(+/-)-erythro-methyl 2-phenyl-2-(2-azacyclopentyl)acetate

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (+/-)-erythro-methyl 2-phenyl-2-(2-azacyclopentyl)acetate
• 英文别名: methyl (R*)-2-phenyl-2-((S*)-pyrrolidin-2-yl)acetate；methyl phenyl(pyrrolidin-2-yl)acetate；methyl (2S)-2-phenyl-2-[(2R)-pyrrolidin-2-yl]acetate
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: IDFZQTFWJZUVDF-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  三氟乙酸酐 、 (+/-)-erythro-methyl 2-phenyl-2-(2-azacyclopentyl)acetate 以 二氯甲烷 为溶剂， 生成 (S)-Phenyl-[(R)-1-(2,2,2-trifluoro-acetyl)-pyrrolidin-2-yl]-acetic acid methyl ester
  参考文献：
  名称：

  有机合成的新战略反应：催化不对称 C−H 活化 α 到氮作为曼尼希反应的替代品

  摘要：

  重氮乙酸甲酯的不对称 CH 活化反应很容易被脯氨酸铑催化剂 Rh(2)(S-DOSP)(4) (1) 或桥连脯氨酸催化剂 Rh(2)(S-biDOSP)(2) (2a) 诱导) 和 Rh(2)(S-biTISP)(2) (2b)。N-Boc 保护的环胺的 CH 活化表明供体/受体取代的类卡宾显示出显着的化学选择性，可以实现高度区域选择性、非对映选择性和对映选择性反应。此外，这些反应可以显示出高水平的双立体分化和动力学分辨率。CH 活化是由铑卡宾诱导的 CH 插入引起的。这种化学反应的潜力可以通过非常直接地合成哌醋甲酯来证明。

  DOI：

  10.1021/ja0290072
• 作为产物：
  描述：

  α-溴苯乙酸甲酯 在 platinum(IV) oxide 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 生成 (+/-)-erythro-methyl 2-phenyl-2-(2-azacyclopentyl)acetate
  参考文献：
  名称：

  The influence of the ring size of thiolactams in the Eschenmoser coupling reaction in presence of DBU. Formation of bicyclic thiazolidinones or thioimines

  摘要：

  The different behaviors of pyrrolidin-2-thione and piperidin-2-thione under a modified Eschenmoser sulfur contraction reaction protocol using DBU as base was observed. The pyrrolidin-2-thione lb follows the expected reaction course, leading to thioimines 5a-d. which can be transformed subsequently into the respective by action of a thiophile, while the piperidin-2-thione leads to the formation of bicyclic thiazolidinones 4b-d in moderate to good yields. The -enaminocarbonyl compound 11 was hydrogenated to afford the respective five-membered analogue of methylphenidate 12. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.12.049

文献信息

• Potassium channel inhibitors
  申请人：Bilodeau T. Mark

  公开号：US20060030595A1

  公开（公告）日：2006-02-09

  The present invention relates to compounds having the structure useful as potassium channel inhibitors to treat cardiac arrhythmias, and the like.

  这项发明涉及具有结构的化合物，可用作钾通道抑制剂，用于治疗心律失常等疾病。
• α-C–H Bond Functionalization of Unprotected Alicyclic Amines: Lewis-Acid-Promoted Addition of Enolates to Transient Imines
  作者：Jae Hyun Kim、Anirudra Paul、Ion Ghiviriga、Daniel Seidel

  DOI：10.1021/acs.orglett.0c04024

  日期：2021.2.5

  lithium amides by oxidation with simple ketone oxidants, are readily alkylated with a range of enolates to provide mono- and polycyclic β-aminoketones in a single operation, including the natural product (±)-myrtine. Nitrile anions also serve as competent nucleophiles in these transformations, which are promoted by BF3 etherate. β-Aminoesters derived from ester enolates can be converted to the corresponding

