(R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoate | 1246400-77-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoate
• 英文别名: Methyl (R)-2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoate；methyl (2R)-3-(3,5-difluorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 1246400-77-0
• 化学式: C₁₅H₁₉F₂NO₄
• 分子量: 315.317
• InChiKey: NXXPORDSTWEDBN-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 Boc-D-3,5-二氟苯丙氨酸
  参考文献：
  名称：

  Discovery of pyrrolopyrimidine inhibitors of Akt

  摘要：

  The discovery and optimization of a series of pyrrolopyrimidine based protein kinase B (Pkb/Akt) inhibitors discovered via HTS and structure based drug design is reported. The compounds demonstrate potent inhibition of all three Akt isoforms and knockdown of phospho-PRAS40 levels in LNCaP cells and tumor xenografts. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.053
• 作为产物：
  描述：

  (Z)-methyl 2-(tert-butoxycarbonyl)amino-3-(3,5-difluorophenyl)acrylate 在 bis(norbornadiene)rhodium(l)tetrafluoroborate 、 C₆₀H₄₆O₄P₂ 、 氢气 作用下， 以 四氢呋喃 为溶剂， 20.0 ℃ 、2.0 MPa 条件下， 反应 18.0h， 生成 (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanoate
  参考文献：
  名称：

  Rh（P ？ OP）配合物催化的不对称加氢对映选择手性药物

  摘要：

  P  OP艺术：P的铑络合物 OP配体充当在不对称氢化作为高效和对映选择性的催化剂导致各种有价值的药物积木和手性药物如LY2497282，拉考沙胺，利凡斯的明，和阿瑞匹坦和12个进一步示例几个直接前体（参见方案; nbd =降冰片二烯; XC（O）G = NHAc，NHBoc，NHCbz，2-氧吡咯烷-1--1-基，OAc）。

  DOI：

  10.1002/chem.201103014

文献信息

• Chiral Rhodium Complexes Derived From Electron-Rich Phosphine-Phosphites as Asymmetric Hydrogenation Catalysts
  作者：Pablo Etayo、José L. Núñez-Rico、Anton Vidal-Ferran

  DOI：10.1021/om200933b

  日期：2011.12.26

  Two new chiral cationic rhodium(I) complexes derived from electron-rich dicyclohexylphosphine-phosphite ligands were prepared from enantiopure Sharpless epoxy ethers. The best-performing catalyst system, which bears a less bulky methyl ether moiety, exhibited remarkably high enantioselectivity (up to 99% ee) and reactivity (up to >2500 TON) in asymmetric hydrogenation reactions of various functionalized

  从对映体纯的Sharpless环氧醚中制备了两种新的手性阳离子铑（I）配合物，它们来自富含电子的二环己基膦-亚磷酸酯配体。性能最佳的催化剂体系，具有较小的甲基醚部分，在各种官能化烯烃（α-（酰氨基））的不对称加氢反应中表现出极高的对映选择性（高达99％ee）和反应性（高达> 2500 TON）。丙烯酸酯，衣康酸衍生物，α-取代的烯醇酯和α-芳基酰胺）。我们的合成方法已成功应用于抗癫痫药（R）-乳糖酰胺（Vimpat）的对映选择性合成。
• Highly Modular POP Ligands for Asymmetric Hydrogenation: Synthesis, Catalytic Activity, and Mechanism
  作者：Héctor Fernández-Pérez、Steven M. A. Donald、Ian J. Munslow、Jordi Benet-Buchholz、Feliu Maseras、Anton Vidal-Ferran

  DOI：10.1002/chem.200902915

  日期：2010.6.11

  pure POP ligands (phosphine–phosphite), straightforwardly available in two synthetic steps from enantiopure Sharpless epoxy ethers is reported. Both the alkyloxy and phosphite groups can be optimized for maximum enantioselectivity and catalytic activity. Their excellent performance in the Rh‐catalyzed asymmetric hydrogenation of a wide variety of functionalized alkenes (26 examples) and modular design

