(2S,3R)-1-(二甲基氨基)-3-(3-甲氧基苯基)-2-甲基戊-3-醇盐酸盐 | 809282-45-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2S,3R)-1-(二甲基氨基)-3-(3-甲氧基苯基)-2-甲基戊-3-醇盐酸盐
• 英文名称: (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride
• 英文别名: (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methylpentan-3-ol;hydrochloride
• CAS: 809282-45-9
• 化学式: C₁₅H₂₅NO₂*ClH
• 分子量: 287.83
• InChiKey: JWPQTVRDQHIIHD-SBKWZQTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.91
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  32.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3R)-1-(二甲基氨基)-3-(3-甲氧基苯基)-2-甲基戊-3-醇盐酸盐 以90的产率得到(R)-3-(3-methoxyphenyl)-N,N,2-trimethylpent-3-en-1-amine
  参考文献：
  名称：

  Process for the Preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol

  摘要：

  本发明涉及一种制备（1R，2R）-3-二甲氨基-1-乙基-2-甲基丙基苯酚的方法。

  公开号：

  US20100099916A1
• 作为产物：
  描述：

  (S)-3-(二甲基氨基)-1-(3-甲氧基苯基)-2-甲基-1-丙酮 以100% ee; 82的产率得到(2S,3R)-1-(二甲基氨基)-3-(3-甲氧基苯基)-2-甲基戊-3-醇盐酸盐
  参考文献：
  名称：

  Process for the Preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol

  摘要：

  本发明涉及一种制备（1R，2R）-3-二甲氨基-1-乙基-2-甲基丙基苯酚的方法。

  公开号：

  US20100099916A1

文献信息

• [DE] VERFAHREN ZUR HERSTELLUNG SUBSTITUIERTER 3-ARYL-BUTYL-AMINVERBINDUNGEN<br/>[EN] METHOD FOR THE PRODUCTION OF SUBSTITUTED 3-ARYL-BUTYL AMINE COMPOUNDS<br/>[FR] PROCEDE DE PRODUCTION DES COMPOSES D'AMINE 3-ARYLE-BUTYLE SUBSTITUE
  申请人：GRUENENTHAL GMBH

  公开号：WO2004108658A1

  公开（公告）日：2004-12-16

  Die vorliegende Erfindung betrifft ein Verfahren zur Dehydratisierung substituierter 1-Amino-3-aryl-butan-3-ol­Verbindungen zur Herstellung substituierter 3-Aryl-butylamin-Verbindungen.

  这项发明涉及一种去水代替的1-氨基-3-芳基丁-3-醇化合物制备代替的3-芳基丁胺化合物的方法。
• [EN] NEW PROCESS FOR THE SYNTHESIS OF TAPENTADOL AND INTERMEDIATES THEREOF<br/>[FR] NOUVEAU PROCÉDÉ POUR LA SYNTHÈSE DE TAPENTADOL ET SES INTERMÉDIAIRES
  申请人：ARCHIMICA SRL

  公开号：WO2012001571A1

  公开（公告）日：2012-01-05

  The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high stereoselectivity due to the presence of the benzyl group as substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol equilibrium towards the desired enantiomer and amplifies the capacity of the stereocenter present in the compound (VII) to orient the nucleophilic addition of the organometallic compound at the carbonyl towards the desired stereoisomer. This substitution thus allows obtaining a considerable increase of the yields in this step, and consequently allows significantly increasing the overall yield of the entire tapentadol synthesis process. A further object of the present invention is constituted by the tapentadol free base in solid form, obtainable by means of the process of the invention. Still another object of the invention is represented by the crystalline forms I and II of the tapentadol free base. A further object of the present invention is the mixture of the crystalline forms I and II of the tapentadol free base.

