1-Amino-3-methyl-octan-3-ol | 60939-26-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-Amino-3-methyl-octan-3-ol
• 英文别名: 1-Amino-3-methyloctan-3-ol
• CAS: 60939-26-6
• 化学式: C₉H₂₁NO
• 分子量: 159.272
• InChiKey: ISFWBTDZQQOTMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-Amino-3-methyl-octan-3-ol 在 盐酸 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 生成 2-[1-(3-Hydroxy-3-methyl-octyl)-ureido]-nonanedioic acid dimethyl ester
  参考文献：
  名称：

  10,12-Diazaprostaglandin analogues

  摘要：

  DOI：

  10.1016/s0040-4039(01)86197-9

文献信息

• [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.

  本发明的对象是一种用于合成替本多尔（tapentadol）的新工艺，包括将酮（VII）烷基化以得到化合物（VIII），如图1所示，其具有高立体选择性，这是由于苄基作为氨基的取代基存在。令人惊讶地发现，这种取代将酮-烯醇平衡转向所需的对映体，并增强了化合物（VII）中存在的立体中心引导有机金属化合物在羰基上的亲核加成朝向所需立体异构体的能力。这种取代因此允许在这一步骤中获得产量的显着增加，从而显著提高整个替本多尔合成过程的总产量。本发明的另一个对象是通过本发明的方法获得的固态替本多尔游离碱。本发明的另一个对象是替本多尔游离碱的结晶形式I和II。本发明的另一个对象是替本多尔游离碱的结晶形式I和II的混合物。
• [EN] NEW PROCESS FOR THE PREPARATION OF TAPENTADOL AND INTERMEDIATES THEREOF<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE TAPENTADOL ET DE SES INTERMÉDIAIRES
  申请人：ARCHIMICA SRL

  公开号：WO2011067714A1

  公开（公告）日：2011-06-09

  The present invention refers to a new process for the synthesis of tapentadol comprising the quantitative resolution of the racemic mixture (V) to obtain the stereoisomer of (S)-3-(dimethylamino)-2-methyl-l-(3-nitrophenyl)-propan-l-one (VII) according to the Scheme 2 below (V, VI, VII) Scheme 2 using the (2R,3R)-O,O'-dibenzoyltartaric chiral acid wherein said resolution is quantitative. The present invention also refers to some intermediate compounds of the new synthesis process of tapentadol.

  本发明涉及一种新的制备他痛定的方法，包括定量分离外消旋混合物（V）以获得立体异构体（S）-3-（二甲氨基）-2-甲基-1-（3-硝基苯基）-丙酮-1-酮（VII），如下图2所示（V，VI，VII）方案2，使用（2R，3R）-O，O'-二苯甲酰酒石酸手性酸进行分离，其中所述分离是定量的。本发明还涉及新的他痛定合成过程的一些中间化合物。
• Method for the preparation of 1-aryl-1-alkyl-3-dialkylaminopropane compounds
  申请人：Siegfried AG

  公开号：EP2674414A1

  公开（公告）日：2013-12-18

  The present invention refers to the preparation of 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane compounds, such as tapentadol, using a diastereoselective Eschenmoser-Claisen or Ireland-Claisen rearrangement.

  本发明涉及使用对映选择性的Eschenmoser-Claisen或Ireland-Claisen重排反应制备1-芳基-1-烷基-2-烷基-3-二烷基氨基丙烷化合物，例如tapentadol。
• [EN] METHOD FOR THE PREPARATION OF 1-ARYL-1-ALKYL-2-ALKYL-3-DIALKYLAMINOPROPANE COMPOUNDS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE COMPOSÉS 1-ARYL-1-ALKYL-2-ALKYL-3-DIALKYLAMINO-PROPANE
  申请人：SIEGFRIED AG

  公开号：WO2013185928A1

  公开（公告）日：2013-12-19

  The present invention refers to the preparation of 1-aryl-1-alkyl-2-alkyl-3-dialkylamino-propane compounds, such as tapentadol, using a diastereoselective Eschenmoser-Claisen or Ireland-Claisen rearrangement.

  本发明涉及使用对映选择性的Eschenmoser-Claisen或Ireland-Claisen重排反应制备1-芳基-1-烷基-2-烷基-3-二烷基氨基丙烷类化合物，如tapentadol。
• 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酚（tapentadol）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，由于苄基作为氨基取代基的存在，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偏移，并增强了化合物（VII）中立体中心定向有机金属化合物在羰基上的亲核加成的能力，以朝向所需的立体异构体。因此，这种取代允许在此步骤中获得相当大的产量增加，并因此显着提高整个替帕酚合成过程的总产量。本发明的另一个目标是通过本发明的过程获得固体形式的替帕酚自由基。本发明的另一个目标是替帕酚自由基的结晶形式I和II。本发明的另一个目标是替帕酚自由基结晶形式I和II的混合物。