Eidgenössische Technische Hochschule Zürich

  公开号：EP1197561A1

  公开（公告）日：2002-04-17

  This invention provides a process for the preparation of optically active 4-hydroxy-2-pyrrolidinone or N-substituted 4-hydroxy-2-pyrrolidinones, wherein an oxygen atom is inserted regio- and stereoselectively into the corresponding non-hydroxylated 2-pyrrolidinones, by using, as a biocatalyst, a microorganism having hydroxylation activity, or a host-organism having the gene(s) necessary for the hydroxylation enzymes derived from the said microorganism, or an enzyme having hydroxylation activity derived from the above microorganisms. The microorganism may be selected from the group consisting of microorganisms that degrade alkanes or cyclic hydrocarbons, microorganisms having alkane hydroxylase(s), or microorganisms that are able to oxidize hydrocarbons.

  本发明提供了一种制备具有光学活性的 4-羟基-2-吡咯烷酮或 N-取代的 4-羟基-2-吡咯烷酮的工艺，其中氧原子可在相应的非羟基化 2-吡咯烷酮中进行区域和立体选择性插入、作为生物催化剂，使用具有羟基化活性的微生物，或具有羟基化酶所需基因的宿主生物，或从上述微生物中提取的具有羟基化活性的酶。所述微生物可选自降解烷烃或环烃的微生物、具有烷烃羟化酶的微生物或能够氧化烃的微生物。