  本发明的目的是提供一种新的合成托瑞哌酯的方法，包括自由基和盐酸盐形式。该方法包括烷基化酮（VII）的步骤，生成化合物（VIII），如图1所示，由于苄基作为氨基取代基的存在而具有高立体选择性。令人惊讶的是，这种取代使得酮-烯醇平衡向所需的对映体转移，并放大了化合物（VII）中存在的立体中心定向有机金属化合物对羰基的亲核加成朝向所需的立体异构体的能力。这种取代因此允许在此步骤中获得相当大的产量增加，并因此显著提高整个托瑞哌酯合成过程的总产量。本发明的另一个目的是通过本发明的方法获得固态的托瑞哌酯自由基。本发明的另一个目的是托瑞哌酯自由基的晶体形式I和II。本发明的另一个目的是托瑞哌酯自由基的晶体形式I和II的混合物。
• PROCESS FOR THE SYNTHESIS OF TAPENTADOL AND INTERMEDIATES THEREOF
  申请人：Motta Giuseppe

  公开号：US20130178644A1

  公开（公告）日：2013-07-11

  The object of the present invention is a new process for the synthesis of tapentadol, both as free base and in hydrochloride form, which comprises the step of alkylation of the ketone (VII) to yield the compound (VIII), as reported in Diagram 1, with high stereoselectivity due to the presence of the benzyl group as substituent of the amino group. It was surprisingly found that this substitution shifts the keto-enol equilibrium towards the desired enantiomer and amplifies the capacity of the stereocenter present in the compound (VII) to orient the nucleophilic addition of the organometallic compound at the carbonyl towards the desired stereoisomer. This substitution thus allows obtaining a considerable increase of the yields in this step, and consequently allows significantly increasing the overall yield of the entire tapentadol synthesis process. A further object of the present invention is constituted by the tapentadol free base in solid form, obtainable by means of the process of the invention. Still another object of the invention is represented by the crystalline forms I and II of the tapentadol free base. A further object of the present invention is the mixture of the crystalline forms I and II of the tapentadol free base.

  本发明的目标是一种新的合成替帕酮的过程，包括自由基和盐酸盐形式，其中包括烷基化酮（VII）的步骤，得到化合物（VIII），如图1所示，由于苄基作为氨基的取代基存在，具有高度的立体选择性。惊奇地发现，这种取代使得酮-烯醇平衡向所需的对映体转移，并放大了化合物（VII）中的立体中心的能力，以定向有机金属化合物在羰基上的亲核加成，朝向所需的立体异构体。这种取代因此允许在这一步骤中获得相当大的产量增加，从而显着提高整个替帕酮合成过程的总产量。本发明的另一个目标是通过本发明的过程获得固态的替帕酮自由基。本发明的另一个目标是替帕酮自由基的结晶形式I和II。本发明的另一个目标是替帕酮自由基结晶形式I和II的混合物。
• NOVEL PROCESS FOR PREPARING HIGHLY PURE TAPENTADOL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
  申请人：Khunt Mayur Devjibhai

  公开号：US20130096347A1

  公开（公告）日：2013-04-18

  Provided herein is a novel, commercially viable and industrially advantageous process for the preparation of 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol (Tapentadol), or a pharmaceutically acceptable salt thereof, and its intermediates, in high yield and purity. Provided also herein are novel solid state forms of tapentadol intermediates and processes for their preparation thereof. Provided further herein is a purification process for preparing highly pure tapentadol hydrochloride.

  本文提供了一种新颖的、商业上可行的和工业上有利的制备3-[(1R,2R)-3-(二甲氨基)-1-乙基-2-甲基丙基]苯酚（Tapentadol）或其药学上可接受的盐及其中间体的高产率和高纯度的过程。本文还提供了Tapentadol中间体的新固态形式及其制备方法。本文还提供了一种纯化过程，用于制备高纯度的Tapentadol盐酸盐。
• [EN] PROCESS FOR PREPARING L-PHENYL-3-DIMETHYLAMINOPROPANE DERIVATIVE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE L-PHÉNYL-3-DIMÉTHYLAMINOPROPANE
  申请人：IND SWIFT LAB LTD

  公开号：WO2012038974A1

  公开（公告）日：2012-03-29

  Provided is a process for the preparing l-phenyl-3-dimethylaminopropane derivatives of formula I, (The formula should be inserted here) and its pharmaceutically acceptable salts thereof via novel intermediates.

  提供一种制备I式（此处应插入公式）的L-苯基-3-二甲氨基丙烷衍生物及其药物可接受的盐的过程，通过新型中间体实现。