[2-(4-acetoxyphenyl)-6-acetoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone | 84541-33-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(4-acetoxyphenyl)-6-acetoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
• 英文别名: 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene；6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]-benzo[b]thiophene；[4-[6-acetyloxy-3-[4-(2-piperidin-1-ylethoxy)benzoyl]-1-benzothiophen-2-yl]phenyl] acetate
• CAS: 84541-33-3
• 化学式: C₃₂H₃₁NO₆S
• 分子量: 557.667
• InChiKey: PDTVFZPKYBBZIC-UHFFFAOYSA-N

物化性质

• 沸点：
  738.6±60.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [2-(4-acetoxyphenyl)-6-acetoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone 、 hydroxide 、 盐酸 以crude raloxifene hydrochloride is obtained with a purity equal to about 98%的产率得到盐酸雷洛昔芬
  参考文献：
  名称：

  PROCESS FOR CONTROLLING THE GROWTH OF A RALOXIFENE HYDROCHLORIDE CRYSTAL

  摘要：

  描述了一种控制盐酸拉洛昔芬晶体生长的方法，即控制盐酸拉洛昔芬晶体大小的方法，包括以下步骤：a）将包含结晶的盐酸拉洛昔芬、甲醇和水的质量在回流下加热约10分钟；b）将质量冷却至30-35℃；c）检查晶体大小，在步骤a）、b）和c）中重复n个周期，直到获得所需的晶体大小。

  公开号：

  US20110088613A1
• 作为产物：
  描述：

  雷洛昔芬 、 四氢呋喃 、 potassium carbonate 、 乙酸酐 在 氯化钠 、 magnesium sulfate 作用下， 以 氯仿 为溶剂， 反应 4.0h， 生成 [2-(4-acetoxyphenyl)-6-acetoxybenzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone
  参考文献：
  名称：

  Antiestrogenic and antiandrugenic benzothiophenes

  摘要：

  6-羟基-2-(4-羟基苯基)-3-[4-(2-哌啶乙氧基)苯甲酰基]苯并噻吩及其醚和酯类化合物，以及其生理上可接受的酸加盐，是有价值的抗雌激素和抗雄激素。

  公开号：

  US04418068A1

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。
• [EN] PROCESS FOR CONTROLLING THE GROWTH OF A RALOXIFENE HYDROCHLORIDE CRYSTAL<br/>[FR] PROCÉDÉ DE RÉGULATION DE LA CROISSANCE D'UN CRISTAL DE CHLORHYDRATE DE RALOXIFÈNE
  申请人：ERREGIERRE SPA

  公开号：WO2009150669A1

  公开（公告）日：2009-12-17

  A process is described for controlling the growth of a raloxifene hydrochloride crystal i.e. for the control of raloxifene hydrochloride crystal size, comprising the steps of: a) heating under reflux a mass comprising crystalline raloxifene hydrochloride, methanol and water for a time of about 10 minutes; b) cooling the mass to 30- 35°C, and c) checking the crystal size, in which steps a), b) and c) are repeated for a number of cycles n, until the desired crystal size is obtained.

  本发明描述了一种控制雷洛昔芬盐酸盐晶体生长的方法，即控制雷洛昔芬盐酸盐晶体尺寸的方法，包括以下步骤：a）将包含晶态雷洛昔芬盐酸盐，甲醇和水的物质在回流下加热约10分钟；b）将物质冷却至30-35°C；c）检查晶体尺寸。在步骤a）、b）和c）中，重复n个周期，直到获得所需的晶体尺寸。
• [EN] PROCESS FOR THE PREPARATION OF RALOXIFENE HYDROCHLORIDE<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE CHLORHYDRATE DE RALOXIFÈNE
  申请人：HETERO RESEARCH FOUNDATION

  公开号：WO2011132194A1

  公开（公告）日：2011-10-27

  The present invention provides an improved process for the preparation of α-(3- methoxyphenylthio)-4-methoxyacetophenone. The present invention also provides a process for the preparing free flowing solid of 6-methoxy-2-(4-methoxyphenyl)- benzo[b]-thiophene. The present invention further provides a process for the preparation of substantially pure 6-methoxy-2-(4-methoxyphenyl)-benzo[b]-thiophene. The present invention further provides a process for purification of raloxifene hydrochloride.

  本发明提供了一种改进的α-(3-甲氧基苯基硫)-4-甲氧基乙酮制备工艺。本发明还提供了一种制备自由流动固体6-甲氧基-2-(4-甲氧基苯基)-苯并[b]-噻吩的工艺。本发明还提供了一种制备基本纯净的6-甲氧基-2-(4-甲氧基苯基)-苯并[b]-噻吩的工艺。本发明还提供了一种纯化盐酸拉洛昔芬的工艺。
• Benzothiophene compounds and process for preparing them
  申请人：ELI LILLY AND COMPANY

  公开号：EP0062503A1

  公开（公告）日：1982-10-13

  6-Hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-[3-methylpyrrolidino]ethoxy)benzoyl]benzo[b]thiophene, its ethers and esters, and the physiologically acceptable acid addition salts thereof, and 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidi- noethoxy)benzoyl]benzo[b]-thiophene, its ethers and esters, and the physiologically acceptable acid addition salts thereof, are valuable antiestrogens and antiendrogens.

  6-羟基-2-(4-羟基苯基)-3-[4-(2-[3-甲基吡咯啉基]乙氧基)苯甲酰基]苯并噻吩，其醚和酯，以及其生理上可接受的酸盐，以及6-羟基-2-(4-羟基苯基)-3-[4-(2-哌啶基)乙氧基]苯甲酰基]苯并噻吩，其醚和酯，以及其生理上可接受的酸盐，是有价值的抗雌激素和抗雄激素。
• 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。