[4-[6-Hydroxy-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophen-2-yl]phenyl] methanesulfonate | 1100049-66-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-[6-Hydroxy-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophen-2-yl]phenyl] methanesulfonate
• 英文别名: [4-[6-hydroxy-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophen-2-yl]phenyl] methanesulfonate
• CAS: 1100049-66-8
• 化学式: C₂₉H₂₉NO₆S₂
• 分子量: 551.684
• InChiKey: HMIKBYYMKYYKCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  6-methanesulfonyloxy-2-(4-methanesulfonyloxyphenyl)-3-[4-(2-piperidinoethoxy)-benzoyl]benzo[b]thiophene 在 sodium hydroxide 、 水 、 溶剂黄146 、 氨 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 14.33h， 生成 [2-(4-Hydroxyphenyl)-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophen-6-yl] methanesulfonate 、 [4-[6-Hydroxy-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophen-2-yl]phenyl] methanesulfonate 、 雷洛昔芬
  参考文献：
  名称：

  [EN] A PROCESS FOR THE PREPARATION OF 6-HYDROXY-2-(4-HYDROXYPHENYL)-3-[4-(2-PIPERIDINO ETHOXY) BENZOYL]BENZO[B]THIOPHENE
  [FR] PROCÉDÉ DE PRÉPARATION DE 6-HYDROXY-2-(4-HYDROXYPHÉNYL)-3-[4-(2-PIPÉRIDINOÉTHOXY)BENZOYL]BENZO[B]THIOPHÈNE

  摘要：

  公开号：

  WO2009008000A3

文献信息

• [EN] PROCESS FOR PREPARING RALOXIFENE HYDROCHLORIDE<br/>[FR] PROCEDE POUR PREPARER DE L'HYDROCHLORURE DE RALOXIFENE
  申请人：ERREGIERRE SPA

  公开号：WO2005003116A1

  公开（公告）日：2005-01-13

  Process for preparing raloxifene hydrochloride with a purity greater than 98% and low aluminium content comprising the following stages a) demethylation of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene in pyridine and hydrochloric acid to obtain 6-hydroxy­2-(4-hydroxyphenyl)benzo[b]thiophene in pyridine hydrochloride, b) acetylation of 6-hydroxy-2-(4­hydroxyphonyl)benzo[b]thiophene with an acetylating agent to obtain the corresponding 6-acetoxy-2-(4 acetoxyphenyl)benzo[b]thiophene, c) acylation of 6-acetoxy-2-(4-acetoxyphonyl)benzo[b]thlophene with 4-(2 piperidinoethoxy)benzoylchloride hydrochloride with aluminium trichloride in halogenated solvent to obtain 6-acetoxy-2-(4­acetoxyphenyl)-3-[4-(2 piperidinoethoxy)benzoyl]-benzo[b]thiophene, d) hydrolysis of 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyll benzo[b]thiophene according to the following operating conditions: dl) treatment of 6-acetoxy-2-(4-acetoxyphonyl)-3-[4-(2­piperidinoethoxy)benzoyl]benzo[b]thiophene with alkaline hydroxide in alcohol solvent, d2) acidification of the product obtained in the preceding stage (dl) with a strong acid, to obtain the corresponding raloxifene salt with the strong acid, characterised in that the strong acid used in stage (d2) is concentrated hydrochloric acid.

  制备纯度大于98％且铝含量低的盐酸拉洛昔芬的过程包括以下阶段：a）在吡啶和盐酸中去甲基化6-甲氧基-2-（4-甲氧基苯基）苯并[b]噻吩，以获得吡啶盐酸中的6-羟基-2-（4-羟基苯基）苯并[b]噻吩，b）用乙酰化试剂对6-羟基-2-（4-羟基苯基）苯并[b]噻吩进行乙酰化，以获得相应的6-乙酰氧基-2-（4-乙酰氧基苯基）苯并[b]噻吩，c）用卤代溶剂中的氯化铝三和4-（2-哌啶乙氧基）苯甲酰氯盐酸酰化6-乙酰氧基-2-（4-乙酰氧基苯基）苯并[b]噻吩，以获得6-乙酰氧基-2-（4-乙酰氧基苯基）-3- [4-（2-哌啶乙氧基）苯甲酰] -苯并[b]噻吩，d）根据以下操作条件水解6-乙酰氧基-2-（4-乙酰氧基苯基）-3- [4-（2-哌啶乙氧基）苯甲酰] -苯并[b]噻吩：dl）在醇溶剂中用碱性氢氧化物处理6-乙酰氧基-2-（4-乙酰氧基苯基）-3- [4-（2-哌啶乙氧基）苯甲酰] -苯并[b]噻吩，d2）用强酸酸化前一阶段（dl）中获得的产物，以获得强酸的相应拉洛昔芬盐，其特征在于阶段（d2）中使用的强酸为浓盐酸。
• Process for preparing raloxifene hydrochloride
  申请人：Ferrari Massimo

