(S)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester | 114315-60-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester
• 英文别名: butyl (S)-2-(6-methoxy-2-naphthyl)propanoate；Butyl 2-(6-methoxy-2-naphthyl)propionat；(S)-naproxen n-butyl ester；Naproxen butyl ester；butyl (2S)-2-(6-methoxynaphthalen-2-yl)propanoate
• CAS: 114315-60-5
• 化学式: C₁₈H₂₂O₃
• 分子量: 286.371
• InChiKey: VIKFUEUFSFCFQU-ZDUSSCGKSA-N

物化性质

• 熔点：
  66-67 °C
• 沸点：
  400.4±20.0 °C(Predicted)
• 密度：
  1.072±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester 在 4-二甲氨基吡啶 、 三溴化硼 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.92h， 生成
  参考文献：
  名称：

  Wu, S.-L.; Chen, D.-G.; Hsieh, W.-J., Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 1994, vol. 250, p. 153 - 160

  摘要：

  DOI：
• 作为产物：
  描述：

  naproxen chloride 在 whole cells of Trichosporon sp 作用下， 以 phosphate buffer 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid butyl ester
  参考文献：
  名称：

  Enzymatic resolution of naproxen

  摘要：

  Trichosporon sp. (TSL), a newly found strain isolated from a locally fermented cottage cheese has been found to be highly stereoselective in the resolution of (S)-(+)-naproxen (ee >99%, Esimilar to500) from the corresponding racemic methyl ester. The process of resolution using whole cells has been scaled up to multi-kg level. Optimization of experimental conditions including downstream processing at 80-100 g/L substrate concentration with >90% recovery has been achieved. Changes in the physical parameters such as the particle size of the substrate play an important role in the resolution kinetics. A new strain of Trichosporon sp. having high cell density in cultivation (>60 g dry cell mass L-1 in 14-16 h) is found to be sufficiently stable for two years in dry powder form at 5-8degreesC. The viability of the resolution process has been further improved by the development of a simple racemization process for the enriched (R)-(-)-ester. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(03)00492-0

文献信息

• A Great Improvement of the Enantioselectivity of Lipase-Catalyzed Hydrolysis and Esterification Using Co-Solvents as an Additive
  作者：Tomohiro Nishigaki、Yoshitaka Yasufuku、Sayuri Murakami、Yasuhito Ebara、Shin-ichi Ueji

  DOI：10.1246/bcsj.81.617

  日期：2008.5.15

  improvement of the enantioselectivity of lipase-catalyzed hydrolysis of butyl 2-(4-substituted phenoxy)propanoates in an aqueous buffer solution. On the other hand, lipase lyophilized from an aqueous solution containing the co-solvents catalyzed highly enantioselective esterification of 2-(4-substituted phenoxy)propionic acids, 2-(4-isobutylphenyl)propionic acid (ibuprofen), and 2-(6-methoxy-2-naphthyl)propionic

  添加共溶剂如四氢呋喃导致脂肪酶催化的 2-(4-取代苯氧基)丙酸丁酯在缓冲水溶液中水解的对映选择性大大提高。另一方面，从含有共溶剂的水溶液中冻干的脂肪酶催化 2-（4-取代苯氧基）丙酸、2-（4-异丁基苯基）丙酸（布洛芬）和 2-（6 -甲氧基-2-萘基）丙酸（萘普生）在有机溶剂中。对于某些底物，观察到 E 值增加了两个数量级。由共溶剂添加引起的对映选择性增强的起源主要归因于错误结合的对映异构体的初始反应速率显着减慢，与正确结合的对映体相比。从FT-IR、CD和ESR光谱的结果来看，还发现共溶剂的加入导致脂肪酶三级结构的部分破坏。
• Ester des Naproxens als potentielle Prodrugs zur Hautpenetration, 1. Mitt.: Synthese und physikochemische Eigenschaften
  作者：Horst Weber、Klaudia Meyer-Trümpener