  据报道，有一个对映体纯的POP配体（膦-亚磷酸酯）库，可通过对映纯的Sharpless环氧醚在两个合成步骤中直接获得。烷氧基和亚磷酸酯基团均可被优化以实现最大的对映选择性和催化活性。它们在Rh催化的各种官能化烯烃的不对称氢化反应中的优异性能（26个实例）和模块化设计使其对于将来的应用具有吸引力。引线催化剂结合有（小号）-BINOL衍生（BINOL = 1,1'-联-2-萘酚）酯组计算研究揭示了该部分具有对我们的P的行为具有双重作用OP配体。一方面，亚磷酸酯的电子性质阻碍了四种可能的歧管中的两种中的底物的结合和反应。另一方面，BINOL的空间效应可以区分其余两个歧管，从而阐明了这些催化剂的高效率。
• P-Stereogenic <i>N</i>-Phosphine–Phosphite Ligands for the Rh-Catalyzed Hydrogenation of Olefins
  作者：Maria Biosca、Pol de la Cruz-Sánchez、Oscar Pàmies、Montserrat Diéguez

  DOI：10.1021/acs.joc.9b03508

  日期：2020.4.3

  We have identified a successful family of simple P-stereogenic N-phosphine-phosphite ligands for the Rh-catalyzed asymmetric hydrogenation of olefins. These catalysts show excellent enantiocontrol for alpha-dehydroamino acid derivatives and aenamides (ee's up to >99%) and promising results for the more challenging beta-analogues (ee's up to 80%). The usefulness of these catalytic systems was further demonstrated with the synthesis of several valuable precursors for pharmacologically active compounds, with ee's at least as high as the best ones reported previously (up to >99%).
• Enantioselective Access to Chiral Drugs by using Asymmetric Hydrogenation Catalyzed by Rh(POP) Complexes
  作者：Pablo Etayo、José Luis Núñez-Rico、Héctor Fernández-Pérez、Anton Vidal-Ferran

  DOI：10.1002/chem.201103014

  日期：2011.12.9

  POP art: Rhodium complexes of POP ligands serve as highly efficient and enantioselective catalysts in asymmetric hydrogenation leading to various valuable pharmaceutical building blocks and several direct precursors of chiral drugs such as LY2497282, lacosamide, rivastigmine, and aprepitant and 12 further examples (see scheme; nbd=norbornadiene; XC(O)G=NHAc, NHBoc, NHCbz, 2‐oxopyrrolidin‐1‐yl, OAc)

  P  OP艺术：P的铑络合物 OP配体充当在不对称氢化作为高效和对映选择性的催化剂导致各种有价值的药物积木和手性药物如LY2497282，拉考沙胺，利凡斯的明，和阿瑞匹坦和12个进一步示例几个直接前体（参见方案; nbd =降冰片二烯; XC（O）G = NHAc，NHBoc，NHCbz，2-氧吡咯烷-1--1-基，OAc）。
• Discovery of pyrrolopyrimidine inhibitors of Akt
  作者：James F. Blake、Nicholas C. Kallan、Dengming Xiao、Rui Xu、Josef R. Bencsik、Nicholas J. Skelton、Keith L. Spencer、Ian S. Mitchell、Richard D. Woessner、Susan L. Gloor、Tyler Risom、Stefan D. Gross、Matthew Martinson、Tony H. Morales、Guy P.A. Vigers、Barbara J. Brandhuber

  DOI：10.1016/j.bmcl.2010.08.053

  日期：2010.10

  The discovery and optimization of a series of pyrrolopyrimidine based protein kinase B (Pkb/Akt) inhibitors discovered via HTS and structure based drug design is reported. The compounds demonstrate potent inhibition of all three Akt isoforms and knockdown of phospho-PRAS40 levels in LNCaP cells and tumor xenografts. (C) 2010 Elsevier Ltd. All rights reserved.