  公开号：US20070100147A1

  公开（公告）日：2007-05-03

  Process for preparing raloxifene hydrochloride with a purity greater than 98% and low aluminium content comprising the following stages a) demethylation of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene in pyridine and hydrochloric acid to obtain 6-hydroxy2-(4-hydroxyphenyl)benzo[b]thiophene in pyridine hydrochloride, b) acetylation of 6-hydroxy-2-(4hydroxyphonyl)benzo[b]thiophene with an acetylating agent to obtain the corresponding 6-acetoxy-2-(4 acetoxyphenyl)benzo[b]thiophene, c) acylation of 6-acetoxy-2-(4-acetoxyphonyl)benzo[b]thiophene with 4-(2 piperidinoethoxy)benzoylchloride hydrochloride with aluminium trichloride in halogenated solvent to obtain 6-acetoxy-2-(4acetoxyphenyl)-3-[4-(2 piperidinoethoxy)benzoyl]-benzo[b]thiophene, d) hydrolysis of 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyll benzo[b]thiophene according to the following operating conditions: d1) treatment of 6-acetoxy-2-(4-acetoxyphonyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene with alkaline hydroxide in alcohol solvent, d2) acidification of the product obtained in the preceding stage (d1) with a strong acid, to obtain the corresponding raloxifene salt with the strong acid, characterised in that the strong acid used in stage (d2) is concentrated hydrochloric acid.

  制备纯度大于98％且铝含量低的盐酸拉洛昔芬的过程包括以下步骤：a）在吡啶和盐酸中去甲基化6-甲氧基-2-（4-甲氧基苯基）苯并[b]噻吩，以获得吡啶盐酸6-羟基-2-（4-羟基苯基）苯并[b]噻吩，b）用乙酰化试剂乙酰化6-羟基-2-（4-羟基苯基）苯并[b]噻吩，以获得相应的6-乙酰氧基-2-（4-乙酰氧基苯基）苯并[b]噻吩，c）在卤代溶剂中用铝三氯化物和4-（2-哌啶乙氧基）苯甲酰氯盐酸盐酰化6-乙酰氧基-2-（4-乙酰氧基苯基）-3-[4-（2-哌啶乙氧基）苯甲酰]-苯并[b]噻吩，d）根据以下操作条件水解6-乙酰氧基-2-（4-乙酰氧基苯基）-3-[4-（2-哌啶乙氧基）苯甲酰]-苯并[b]噻吩：d1）在醇溶剂中用碱性氢氧化物处理6-乙酰氧基-2-（4-乙酰氧基苯基）-3-[4-（2-哌啶乙氧基）苯甲酰]-苯并[b]噻吩，d2）用强酸酸化前一阶段（d1）中获得的产物，以获得与强酸的相应盐酸拉洛昔芬，其特征在于在第（d2）阶段使用的强酸是浓盐酸。
• PROCESS FOR PREPARING RALOXIFENE HYDROCHLORIDE
  申请人：ERREGIERRE S.p.A.

  公开号：EP1641773A1

  公开（公告）日：2006-04-05
• [EN] A PROCESS FOR THE PREPARATION OF 6-HYDROXY-2-(4-HYDROXYPHENYL)-3-[4-(2-PIPERIDINO ETHOXY) BENZOYL]BENZO[B]THIOPHENE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 6-HYDROXY-2-(4-HYDROXYPHÉNYL)-3-[4-(2-PIPÉRIDINOÉTHOXY)BENZOYL]BENZO[B]THIOPHÈNE
  申请人：SUN PHARMACEUTICAL IND LTD

  公开号：WO2009008000A3

  公开（公告）日：2011-08-11