(R)-2-bromopropionic acid benzyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-2-bromopropionic acid benzyl ester
• 英文别名: (R)-benzyl 2-bromopropanoate；benzyl (R)-2-bromopropanoate；benzyl (R)-2-bromopropionate；benzyl-(R)-2-bromo-propionate；benzyl (2R)-2-bromopropanoate
• 化学式: C₁₀H₁₁BrO₂
• 分子量: 243.1
• InChiKey: IZZIPPQWYVRGRS-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氨基-L-丁酸乙酯 、 (R)-2-bromopropionic acid benzyl ester 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 8.0h， 生成 N-[1(S)-(乙氧基羰基)丁基]-L-丙氨酸苄酯
  参考文献：
  名称：

  [EN] NOVEL METHOD FOR PREPARATION OF CRYSTALLINE PERINDOPRIL ERBUMINE
  [FR] NOUVELLE METHODE DE PREPARATION DE PERINDOPRIL ERBUMINE CRISTALLINE

  摘要：

  一种制备结晶盐酸培哌普利的方法，其化学式为(II)，表现出X射线（粉末）衍射图谱，类似于所示图中的图谱。该方法包括将化学式(I)的培哌普利溶液在从N,N-二甲基甲酰胺或低碳链脂肪醛和酮的二甲基缩醛中选择的溶剂中与叔丁胺反应，并通过加热反应混合物至沸腾，热过滤，逐渐冷却至20°C至30°C，进一步冷却至0°C至15°C 30分钟至1小时，最后过滤和干燥晶体来结晶盐酸培哌普利。

  公开号：

  WO2005037788A1
• 作为产物：
  描述：

  (R)-(+)-2-溴丙酸 、 苯甲醇 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以82%的产率得到(R)-2-bromopropionic acid benzyl ester
  参考文献：
  名称：

  Synthesis and Evaluation of Noncovalent Naphthalene-Based KEAP1-NRF2 Inhibitors

  摘要：

  The oxidative stress response, gated by the protein-protein interaction of KEAP1 and NRF2, has garnered significant interest in the past decade. Misregulation in this pathway has been implicated in disease states such as multiple sclerosis, rheumatoid arthritis, and diabetic chronic wounds. Many of the known activators of NRF2 are electrophilic in nature and may operate through several biological pathways rather than solely through the activation of the oxidative stress response. Recently, our lab has reported a nonelectrophilic, monoacidic, naphthalene-based NRF2 activator which exhibited good potency in vitro. Herein, we report a detailed structure-activity relationship of naphthalene-based NRF2 activators, an X-ray crystal structure of our monoacidic KEAP1 inhibitor, and identification of an underexplored area of the NRF2 binding pocket of KEAP1.

  DOI：

  10.1021/acsmedchemlett.9b00631

文献信息

• [EN] PROCESS FOR PREPARATION OF PERINDOPRIL AND SALTS THEREOF<br/>[FR] PROCEDE DE PREPARATION DE PERINDOPRIL ET DE SELS DE CELUI-CI
  申请人：LUPIN LTD

  公开号：WO2004075889A1

  公开（公告）日：2004-09-10

  A process for preparation of perindopril of formula (II) and salts thereof which is simple, safe, convenient and cost-effective. The process involves reaction of compound of formula (I), wherein X is chlorine or bromine with compound of formula (VII) wherein A signifies that the six-membered ring of the bicyclic system is either saturated or unsaturated, followed by catalytic hydrogenation to give the perindopril of formula (II).

  一种制备分子式为（II）的贝那普利及其盐的方法，该方法简单、安全、方便且具有成本效益。该过程涉及将具有分子式（I）的化合物（其中X为氯或溴）与具有分子式（VII）的化合物（其中A表示双环系统的六元环是饱和的或不饱和的）发生反应，然后进行催化氢化以得到分子式为（II）的贝那普利。
• Novel Applications of the Schöllkopf Chiral Auxiliary: A New and Efficient Enantioselective Synthesis of β-Lactams Possessing a C-4 Quaternary Stereocenter
  作者：Plato A. Magriotis、Stamatia Vassiliou、Constantinos Dimitropoulos

  DOI：10.1055/s-2003-42103

  日期：——

  A new method for the enantioselective synthesis of substituted β-lactams is described based upon an improved alkylation of substituted Schollkopf chiral auxiliaries by α-haloacetate esters, employing tert-butyllithium as the deprotonating base, and the efficient conversion of the resulting quaternary 2,5-diketopiperazines to the targeted β-lactams.

