(R)-3-(4-fluorophenyl)-glutaric acid monomethyl ester

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (R)-3-(4-fluorophenyl)-glutaric acid monomethyl ester
• 英文别名: methyl (R)-3-(4-fluorophenyl)glutarate；(R)-3-(4-fluorophenyl)-5-methoxy-5-oxopentanoic acid；(R)-3-(4-fluorophenyl)pentanedioic acid monomethyl ester；3S-(4-Fluoro-phenyl)-pentanedioic acid monomethyl ester；(3R)-3-(4-fluorophenyl)-5-methoxy-5-oxopentanoic acid
• 化学式: C₁₂H₁₃FO₄
• 分子量: 240.231
• InChiKey: YCDQTTZPMJRWCQ-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-3-(4-fluorophenyl)-glutaric acid monomethyl ester 在 溶剂黄146 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 水 为溶剂， 反应 10.75h， 生成 (S)-4-(4-fluorophenyl)-1-methyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  3,4-二氢吡啶-2-酮衍生物，P2X 7受体拮抗剂核心结构的中试制备

  摘要：

  描述了3和4的中试植物合成，这是一系列P2X 7拮抗剂的核心结构。二氢吡啶酮环中唯一的立体异构中心是通过催化去对称作用生成的。选择性的甲酰化，然后串联串联的内酰胺化/内酰胺化序列，产生了3,4-二氢吡啶-2--2-环。以多千克规模生产化合物3和4，具有良好的总收率（在六个步骤中为约22％）和优异的立体化学纯度（对于3，为97％ee，对于4，为100％ee ）。

  DOI：

  10.1021/op1000447
• 作为产物：
  描述：

  4-fluorochalcone 在 盐酸 、 potassium dihydrogenphosphate 、 氯化亚砜 、 5%-palladium/activated carbon 、 1-[3,5-bis(trifluoromethyl)phenyl]-3-[(1S,2R)-3-[tert-butyl(dimethyl)silyl]oxy-1-(dimethylamino)-1-(4-nitrophenyl)propan-2-yl]thiourea 、 氢气 、 sodium carbonate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 300.0h， 生成 (R)-3-(4-fluorophenyl)-glutaric acid monomethyl ester
  参考文献：
  名称：

  Chloramphenicol base chemistry. Part 11: 1 chloramphenicol base-derived thiourea-catalyzed enantioselective Michael addition of malononitrile to α , β -unsaturated ketones

  摘要：

  The first chloramphenicol base-derived thiourea-catalyzed enantioselective Michael addition of malononitrile to alpha,beta-unsaturated ketones is reported. The Michael adducts were obtained in good to excellent yields (up to 98% yield) and enantioselectivities (up to 94% ee). This reaction has a broad substrate scope to various alpha,beta-unsaturated ketones. With this in mind, this methodology was successfully applied to the synthesis of a chiral piperidone, an advanced building block for dihydropyridinone P2X(7) receptor antagonists. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2017.05.015

文献信息

• CINCHONA-BASED BIFUNCTIONAL ORGANOCATALYSTS AND METHOD FOR PREPARING CHIRAL HEMIESTERS USING THE SAME
  申请人：SONG Choong Eui

  公开号：US20110213151A1

  公开（公告）日：2011-09-01

  The present invention relates to cinchona-based bifunctional organocatalysts and methods for preparing chiral hemiesters using the same. More specifically, the present invention relates to methods for preparing chiral hemiesters from prochiral or meso cyclic acid anhydrides via desymmetrization, using bifunctional cinchona alkaloid catalysts comprising sulfonamide functional groups.

