(S)-3-(4-fluorophenyl)-glutaric acid monomethyl ester | 216690-16-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (S)-3-(4-fluorophenyl)-glutaric acid monomethyl ester
• 英文别名: methyl (S)-3-(4-fluorophenyl)glutarate；(3R)-methyl hydrogen 3-(4-fluorophenyl)pentane-1,5-dioate；(S)-3-(4-fluorophenyl)pentanedioic acid monomethyl ester；(3S)-3-(4-fluorophenyl)-5-methoxy-5-oxopentanoic acid
• CAS: 216690-16-3
• 化学式: C₁₂H₁₃FO₄
• 分子量: 240.231
• InChiKey: YCDQTTZPMJRWCQ-VIFPVBQESA-N

物化性质

• 熔点：
  90-91 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  363.3±32.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

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：

  (S)-3-(4-fluorophenyl)-glutaric acid monomethyl ester 以 硼烷 为溶剂， 生成 R-1-benzyl-3-(4'-fluorophenyl)-piperidine-2-one
  参考文献：
  名称：

  Novel process

  摘要：

  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。

  公开号：

  US20020133011A1
• 作为产物：
  描述：

  3-(4-氟苯基)戊二酸 在 Novozym 435 、 乙酰氯 作用下， 以 异丙醚 为溶剂， 反应 27.0h， 生成 (S)-3-(4-fluorophenyl)-glutaric acid monomethyl ester
  参考文献：
  名称：

  Enzymatic desymmetrization of 3-arylglutaric acid anhydrides

  摘要：

  Optically active (R)- and (S)-3-arylglutaric acid monoesters 3 were synthesized in quantitative yields and good stereoselectivities by lipase-catalyzed desymmetrization of the corresponding 3-arylglutaric anhydrides 2 with alcohols. It was observed that the stereochemical outcome of the reaction was influenced by the substituents present on the aromatic ring. The influence of the enzyme, alcohol, and solvent was systematically examined. Absolute configurations of the monoesters 3 were assigned by chemical correlation to corresponding lactones 4. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.06.025

文献信息

• 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。
• Pilot-Plant Preparation of 3,4-Dihydropyridin-2-one Derivatives, the Core Structures of P2X₇Receptor Antagonists
  作者：Xiaojun Huang、Scott Broadbent、Charles Dvorak、Shu-Hai Zhao

  DOI：10.1021/op1000447

  日期：2010.5.21

  The pilot-plant syntheses of 3 and 4, the core structures of a series of P2X7 antagonists are described. The sole stereogenic center in the dihydropyridinone ring was generated by catalytic desymmetrization. Selective formylation, followed by a tandem imination/lactamization sequence, produced the 3,4-dihydropyridin-2-one ring. The compounds 3 and 4 were produced at multikilogram scale in good overall

  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 ）。
• Asymmetric synthesis of (−)-paroxetine using PLE hydrolysis
  作者：Marvin S Yu、Ivan Lantos、Zhi-Qiang Peng、J Yu、Thomas Cacchio

  DOI：10.1016/s0040-4039(00)00942-4

  日期：2000.7

  (-)-Paroxetine hydrochloride was produced asymmetrically in seven steps starting from 4-fluoro benzaldehyde. The stereocenter at C-4 was initially set through desymmetrization of glutaric acid bis methyl ester 4 by PLE hydrolysis. A unique one-pot reduction-alkylation procedure was then developed to provide entry to lactam 2 with the appropriate absolute stereochemistry. (C) 2000 Elsevier Science Ltd. All rights reserved.

  (-)-Paroxetine盐酸盐是通过七步反应以4-氟苯甲醛为起始原料不对称合成的。C-4位的手性中心最初是通过5-羟基脯氨酸酯(glutaric acid bis methyl ester)的PLE水解消除对称性而设置的。随后，开发了一种独特的单锅还原-烷基化步骤，以获得具有适当绝对构型的内酰胺2。©2000 Elsevier Science Ltd. 保留所有权利。
• [EN] NOVEL PROCESS<br/>[FR] NOUVEAU PROCEDE
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1998053824A1

  公开（公告）日：1998-12-03

  (EN) Compounds of structure (1) are obtained by reduction of compounds of the structures (2a), (2b), (4a), (4b). Compounds of structure (1), especially where Z is a hydrogen atom or a 3,4-methylenedioxyphenyl group, are important intermediates for $i(inter alia) paroxetine.(FR) La présente invention concerne des composés représentés par la structure (1) obtenus par réduction des composés des structures (2a), (2b), (4a) et (4b). Les composés de la structure (1) sont d'importants intermédiaires entre autres pour la paroxétine, notamment si Z représente un atome d'hydrogène ou un groupe 3,4-méthylènedioxyphényle.

  (EN) 通过还原结构为(2a)，(2b)，(4a)，(4b)的化合物，可以获得结构为(1)的化合物。结构为(1)的化合物，特别是当Z是氢原子或3,4-亚甲二氧基苯基时，是重要的中间体，用于生产帕罗西汀等药物。 (FR) 由结构为(2a)，(2b)，(4a)，(4b)的化合物还原而得到结构为(1)的化合物。结构为(1)的化合物是重要的中间体，用于生产帕罗西汀等药物，特别是当Z表示氢原子或3,4-亚甲二氧基苯基时。