  可烯醇化的环状亚胺是通过用简单的酮氧化剂氧化从相应的氨基锂原位获得的，很容易用一系列烯醇化物烷基化，在一次操作中提供单环和多环 β-氨基酮，包括天然产物 (±)-肉豆蔻碱。腈阴离子也在这些转化中充当有效的亲核试剂，BF 3醚化物促进了这些转化。源自酯烯醇化物的β-氨基酯可以转化为相应的β-内酰胺。
• Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new synthetic methodology for methylphenidate analogs based on the Blaise reaction
  作者：H Deutsch

  DOI：10.1016/s0223-5234(01)01230-2

  日期：2001.4

  uptake using rat striatal tissue. When the heterocyclic ring size was varied, the six-membered ring of methylphenidate appeared to be the optimum ring size. When the aryl ring was varied the 4-trifluoromethylphenyl analog was less potent than methylphenidate, the beta-naphthyl congener was considerably more potent, whereas the alpha-naphthyl congener was less potent. Most of the compounds tested had ratios

  为了制备多巴胺（DA）摄取抑制剂哌醋甲酯的新类似物，开发了一种基于Blaise反应的合成方法。α-溴苯基乙酸酯，锌和α-氰基-ω-甲磺酸酯之间的反应可得到稳定的伯烯胺。用氰基硼氢化物还原烯胺后，可以将胺环化成哌醋甲酯类似物，其中胺环的大小和芳环是变化的。使用大鼠纹状体组织测试了这些化合物对[[3] H] WIN 35,428与可卡因识别位点的结合的抑制作用和[[3] H] DA的吸收。当杂环大小变化时，哌醋甲酯的六元环似乎是最佳的环大小。当芳基环发生变化时，4-三氟甲基苯基类似物的效力不及哌醋甲酯。β-萘同源物的效力明显更高，而α-萘同源物的效力更低。所测试的大多数化合物具有与可卡因相似的摄取与结合抑制之比（区分比），因此不是开发可卡因拮抗剂的先导化合物。
• Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites
  作者：Huw M.L. Davies、Darrin W. Hopper、Tore Hansen、Quixu Liu、Steven R. Childers

  DOI：10.1016/j.bmcl.2003.12.097

  日期：2004.4

  acid is a very direct method for the synthesis of methylphenidate analogues. By using either dirhodium tetraacetate or dirhodium tetraprolinate derivatives as catalyst, either the racemic or enantioenriched methylphenidate analogues can be prepared. The binding affinities of the methylphenidate analogues to both the dopamine and the serotonin transporters are described. The most notable compounds are the

  用N-Boc-哌啶或N-Boc-吡咯烷进行铑（II）催化的分子间CH插入芳基重氮乙酸甲酯，然后用三氟乙酸脱保护是合成哌醋甲酯类似物的非常直接的方法。通过使用四乙酸二钠吡啶鎓或四脯氨酸四氢吡啶鎓衍生物作为催化剂，可以制备外消旋的或对映体富集的哌醋甲酯类似物。描述了哌醋甲酯类似物与多巴胺和5-羟色胺转运蛋白的结合亲和力。最引人注目的化合物是对5-羟色胺转运蛋白具有高结合亲和力和选择性的赤型-（2-萘基）类似物。
• Studies on the Eschenmoser coupling reaction and insights on its mechanism. Application in the synthesis of Norallosedamine and other alkaloids
  作者：Brenno A.D. Neto、Alexandre A.M. Lapis、Alinne B. Bernd、Dennis Russowsky

  DOI：10.1016/j.tet.2009.01.081

  日期：2009.3

  The conditions of the Eschenmoser coupling reaction were studied. The formation of the alpha-thioiminium ion was achieved faster in the presence of an additive (Nal) and dry chloroform as the preferred solvent. The developed conditions were used for the second part of the reaction (the sulfur extrusion itself). The present protocol avoids the formation of byproducts, which were previously described as a major drawback to be overcome. Electrospray ionization tandem mass spectrometry was used to characterize some aspects (intermediates) of the first step of the reaction mechanism. Some reduction conditions were properly tested and the selected conditions were applied to the synthesis of the natural alkaloid Norallosedamine and other derivatives. (C) 2009 Elsevier Ltd. All rights reserved.