  描述了一种用于对映选择性合成取代 β-内酰胺的新方法，该方法基于取代 Schollkopf 手性助剂通过 α-卤代乙酸酯的改进烷基化，使用叔丁基锂作为去质子化碱，以及所得季铵 2,5 的有效转化-二酮哌嗪到目标 β-内酰胺。
• Process for preparation of perindopril and salts thereof
  申请人：Datta Debashish

  公开号：US20060276659A1

  公开（公告）日：2006-12-07

  A process for preparation of perindopril of formula (II) and salts thereof which is simple, safe convenient and cost-effective. The process involves reaction of compound of formula (I), wherein X is chlorine or bromine with compound of formula (VII) wherein A signifies that the six-membered ring of the bicyclic system is either saturated or unsaturated to give compound of formula (VIII), wherein A is as defined above, followed by catalytic hydrogenation of the compound of formula (VIII) thus obtained to give the perindopril of formula (II). The above process for the manufacture of perindopril would specifically avoid the use of harmful chemicals like phosgene or costly coupling agents like dicyclohexylcarbodiimide and 1-hydroxybenxotriazole usually used for such manufacture. The process would also not require any intervention of a catalyst and does not require any alkaline or acidic reaction conditions. Importantly, the process provides for manufacture of perindopril with high stereoselectively giving perindopril (II) having (S)-configuration in all the five chiral centres of the molecule, conforming to pharmacoepeial specifications. The invention also relates to a method for preparation of the compound of formula (I) and also to a method for preparation of N-[(S)- 1 -carbethoxybutyl]-(S)-alanine of formula (III) used in the process.

  一种制备公式（II）的普利度洛及其盐的方法，该方法简单、安全、方便、经济。该方法涉及公式（I）化合物（其中X为氯或溴）与公式（VII）化合物反应（其中A表示双环系统的六元环饱和或不饱和），以得到公式（VIII）化合物（其中A如上所定义），随后对所得的公式（VIII）化合物进行催化氢化，以得到公式（II）的普利度洛。上述制备普利度洛的方法将特别避免使用有害化学品如光气或昂贵的偶联剂如二环己基碳二亚胺和1-羟基苯并三唑通常用于此类制造。该方法也不需要催化剂的干预，也不需要碱性或酸性反应条件。重要的是，该方法提供了高立体选择性的普利度洛制造，使得分子的所有五个手性中心都具有（S）-构型，符合药典规格。本发明还涉及公式（I）化合物的制备方法，以及在该过程中使用的公式（III）N-[(S)-1-羧乙氧基丁基] -（S）-丙氨酸的制备方法。
• Novel method for preparation of crystalline perindopril erbumine
  申请人：Singh Pal Girij

  公开号：US20070149604A1

  公开（公告）日：2007-06-28

  A process for preparation of crystalline perindopril erbumine of formula (II) which exhibits the X-ray (powder) diffraction pattern like that shown in FIG. 2 The process comprises reacting a solution of perindopril of formula (I), in a solvent selected from N,N-dimethylformamide, dimethyl acetals of lower aliphatic aldehydes, dimethyl ketals of lower aliphatic ketones and 1,2-dialkoxyethane with tertiary butylamine and crystallization of the erbumine salt thus obtained by heating the reaction mixture to reflux, filtering hot, cooling gradually to 20° C. to 30° C., and further cooling to 0° C. to 15° C. for 30 minutes to 1 hour and finally filtering off and drying the crystals.

  一种制备式（II）晶体型的依普利酸厄贝林的方法，其展现出类似于图2所示的X射线（粉末）衍射图谱。该方法包括在从N,N-二甲基甲酰胺、低级脂肪醛的二甲基缩醛、低级脂肪酮的二甲基缩酮和1,2-二烷氧基乙烷中选择的溶剂中反应式（I）的依普利酸溶液，与叔丁胺反应，并通过将反应混合物加热至回流，过滤热，逐渐冷却至20°C至30°C，然后进一步冷却至0°C至15°C，保持30分钟至1小时，最后过滤并干燥晶体来结晶得到厄贝林盐。
• Method for preparation of crystalline perindopril erbumine
  申请人：Lupin Ltd

  公开号：US07456296B2

  公开（公告）日：2008-11-25

  A process for preparation of crystalline perindopril erbumine of formula (II) which exhibits the X-ray (powder) diffraction pattern like that shown in FIG. 2 The process comprises reacting a solution of perindopril of formula (I), in a solvent selected from N,N-dimethylformamide, dimethyl acetals of lower aliphatic aldehydes, dimethyl ketals of lower aliphatic ketones and 1,2-dialkoxyethane with tertiary butylamine and crystallization of the erbumine salt thus obtained by heating the reaction mixture to reflux, filtering hot, cooling gradually to 20° C. to 30° C., and further cooling to 0° C. to 15° C. for 30 minutes to 1 hour and finally filtering off and drying the crystals.

  一种制备式（II）晶体型的便利普利酯的方法，该方法展现了如图2所示的X射线（粉末）衍射图案。该方法包括在N，N-二甲基甲酰胺，低级脂肪醛的二甲基缩醛，低级脂肪酮的二甲基缩酮和1,2-二烷氧乙烷中选择性溶剂中反应式（I）的便利普利酯溶液与叔丁胺，然后通过将反应混合物加热至回流，过滤热，逐渐冷却至20℃至30℃，进一步冷却至0℃至15℃，静置30分钟至1小时，最后过滤并干燥晶体来结晶得到便利普利酯盐。