N-{(1S)-1-[(3R)-1-benzylpyrrolidin-3-yl]ethyl}-N-methylamine | 161011-00-3

• 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: N-{(1S)-1-[(3R)-1-benzylpyrrolidin-3-yl]ethyl}-N-methylamine
• 英文别名: (3R,1'S)-1-benzyl-3-[(1'-N-methylamino)ethyl]pyrrolidine；(R,S)-1-benzyl-3-[1'-(methylamino)ethyl]pyrrolidine；(1S)-1-[(3R)-1-benzylpyrrolidin-3-yl]-N-methylethanamine
• CAS: 161011-00-3
• 化学式: C₁₄H₂₂N₂
• 分子量: 218.342
• InChiKey: VVOUASUWFMGGHV-GXTWGEPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-{(1S)-1-[(3R)-1-benzylpyrrolidin-3-yl]ethyl}-N-methylamine 在 20% palladium hydroxide-activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 25.0~30.0 ℃ 、1.01 MPa 条件下， 反应 48.0h， 以85%的产率得到3R-(1S-N-methylaminoethyl)pirrolidine
  参考文献：
  名称：

  外消旋β-酮内酰胺在铱催化下的动态动力学拆分

  摘要：

  已经描述了通过动态动力学拆分（DKR）的高效Ir催化的外消旋β-酮内酰胺的不对称氢化，用于合成光学活性的β-羟基内酰胺。使用Ir-SpiroSAP催化剂，可将一系列外消旋的β-酮内酰胺（包括β-酮γ-，δ-和ε-内酰胺）以高收率（87-99％）氢化成手性β-羟基内酰胺，同时具有出色的对映体性能。在温和的反应条件下，在低催化剂负载下的非对映选择性（83–99.9％ee，顺/反：97：3–> 99：1）。该有效方法已成功地用于氟喹诺酮类抗生素前马氟沙星的手性中间体的合成。

  DOI：

  10.1021/acs.orglett.6b03397
• 作为产物：
  描述：

  methyl (3S)-3-{[(benzyloxy)carbonyl]amino}butanoate 在 lithium aluminium tetrahydride 、 正丁基锂 、 臭氧 、 二异丙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 116.67h， 生成 N-{(1S)-1-[(3R)-1-benzylpyrrolidin-3-yl]ethyl}-N-methylamine
  参考文献：
  名称：

  Synthesis of N-Methyl-N-{(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl}amine

  摘要：

  N-Methyl-N-{(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl}amine (1)(1) is a key intermediate in the preparation of premafloxacin (2), which was under development as an antibiotic for use against pathogens of veterinary importance. This paper describes the development of a practical, efficient, and stereoselective process for the preparation of 1 from isobutyl (3S)-3-{methyl[(1S)-1-phenylethyl]amino}butanoate (5c). The key steps in the synthetic sequence are an asymmetric Michael addition, which yields 5c, and a stereoselective alkylation, which yields (3S,4S)-3-allyl-1,4-dimethylazetidin-2-one (17).

  DOI：

  10.1021/jo0349633

文献信息

• Optically active 3-(1-(alkylamino))alkyl pyrrolidines
  申请人：Pharmacia & Upjohn Company

  公开号：US05773610A1

  公开（公告）日：1998-06-30

  This invention relates to processes for the synthesis of various optically active amino pyrrolidinyl stereoisomers, or enantiomers, that may be attached to quinolonecarboxylic acids or naphthyridones. Processes and essential intermediates are disclosed and claimed for the synthesis of compounds represented by the structure shown in FIG. BG.sub.4-1, where R.sup.50, R.sup.6 and R.sup.9 are defined independently and are H, -(C.sub.1 -C.sub.8)alkyl, -(C.sub.3 -C.sub.8)cycloalkyl, -(C.sub.1 -C.sub.8)alkyl-(C.sub.3 -C.sub.8)cycloalkyl, -(C.sub.6 -C.sub.12 aryl), -(C.sub.1 -C.sub.8)alkyl-(C.sub.6 -C.sub.12 aryl), or the aryl or alkyl is substituted with one to three of the following groups, (C.sub.6 -C.sub.12 aryl), (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, halogen, trifluoromethyl; where R.sup.2 is -(C.sub.1 -C.sub.8)alkyl, -(C.sub.3 -C.sub.8)cycloalkyl, -(C.sub.1 -C.sub.8)alkyl-(C.sub.3 -C.sub.8)cycloalkyl, -(C.sub.6 -C.sub.12 aryl), -(C.sub.1 -C.sub.8)alkyl-(C.sub.6 -C.sub.12 aryl), or the aryl or alkyl is substituted with one to three of the following groups, -(C.sub.6 -C.sub.12 aryl), -(C.sub.1 -C.sub.3)alkyl,-(C.sub.1 -C.sub.3)alkoxy, halogen, trifluoromethyl; depending upon the starting materials used, compounds represented by the structure shown by FIG. BG.sub.4-1 may have one of either of the two stereochemical arrangements shown, or, if the starting materials are a racemic mixture, the reaction may produce a 1:1 ratio of the combination of products shown in FIG. BG.sub.4-1, i.e. a racemic mixture.

