ethyl (2S,4S)-4-methyl-2-piperidinecarboxylate L-(+)-tartarate | 1401618-23-2

• 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: ethyl (2S,4S)-4-methyl-2-piperidinecarboxylate L-(+)-tartarate
• 英文别名: ethyl (2S,4S)-4-methyl-2-piperidinecarboxylate L-tartrate；Ethyl (2S,4S)-4-methylpiperidine-2-carboxylate (2R,3R)-2,3-dihydroxysuccinate；(2R,3R)-2,3-dihydroxybutanedioic acid;ethyl (2S,4S)-4-methylpiperidine-2-carboxylate
• CAS: 1401618-23-2
• 化学式: C₄H₆O₆*C₉H₁₇NO₂
• 分子量: 321.328
• InChiKey: LKQJOTYRDSQDNJ-QRJBQDOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.18
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  153.39
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  阿加曲班杂质E(盐酸盐) 在 氯化亚砜 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 0.5h， 生成 (2R,4R)-4-甲基-2-哌啶甲酸乙酯L-酒石酸盐 、 ethyl (2S,4S)-4-methyl-2-piperidinecarboxylate L-(+)-tartarate
  参考文献：
  名称：

  PROCESS INTERMEDIATES AND METHODS FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE

  摘要：

  提供了一种合成Argatroban monohydrate的关键中间体的方法，该中间体是乙酸(2R,4R)-1-[(2S)-2-氨基-5-[[亚硝基氨基)甲基]氨基]-1-氧代戊基]-4-甲基哌啶-2-羧酸乙酯，与HCl混合。同时也提供了这些中间体。

  公开号：

  US20140088310A1

文献信息

• [EN] METHOD FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE<br/>[FR] PROCÉDÉ DE PRÉPARATION D'INTERMÉDIAIRES DE PROCÉDÉ POUR LA SYNTHÈSE DE L'ARGATROBAN MONOHYDRATE
  申请人：LUNDBECK PHARMACEUTICALS ITALY S P A

  公开号：WO2012136504A1

  公开（公告）日：2012-10-11

  Object of the present invention is a method for the synthesis of a key intermediate for the synthesis of Argatroban monohydrate, ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4- methylpiperidine-2-carboxylate compounded with HCl.

  本发明的对象是一种用于合成Argatroban monohydrate的关键中间体的方法，该中间体为乙酸(2R,4R)-1-[(2S)-2-氨基-5-[[亚硝胺基]亚氨基]-1-氧代戊基]-4-甲基哌啶-2-羧酸乙酯，并与HCl复合。
• The Role of Diastereomer Impurity in Oiling-Out during the Resolution of <i>trans</i>-4-Methyl-2-piperidine Carboxylic Ethyl Ester Enantiomers by Crystallization
  作者：Riju Ren、Dengqiong Sun、Tingting Wei、Shixin Zhang、Junbo Gong

  DOI：10.1021/op500026z

  日期：2014.6.20

  Isolating enantiomers by crystallization via diastereomer salt formation is widely used in the pharmaceutical industry. Unfortunately, we found that, when some diastereomer impurity exists, oiling-out will take place and significantly decrease the resolution efficiency. To identify the role of impurities in oiling-out, three series of chiral resolution of trans-4-methyl-2-piperidine carboxylic ethyl ester (trans-4MPE) with different levels of diastereomer impurity were performed. Using process analytical technologies (PAT) technologies, the demixing region was identified by measuring TL-L curves and supersolubility curves for different series. It was found that a series with a higher level of impurity has a higher TL-L point and a wider demixing region. Besides, it seems that the resolution efficiency through oiling-out, as well as the crystallization kinetics, was significantly decreased. Here we initially put forward this particular diastereomer purification problem, where the impurity has a positive effect on oiling-out. To reduce or eliminate oiling-out, an efficient prepurification strategy must be ensured.