  本发明涉及基于金鸡纳碱的双功能有机催化剂以及利用其制备手性半酯的方法。更具体地，本发明涉及利用含有磺酰胺功能团的双功能金鸡纳碱生催化剂，通过非对称化从原消旋或中性环酸酐制备手性半酯的方法。
• Enantioselective Alcoholysis of meso-Glutaric Anhydrides Catalyzed by Cinchona-Based Sulfonamide Catalysts
  作者：Sang Eun Park、Eun Hye Nam、Hyeong Bin Jang、Joong Suk Oh、Surajit Some、Yong Seop Lee、Choong Eui Song

  DOI：10.1002/adsc.201000289

  日期：2010.9.10

  The bifunctional Cinchona‐based sulfonamide catalysts showed the highest levels of enantioselectivity reported to date in the alcoholytic desymmetrization of meso‐glutaric anhydrides. Density functional theory (DFT) computational studies provide detailed insight into the observed sense of enantioselectivity. Moreover, detailed experimental studies and single crystal X‐ray analysis confirmed that these

  双功能金鸡纳为基础的磺胺催化剂表现出的对映选择性的最高水平的alcoholytic desymmetrization报告的日期观戊二酸酐。密度泛函理论（DFT）计算研究为观察到的对映选择性提供了详细的见识。此外，详细的实验研究和单晶X射线分析证实，这些双功能有机催化剂3在溶液和固态均不会形成H键结合的自聚集体。这种方法的合成效用还在合成重要的γ-氨基酸（例如（S）-普瑞巴林）中得到了证明。对映体纯（S的许多不对称合成）-迄今为止报道的普瑞巴林，我们的合成需要最少的步骤和最简单的步骤。
• Development of Bifunctional Thiourea Organocatalysts Derived from a Chloramphenicol Base Scaffold and their Use in the Enantioselective Alcoholysis of<i>meso</i>Cyclic Anhydrides
  作者：Lin-Jie Yan、Hai-Feng Wang、Wen-Xue Chen、Yuan Tao、Kai-Jun Jin、Fen-Er Chen

  DOI：10.1002/cctc.201600228

  日期：2016.7.6

  chloramphenicol‐base‐derived thiourea organocatalysts, (1S,2R)‐12 a–f and (1R,2R)‐15 a–c, and their use in the enantioselective alcoholysis of meso‐anhydrides are described. In particular, hemiesters afforded excellent enantioselectivities if low loadings of (1S,2R)‐12 a–f were used. Almost no enantioselectivities were achieved with the use of (1R,2R)‐15 a–c. This technique was used to synthesize (R)‐(−)‐baclofen

  新的氯霉素基硫脲有机催化剂（1 S，2 R）-12 a - f和（1 R，2 R）15 a - c的合成及其在介孔酸酐的对映选择性醇解中的应用描述。特别是，如果使用低负荷的（1 S，2 R）-12 a – f负载，半酯具有出色的对映选择性。使用（1 R，2 R）‐ 15 a – c几乎没有达到对映选择性。该技术用于合成（R）-（-）-baclofen。
• A family of novel bifunctional organocatalysts: Highly enantioselective alcoholysis of meso cyclic anhydrides and its application for synthesis of the key intermediate of P2X7 receptor antagonists
  作者：Hong-Jun Yang、Fang-Jun Xiong、Jie Li、Fen-Er Chen

  DOI：10.1016/j.cclet.2013.04.009

  日期：2013.7

  Abstract A family of novel squaramides/sulfamides based on 1,2-alkamine was developed as chiral bifunctional catalysts to promote the asymmetric alcoholysis of meso cyclic anhydrides. The hemiesters were obtained in high yield with up to 93% ee. The usefulness of this methodology was demonstrated in the asymmetric synthesis of the key intermediate of P2X7 receptor antagonists.

  摘要研制了一系列以1,2-链胺为基础的新型方酸/亚磺酰胺作为手性双官能催化剂，以促进内消旋环酸酐的不对称醇解。半酯以高达93％ee的高收率获得。P2X7受体拮抗剂关键中间体的不对称合成证明了该方法的有效性。
• Novel process
  申请人：SmithKline Beecham plc

  公开号：US20020133011A1

  公开（公告）日：2002-09-19

  1 Compounds of structure ( 1 ) are obtained by reduction of compounds of the structures 2 Compounds of structure ( 1 ), especially where Z is a hydrogen atom or a 3,4-methylenedioxyphenyl group, are important intermediates for inter alia paroxetine.

  1. 结构（1）的化合物通过还原结构2的化合物得到。 2. 结构（1）的化合物，特别是当Z为氢原子或3,4-亚甲二氧基苯基基团时，是制备帕罗西汀等重要中间体。