  本发明涉及合成各种光学活性氨基吡咯烷基立体异构体或对喹啉羧酸或萘啉酮的合成过程。揭示和声明了用于合成由图BG.sub.4-1所示结构表示的化合物的过程和必要中间体，其中R.sup.50、R.sup.6和R.sup.9分别定义并且是H、-(C.sub.1-C.sub.8)烷基、-(C.sub.3-C.sub.8)环烷基、-(C.sub.1-C.sub.8)烷基-(C.sub.3-C.sub.8)环烷基、-(C.sub.6-C.sub.12芳基)、-(C.sub.1-C.sub.8)烷基-(C.sub.6-C.sub.12芳基)，或芳基或烷基被以下一到三个基团取代：(C.sub.6-C.sub.12芳基)、(C.sub.1-C.sub.3)烷基、(C.sub.1-C.sub.3)烷氧基、卤素、三氟甲基；其中R.sup.2是-(C.sub.1-C.sub.8)烷基、-(C.sub.3-C.sub.8)环烷基、-(C.sub.1-C.sub.8)烷基-(C.sub.3-C.sub.8)环烷基、-(C.sub.6-C.sub.12芳基)、-(C.sub.1-C.sub.8)烷基-(C.sub.6-C.sub.12芳基)，或芳基或烷基被以下一到三个基团取代：-(C.sub.6-C.sub.12芳基)、-(C.sub.1-C.sub.3)烷基、-(C.sub.1-C.sub.3)烷氧基、卤素、三氟甲基；根据所使用的起始材料，由图BG.sub.4-1所示结构表示的化合物可能具有所示的两种立体化学排列中的其中一种，或者如果起始材料是外消旋混合物，则反应可能产生1:1的图BG.sub.4-1所示产物组合的比例，即外消旋混合物。
• Optically active 3-(1-(carbamoyl))alkyl-2-oxo-pyrrolidines and optically
  申请人：Pharmacia & Upjohn Company

  公开号：US06140510A1

  公开（公告）日：2000-10-31

  This invention relates to processes for the synthesis of various optically active amino pyrrolidinyl stereoisomers, or enantiomers, that may be attached to quinolonecarboxylic acids or naphthyridones. Processes and essential intermediates are disclosed and claimed for the synthesis of compounds represented by the structure shown in figure BG.sub.4-1, below. ##STR1## where R.sup.50, R.sup.6 and R.sup.9 are defined independently and are H, --(C.sub.1 -C.sub.8)alkyl, --(C.sub.3 -C.sub.8)cycloalkyl, --(C.sub.1 -C.sub.8)alkyl-(C.sub.3 -C.sub.8)cycloalkyl, --(C.sub.6 -C.sub.12 aryl), --(C.sub.1 -C.sub.8)alkyl-(C.sub.6 -C.sub.12 aryl), or the aryl or alkyl is substituted with one to three of the following groups, (C.sub.6 -C.sub.12 aryl), (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3) alkoxy, halogen, trifluoromethyl; where R.sup.2 is --(C.sub.1 -C.sub.8)alkyl, --(C.sub.3 -C.sub.8)cycloalkyl, --(C.sub.1 -C.sub.8)alkyl-(C.sub.3 -C.sub.8)cycloalkyl, --(C.sub.6 -C.sub.12 aryl), --(C.sub.1 -C.sub.8)alkyl-(C.sub.6 -C.sub.12 aryl), or the aryl or alkyl is substituted with one to three of the following groups, --(C.sub.6 -C.sub.12 aryl), --(C.sub.1 -C.sub.3)alkyl, --(C.sub.1 -C.sub.3) alkoxy, halogen, trifluoromethyl; depending upon the starting materials used, compounds represented by the structure shown by figure BG.sub.4-1 may have one of either of the two steriochemical arrangments shown, or, if the starting materials are a racemic mixture, the reaction may produce a 1:1 ratio of the combination of products shown in Figure BG.sub.4-1, i.e. a racemic mixture.

