(1R,5S)-3-tert-butoxycarbonyl-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2-one | 955389-15-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1R,5S)-3-tert-butoxycarbonyl-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2-one
• 英文别名: tert-butyl (1R,5S)-6,6-dimethyl-2-oxo-3-azabicyclo[3.1.0]hexane-3-carboxylate
• CAS: 955389-15-8
• 化学式: C₁₂H₁₉NO₃
• 分子量: 225.288
• InChiKey: RJZCARKCRNCPGY-YUMQZZPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,5S)-3-tert-butoxycarbonyl-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2-one 在 二异丁基氢化铝 、 sodium hydroxide 、 水 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 以95.5%的产率得到(1R,5S)-3-tert-butoxycarbonyl-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2-ol
  参考文献：
  名称：

  EP2014648

  摘要：

  公开号：
• 作为产物：
  描述：

  (1R,5S)-6,6-二甲基-3-氮杂双环[3.1.0]己烷-2-酮 、 二碳酸二叔丁酯 在 4-二甲氨基吡啶 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以78.8%的产率得到(1R,5S)-3-tert-butoxycarbonyl-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2-one
  参考文献：
  名称：

  N-TERT-BUTOXYCARBONYL-2-PYRROLIDINONE AND PROCESS FOR PRODUCING THE SAME

  摘要：

  公开号：

  EP2008999B1

文献信息

• METHOD OF PRODUCING POLYCYCLIC PROLINE DERIVATIVE OR ACID ADDITION SALT THEREOF
  申请人：Hirata Norihiko

  公开号：US20090281331A1

  公开（公告）日：2009-11-12

  A process for producing proline derivatives of formula (1) below or acid adduct salts thereof, including: the step of reacting N-protected pyrrolidinones of formula (2) below with reducing agents to thereby obtain N-protected pyrrolidinols of formula (3) below (step A); the step of reacting the N-protected pyrrolidinols obtained in the step A with cyanating agents to thereby obtain N-protected cyanopyrrolidines of formula (4) below (step B); the step of reacting the N-protected cyanopyrrolidines obtained in the step B with alcohols and bases to thereby obtain imidates of formula (5) below and treating the imidates with acids to thereby obtain N-protected prolines of formula (6) below (step C); and the step of treating the N-protected prolines obtained in the step C with acids (step D). In formulas (1)-(6) below, any two out of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are bonded with each other to thereby form an optionally substituted C 1 -C 4 polymethylene; and R 7 is an optionally substituted C 1 -C 10 linear alkyl, etc.

  以下是生产公式（1）的脯氨酸衍生物或其酸加合物的过程，包括：将公式（2）的N-保护吡咯烷酮与还原剂反应以获得公式（3）的N-保护吡咯烷醇（步骤A）；将步骤A中获得的N-保护吡咯烷醇与氰化剂反应以获得公式（4）的N-保护氰基吡咯烷（步骤B）；将步骤B中获得的N-保护氰基吡咯烷与醇和碱反应以获得公式（5）的咪唑酯，并用酸处理咪唑酯以获得公式（6）的N-保护脯氨酸（步骤C）；将步骤C中获得的N-保护脯氨酸用酸处理（步骤D）。在下面的公式（1）-（6）中，R1，R2，R3，R4，R5和R6中的任意两个可以彼此结合以形成可选的取代C1-C4聚亚甲基；而R7是可选的取代C1-C10线性烷基等。
• 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。
• N-TERT-BUTOXYCARBONYL-2-PYRROLIDINONES AND PROCESS FOR PRODUCING THE SAME
  申请人：Sumitomo Chemical Company, Limited

  公开号：EP2008999A1

  公开（公告）日：2008-12-31

  N-tert-butoxycarbonyl-2-pyrrolidinones of the following formula (1): [wherein, R1, R2, R3, R4, R5 and R6 represent each independently a hydrogen atom, halogen atom, cyano group, optionally substituted linear, branched or cyclic alkyl group having 1 to 10 carbon atoms, optionally substituted linear, branched or cyclic alkenyl group having 2 to 10 carbon atoms, optionally substituted aryl group having 6 to 20 carbon atoms, optionally substituted amino group, -ORa group, or -SRb group, Ra and Rb represent each independently a hydrogen atom, alkylcarbonyl group having 2 to 10 carbon atoms, arylcarbonyl group having 7 to 20 carbon atoms, aralkyl group having 7 to 20 carbon atoms, alkoxyalkyl group having 2 to 10 carbon atoms, trialkylsilyl group having 3 to 10 carbon atoms, alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 20 carbon atoms, alternatively, R1 and R2 may be connected to form a >C=O group together with a carbon atom to which they are connected, R3 and R4 may be connected to form a >C=O group together with a carbon atom to which they are connected, R5 and R6 may be connected to form a >C=O group together with a carbon atom to which they are connected, any two of R1, R2, R3, R4, R5 and R6 may be connected to form an optionally substituted polymethylene group having 1 to 4 carbon atoms, one or no-mutually-adjacent two methylene groups constituting the polymethylene group may be substituted by an oxygen atom, one or two ethylene groups constituting the polymethylene group may be substituted by a vinylene group, no-mutually-adjacent two methylene groups constituting the polymethylene group may be mutually connected via an oxygen atom, methylene group, ethylene group or vinylene group.].