  DOI：10.1002/ardp.19943270511

  日期：——

  Standardmethoden synthetisiert. Durch dynamische Differenzkalorimetrie DSC wurden der Schmelzpunkt und die Schmelzenthalpie der einzelnen Verbindungen erhalten. Mittels HPLC wurde die Sättigungskonzentration in Wasser bestimmt. Der Verteilungskoeffizient Octanol/Wasser wurde nach Rekker und Mannhold berechnet und der Rm‐Wert durch RP‐DC bestimmt. Die beiden letzten Parameter lassen sich mit hoher Signifikanz

  使用标准方法合成了非甾体抗炎药萘普生 [2-(6-甲氧基-2-萘基) 丙酸] 的各种酯。各个化合物的熔点和熔融焓通过动态差示量热法 DSC 获得。水中的饱和浓度通过HPLC测定。辛醇/水分配系数根据 Rekker 和 Mannhold 计算，Rm 值通过 RP-DC 确定。最后两个参数可以与高显着性相关。
• [EN] METHOD FOR THE PREPARATION OF NAPROXEN CHLORIDE<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE CHLORURE DE NAPROXÈNE
  申请人：LONZA AG

  公开号：WO2012069423A1

  公开（公告）日：2012-05-31

  The invention relates to a method for the preparation of 2-(6'-methoxy-2'-naphthyl)propionic acid chloride(naproxen chloride) using phosgene, and a method for the preparation of esters and amides derived from the thus prepared naproxen chloride.

  本发明涉及使用光气的制备2-(6'-甲氧基-2'-萘基)丙酸氯化物（萘普生氯化物）的方法，以及基于所制备的萘普生氯化物制备酯和酰胺的方法。
• Multi odd–even effects on cell parameters, melting points, and optical properties of chiral crystal solids based on S-naproxen
  作者：Gui-Mei Tang、Jin-Hua Wang、Chao Zhao、Yong-Tao Wang、Yue-Zhi Cui、Fei-Yue Cheng、Seik Weng Ng

  DOI：10.1039/c5ce01345c

  日期：——

  A set of chiral crystal solids with odd and even numbers of carbon atoms based on S-naproxen, ester S-naproxen-R1 (R1 = H, methyl, ethyl, n-propyl, n-butyl, and n-amyl), has been prepared, alternatively crystallizing in the space groups P21 and P212121, respectively, which shows the multi odd–even effects on cell parameters, melting points, and optical properties.

  一组基于S-萘普生，酯S-萘普生-R 1（R 1 = H，甲基，乙基，正丙基，正丁基和正戊基）的具有奇数和偶数碳原子的手性晶体固体制备了，分别在空间群P 2 1和P 2 1 2 1 2 1 1中结晶，这显示了对电池参数，熔点和光学性质的多重奇偶影响。
• Influence of OR ester group length on the catalytic activity and enantioselectivity of free lipase and immobilized in membrane used for the kinetic resolution of naproxen esters
  作者：L GIORNO、E DAMORE、E DRIOLI、R CASSANO、N PICCI

  DOI：10.1016/j.jcat.2007.01.021

  日期：2007.4.25

  Lipases are suitable catalysts for the kinetic resolution of racemic mixtures due to their ability to discriminate between enantiomers. For this reason, they have been studied largely to develop reactors for the production of optically pure enantiomers. The main problem in these productive systems is enzyme stability and enantiocatalytic selectivity as a function of time. In this work, the enantiocatalytic properties of lipase as a function of the -OR group length were studied. The methyl, butyl, and octyl esters of naproxen were synthesized and used as reagents. The lipase was used as a free agent and immobilized in a polymeric membrane reactor. The results show that selectivity and stability of the enzyme improved while catalytic activity decreased with the -OR length group. The immobilized enzyme had higher activity compared with the free enzyme. (C) 2007 Elsevier Inc. All rights reserved.