  本发明涉及合成各种光学活性氨基吡咯烷基立体异构体或对喹啉羧酸或萘啉酮的合成过程。本发明揭示和声明了合成由下图BG.sub.4-1所示结构代表的化合物的过程和必要的中间体。其中，R.sup.50，R.sup.6和R.sup.9分别定义为H，-(C.sub.1-C.sub.8)烷基，-(C.sub.3-C.sub.8)环烷基，-(C.sub.1-C.sub.8)烷基-(C.sub.3-C.sub.8)环烷基，-(C.sub.6-C.sub.12芳基)，-(C.sub.1-C.sub.8)烷基-(C.sub.6-C.sub.12芳基)，或芳基或烷基被以下一到三种基团之一取代：(C.sub.6-C.sub.12芳基)，(C.sub.1-C.sub.3)烷基，(C.sub.1-C.sub.3)氧代烷基，卤素，三氟甲基；其中，R.sup.2为-(C.sub.1-C.sub.8)烷基，-(C.sub.3-C.sub.8)环烷基，-(C.sub.1-C.sub.8)烷基-(C.sub.3-C.sub.8)环烷基，-(C.sub.6-C.sub.12芳基)，-(C.sub.1-C.sub.8)烷基-(C.sub.6-C.sub.12芳基)，或芳基或烷基被以下一到三种基团之一取代：-(C.sub.6-C.sub.12芳基)，-(C.sub.1-C.sub.3)烷基，-(C.sub.1-C.sub.3)氧代烷基，卤素，三氟甲基；根据所使用的起始材料，由图BG.sub.4-1所示结构表示的化合物可能具有所示的两种立体化学排列中的任意一种，或者，如果起始材料是一个外消旋混合物，则反应可能产生图BG.sub.4-1所示的产品组合的1:1比例，即一个外消旋混合物。
• A process for producing optically active pyrrolidine derivatives
  申请人：Takasago International Corporation

  公开号：EP0855390B1

  公开（公告）日：2001-10-04
• US5942629A
  申请人：——

  公开号：US5942629A

  公开（公告）日：1999-08-24
• [EN] OPTICALLY ACTIVE 3-(1-(ALKYLAMINO))ALKYL PYRROLIDINES<br/>[FR] 3-(1-(ALKYLAMINO))ALKYL PYRROLIDINES OPTIQUEMENT ACTIVES
  申请人：THE UPJOHN COMPANY

  公开号：WO1994026708A1

  公开（公告）日：1994-11-24

  (EN) This invention relates to processes for the synthesis of various optically active amino pyrrolidinyl stereoisomers, or enantiomers, that may be attached to quinolonecarboxylic acids or naphthyridones. Processes and essential intermediates are disclosed and claimed for the synthesis of compounds represented by the structure shown in figure BG4-1, where R50, R6 and R9 are defined independently and are H, --(C1-C8)alkyl, --(C3-C8)cycloalkyl, --(C1-C8)alkyl-(C3-C8)cycloalkyl, --(C6-C12 aryl), --(C1-C8)alkyl-(C6-C12 aryl), or the aryl or alkyl is substituted with one to three of the following groups, (C6-C12 aryl), (C1-C3)alkyl, (C1-C3)alkoxy, halogen, trifluoromethyl; where R2 is --(C1-C8)alkyl, --(C3-C8)cycloalkyl, --(C1-C8)alkyl-(C3-C8)cycloalkyl, --(C6-C12 aryl), --(C1-C8)alkyl-(C6-C12 aryl), or the aryl or alkyl is substituted with one to three of the following groups, --(C6-C12 aryl), --(C1-C3)alkyl, --(C1-C3)alkoxy, halogen, trifluoromethyl; depending upon the starting materials used, compounds represented by the structure shown by figure BG4-1 may have one of either of the two stereochemical arrangements shown, or, if the starting materials are a racemic mixture, the reaction may produce a 1:1 ratio of the combination of products shown in figure BG4-1, i.e. a racemic mixture.(FR) La présente invention concerne des procédés pour la synthèse de divers stéréoisomères ou énantiomères d'amino pyrrolidinyle optiquement actifs, qui peuvent être accolés à des acides quinolonecarboxyliques ou des naphtyridones. Des procédés et des intermédiaires essentiels sont décrits et revendiqués pour la synthèse de composés représentés par la structure reproduite à la figure BG4-1, où R50, R6 et R9 sont définis indépendamment et sont H, --alkyl(C1-C8), --cycloalkyl(C3-C8), --alkyl(C1-C8), cycloalkyl(C3-C8), --(aryl C6-C12), --alkyl(C1-C8), -(aryl C6-C12), ou bien l'aryle ou l'alkyle est substitué avec un à trois des groupes suivants, (aryl C6-C12), alkyl(C1-C3), alcoxy(C1-C3), halogène, trifluorométhyle; où R2 est --alkyl(C1-C8), --cycloalkyl(C3-C8), --alkyl(C1-C8), -cycloalkyl(C3-C8), --(aryl C6-C12), --alkyl(C1-C8), -(aryl C6-C12), ou bien l'aryle ou l'alkyle est substitué avec un à trois des groupes suivants, --(aryl C6-C12), --alkyl(C1-C3), --alcoxy(C1-C3), halogène, trifluorométhyle, en fonction des produits de départ utilisés, les composés représentés par la structure reproduite à la figure BG4-1 peuvent présenter l'une ou l'autre des deux dispositions stéréochimiques reproduites, ou bien, si les produits de départ sont un mélange racémique, la réaction peut donner un rapport 1:1 de la combinaison de produits représentée à la figure BG4-1, c'est-à-dire un mélange racémique.