  下式(1)的 N-叔丁氧羰基-2-吡咯烷酮： [其中，R1、R2、R3、R4、R5 和 R6 各自独立地代表氢原子、卤素原子、氰基、任选取代的具有 1 至 10 个碳原子的直链、支链或环状烷基、任选取代的具有 2 至 10 个碳原子的直链、支链或环状烯基、任选取代的具有 6 至 20 个碳原子的芳基、任选取代的氨基、-Ra和 Rb 各自独立地代表氢原子、具有 2 至 10 个碳原子的烷基羰基、具有 7 至 20 个碳原子的芳基羰基、具有 7 至 20 个碳原子的芳烷基、具有 2 至 10 个碳原子的烷氧基烷基、具有 3 至 10 个碳原子的三烷基硅基、具有 1 至 10 个碳原子的烷基、具有 6 至 20 个碳原子的芳基、 或者，R1 和 R2 连接在一起，形成一个 >C=O 基团，R3 和 R4 连接在一起，形成一个 >C=O 基团，R5 和 R6 连接在一起，形成一个 >C=O 基团，R7 和 R8 连接在一起，形成一个 >C=O 基团，R8 和 R9 连接在一起，形成一个 >C=O 基团，R1 和 R2 连接在一起，形成一个 >C=O 基团，R3 和 R4 连接在一起，形成一个 >C=O 基团，R5 和 R6 连接在一起，形成一个 >C=O 基团、 R1、R2、R3、R4、R5 和 R6 中的任意两个可连接成具有 1 至 4 个碳原子的任选取代的聚亚甲基，构成聚亚甲基的一个或不相邻的两个亚甲基可被一个氧原子取代、构成聚亚甲基的一个或两个亚乙基基团可被亚乙烯基团取代，构成聚亚甲基的不相邻的两个亚甲基基团可通过氧原子、亚甲基基团、亚乙基基团或亚乙烯基团相互连接。].
• PROCESS FOR PRODUCING POLYCYCLIC PROLINE DERIVATIVE OR ACID ADDUCT SALT THEREOF
  申请人：Sumitomo Chemical Company, Limited

  公开号：EP2014648A1

  公开（公告）日：2009-01-14

  A method of producing a proline derivative of the following formula (1) or an acid addition salt thereof, comprising the following four steps A to D: [wherein, any two of R1, R2, R3, R4, R5 and R6 are connected to form an optionally substituted polymethylene group having 1 to 4 carbon atoms, and R7 represents an optionally substituted linear alkyl group having 1 to 10 carbon atoms, branched alkyl group having 2 to 10 carbon atoms, linear alkenyl group having 2 to 10 carbon atoms, branched alkenyl group having 3 to 10 carbon atoms or aralkyl group having 7 to 20 carbon atoms.] (Step A) A step of reacting N-protected pyrrolidinones of the following formula (2) with a reducing agent, to produce N-protected pyrrolidinols of the following formula (3): (Step B) A step of reacting the N-protected pyrrolidinols of the formula (3) obtained in the step A with a cyanodizing agent, to produce N-protected cyanopyrrolidines of the following formula (4): (Step C) A step of reacting the N-protected cyanopyrrolidines of the formula (4) obtained in the step B with alcohols and a base, to obtain imidates of the following formula (5), and treating the imidates with an acid, to produce N-protected prolines of the following formula (6): (Step D) A step of treating the N-protected prolines of the formula (6) obtained in the step C with an acid, to produce a proline derivative of the above-described formula (1) or an acid addition salt thereof.

  一种生产下式（1）的脯氨酸衍生物或其酸加成盐的方法，包括以下四个步骤 A 至 D： [其中，R1、R2、R3、R4、R5 和 R6 中的任意两个连接形成具有 1 至 4 个碳原子的任选取代的聚亚甲基，R7 代表具有 1 至 10 个碳原子的任选取代的直链烷基、具有 2 至 10 个碳原子的支链烷基、具有 2 至 10 个碳原子的直链烯基、具有 3 至 10 个碳原子的支链烯基或具有 7 至 20 个碳原子的芳烷基。］ (步骤 A） 将下式（2）的 N-保护吡咯烷酮与还原剂反应，生成下式（3）的 N-保护吡咯烷 醇： (步骤 B） 将步骤 A 中得到的式 (3) 的 N-保护吡咯烷酮与氰化剂反应，生成下式 (4) 的 N-保护氰基吡咯烷： (步骤 C） 将步骤 B 中得到的式 (4) 的 N-保护氰基吡咯烷与醇和碱反应，得到下式 (5) 的亚胺酸盐，并用酸处理亚胺酸盐，得到下式 (6) 的 N-保护脯氨酸： (步骤 D） 用酸处理步骤 C 中得到的式 (6) 的 N-保护脯氨酸，生成上述式 (1) 的脯氨酸衍生物或其酸加成盐。