3-(4-acetyl-2-methoxyphenoxy)propyl 4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine-1-carboxylate | 1400590-28-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(4-acetyl-2-methoxyphenoxy)propyl 4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine-1-carboxylate
• 英文别名: 3-(4-Acetyl-2-methoxyphenoxy)propyl 4-(6-fluoro-1,2-benzoxazol-3-yl)piperidine-1-carboxylate
• CAS: 1400590-28-4
• 化学式: C₂₅H₂₇FN₂O₆
• 分子量: 470.498
• InChiKey: SDSIXAKCZLIJSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  91.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  香草乙酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(4-acetyl-2-methoxyphenoxy)propyl 4-(6-fluorobenzo[d]isoxazol-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Improved and Efficient Process for the Production of Highly Pure Iloperidone: A Psychotropic Agent

  摘要：

  The present work describes an improved and highly efficient process for the synthesis of iloperidone (1), an antipsychotic agent, which is free from potential impurities. The synthesis comprises N-alkylation of 1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone (4) with 6-fluoro-3-piperidin-4-yl-1,2-benzisoxazole hydrochloride (5) in a mixture of water and heptane as solvent and sodium hydroxide as a base in the presence of tetrabutylammonium bromide as a phase transfer catalyst to yield iloperidone (1) with a yield of around 95% and a purity of 99.80% by HPLC. The present work also describes the optimization details performed to achieve the process attributes responsible for high yield and purity.

  DOI：

  10.1021/op400335p

文献信息

• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF ILOPERIDONE<br/>[FR] AMÉLIORATION DE PROCÉDÉ D'ÉLABORATION D'ILOPÉRIDONE
  申请人：ORCHID CHEMICALS & PHARM LTD

  公开号：WO2011055188A1

  公开（公告）日：2011-05-12

  The present invention relates to an improved process for the preparation of Iloperidone of formula (I). Further the present invention also provides a novel polymorph of acid addition salts of Iloperidone of formula (I). (I)

  本发明涉及一种改进的制备公式（I）的依洛噻酮的方法。此外，本发明还提供了一种新型的依洛噻酮盐酸盐多晶形式。
• [EN] A PROCESS FOR THE PREPARATION OF ILOPERIDONE AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'IOPÉRIDONE ET SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELLE-CI
  申请人：ARCH PHARMALABS LTD

  公开号：WO2012153341A1

  公开（公告）日：2012-11-15

  The present invention relates to a new process for the preparation of 1- [4-[3-[4-(6-fluoro- 1,2-benzisoxazol-3-yl)- l-piperidinyl]propoxy]-3- methoxyphenyl]- ethanone (Iloperidone) and salts thereof. The synthetic process comprises the reaction between itself 6-fluoro-3-(4- piperidinyl)-l,2-benzisoxazole of formula II as base rather than use of its hydrochloride as mostly reported in prior art and l-[4-(3- chloropropoxy)-3-methoxyphenyl]ethanone of formula III. This invention also relates to a process for the preparation of carbonated iloperidone; an impurity of the formula IV formed during the condensation of the compound of formula II and compound of formula III in presence of a base, method of its isolation and characterization thereof, as well as its use as a reference standard and reference marker in analytical department while evaluating the purity profile of iloperidone. Formula (I) (II) (III)

  本发明涉及一种制备1-[4-[3-[4-(6-氟-1,2-苯并异噁唑-3-基)-1-哌啶基]丙氧基]-3-甲氧基苯基]-乙酮（Iloperidone）及其盐的新工艺。该合成工艺包括将其自身6-氟-3-(4-哌啶基)-1,2-苯并异噁唑（II式）作为碱而不是使用其盐酸盐，这在先前的文献中大多数报道，以及I-[4-(3-氯丙氧基)-3-甲氧基苯基]乙酮（III式）之间的反应。本发明还涉及一种制备碳酸化Iloperidone的方法；在存在碱的情况下，通过II式化合物和III式化合物的缩合反应形成的IV式杂质的制备方法，其分离和表征的方法，以及在评估Iloperidone纯度剖面时作为参考标准和参考标记在分析部门中使用。式（I）（II）（III）
• [EN] A PROCESS FOR PREPARATION OF ILOPERIDONE AND AMORPHOUS CO- PRECIPITATE OF ILOPERIDONE WITH PHARMACEUTICALLY ACCEPTABLE EXCIPIENT<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'ILOPÉRIDONE ET DE COPRÉCIPITÉ AMORPHE D'ILOPÉRIDONE AVEC UN EXCIPIENT PHARMACEUTIQUEMENT ACCEPTABLE
  申请人：MEGAFINE PHARMA P LTD

  公开号：WO2012123963A2

  公开（公告）日：2012-09-20

  A process for preparation of iloperidone wherein 1-(4-(3-chloropropoxy-3- methoxyphenyl)ethanone is reacted with 6-fluoro-3-piperidin-4-yl-1,2 benzisoxazole hydrochloride in a biphasic solvent system in presence of an inorganic base and a phase transfer catalyst. Further, process for preparation of an amorphous co-precipitate of iloperidone or its acid addition salt along with pharmaceutically acceptable excipient is proposed. Further, the present invention also relates to a co-precipitate of amorphous form of iloperidone along with pharmaceutically acceptable excipients.
• Improved and Efficient Process for the Production of Highly Pure Iloperidone: A Psychotropic Agent
  作者：Pavankumar V. Solanki、Sekhar Babu Uppelli、Bhushan S. Pandit、Vijayavitthal T. Mathad

  DOI：10.1021/op400335p

  日期：2014.2.21

  The present work describes an improved and highly efficient process for the synthesis of iloperidone (1), an antipsychotic agent, which is free from potential impurities. The synthesis comprises N-alkylation of 1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone (4) with 6-fluoro-3-piperidin-4-yl-1,2-benzisoxazole hydrochloride (5) in a mixture of water and heptane as solvent and sodium hydroxide as a base in the presence of tetrabutylammonium bromide as a phase transfer catalyst to yield iloperidone (1) with a yield of around 95% and a purity of 99.80% by HPLC. The present work also describes the optimization details performed to achieve the process attributes responsible for high yield and purity.