isopropyl 3-(1-methanesulfonylpiperidin-4-yl)propenoate | 937282-79-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: isopropyl 3-(1-methanesulfonylpiperidin-4-yl)propenoate
• 英文别名: 3-(1-Methanesulfonyl-piperidin-4-yl)-acrylic acid isopropyl ester；propan-2-yl 3-(1-methylsulfonylpiperidin-4-yl)prop-2-enoate
• CAS: 937282-79-6
• 化学式: C₁₂H₂₁NO₄S
• 分子量: 275.369
• InChiKey: SNNFLRDFJJCFJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  isopropyl 3-(1-methanesulfonylpiperidin-4-yl)propenoate 、 3,5-二氟苯硼酸 在 chloro(1,5-cyclooctadiene)rhodium(I) dimer 、 potassium carbonate 、 (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 0.25h， 以75%的产率得到(R)-iso-propyl 3-(3,5-difluorophenyl)-3-(1-(methylsulfonyl)piperidine-4-yl)propanoate
  参考文献：
  名称：

  Development of an Enantioselective, Kilogram-Scale, Rhodium-Catalysed 1,4-Addition

  摘要：

  A rhodium-catalysed 1,4-addition of an arylboron species to an alpha,beta-unsaturated ester was the key chirality-inducing step in the synthesis of an API. We describe herein the development of this chemistry, including optimization of reagent charges, reaction conditions, and metal recovery, in order to allow manufacture at multikilogram scale. A key result was the unexpected discovery that the use of a minimal quantity of an alcohol, rather than water, reduces the extent of rhodium-mediated protodeboronation of the boron species. This allowed the charge of this expensive reagent to be significantly reduced. Furthermore, the use of an alcohol instead of water avoided the agglomeration of the inorganic base present in the reaction, making the process more robust and operationally simpler. To our knowledge this is the first time that this type of C-C bond-forming chemistry has been used in a multikilo manufacture.

  DOI：

  10.1021/op700246g
• 作为产物：
  描述：

  1-(甲基磺酰基)-4-哌啶羧酸乙酯 在 哌啶 、 lithium aluminium tetrahydride 、 草酰氯 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 0.67h， 生成 isopropyl 3-(1-methanesulfonylpiperidin-4-yl)propenoate
  参考文献：
  名称：

  Development of an Enantioselective, Kilogram-Scale, Rhodium-Catalysed 1,4-Addition

  摘要：

  A rhodium-catalysed 1,4-addition of an arylboron species to an alpha,beta-unsaturated ester was the key chirality-inducing step in the synthesis of an API. We describe herein the development of this chemistry, including optimization of reagent charges, reaction conditions, and metal recovery, in order to allow manufacture at multikilogram scale. A key result was the unexpected discovery that the use of a minimal quantity of an alcohol, rather than water, reduces the extent of rhodium-mediated protodeboronation of the boron species. This allowed the charge of this expensive reagent to be significantly reduced. Furthermore, the use of an alcohol instead of water avoided the agglomeration of the inorganic base present in the reaction, making the process more robust and operationally simpler. To our knowledge this is the first time that this type of C-C bond-forming chemistry has been used in a multikilo manufacture.

  DOI：

  10.1021/op700246g

文献信息

• Process for Preparing Beta-(Fluorophenyl)-Propanoate Ester Derivatives
  申请人：Oldfield John

  公开号：US20090111993A1

  公开（公告）日：2009-04-30

  A process for preparing a compound of formula (I) comprising reacting a compound of formula (II) with a fluorinated boron species of formula (III) in the presence of: an alcohol; a rhodium (I) pre-catalyst species; a suitable ligand that binds to the rhodium (I) pre-catalyst species to form a catalyst complex; a base; and, a suitable solvent; the process being carried out at a temperature in the range 40 to 110° C. The compounds of formula (I) are useful in the preparation of pharmaceutically active compounds.

  一种制备式（I）化合物的方法，包括在存在以下条件下将式（II）化合物与式（III）的氟硼基物质反应：一种醇；一种铑（I）预催化剂物种；一种适当的配体，该配体与铑（I）预催化剂物种结合形成催化剂复合物；一种碱；和一种适当的溶剂；该过程在40至110℃的温度范围内进行。式（I）化合物在制备药物活性化合物方面有用。
• Chemical Compound
  申请人：Faull Alan Wellington

  公开号：US20080139612A1

  公开（公告）日：2008-06-12

  The present invention relates to 4-[3-(1,1-difluoroethyl)-5-methyl-4H-1,2,4-triazol-4-yl]-1-(1R,3R)-3-(3,5-difluorophenyl)-1-methyl-3-[1-(methylsulfonyl)piperidin-4-yl]propyl}piperidine (I): or a pharmaceutically acceptable salt thereof, as well as processes for the preparation of this compound and its use in the treatment of CCR5 disease states.

  本发明涉及4-[3-(1,1-二氟乙基)-5-甲基-4H-1,2,4-三唑-4-基]-1-(1R,3R)-3-(3,5-二氟苯基)-1-甲基-3-[1-(甲基磺酰基)哌啶-4-基]丙基}哌啶(I)或其药学上可接受的盐，以及制备该化合物的方法和其在治疗CCR5疾病状态中的用途。
• Piperidine Derivative Used for Treating Chemokine Receptor 5 Mediated Diseases
  申请人：Faull Alan Wellington

  公开号：US20100099708A1

  公开（公告）日：2010-04-22

  The present invention relates to 4-[3-(1,1-difluoroethyl)-5-methyl-4H-1,2,4-triazol-4-yl]-1-(1R,3R)-3-(3,5-difluorophenyl)-1-methyl-3-[1-(methylsulfonyl)ρiperidin-4-yl]propyl}piperidine formula (I): or a pharmaceutically acceptable salt thereof, as well as processes for the preparation of this compound and its use in the treatment of CCR5 disease states.

  本发明涉及4-[3-(1,1-二氟乙基)-5-甲基-4H-1,2,4-三唑-4-基]-1-(1R,3R)-3-(3,5-二氟苯基)-1-甲基-3-[1-(甲基磺酰基)哌啶-4-基]丙基}哌啶式(I)或其药学上可接受的盐，以及制备该化合物的方法和其在治疗CCR5疾病状态中的应用。
• WO2007/57643
  申请人：——

  公开号：——

  公开（公告）日：——
• Development of an Enantioselective, Kilogram-Scale, Rhodium-Catalysed 1,4-Addition
  作者：Sally Brock、David R. J. Hose、Jonathan D. Moseley、Alexandra J. Parker、Ian Patel、Andrew J. Williams

  DOI：10.1021/op700246g

  日期：2008.5.1

  A rhodium-catalysed 1,4-addition of an arylboron species to an alpha,beta-unsaturated ester was the key chirality-inducing step in the synthesis of an API. We describe herein the development of this chemistry, including optimization of reagent charges, reaction conditions, and metal recovery, in order to allow manufacture at multikilogram scale. A key result was the unexpected discovery that the use of a minimal quantity of an alcohol, rather than water, reduces the extent of rhodium-mediated protodeboronation of the boron species. This allowed the charge of this expensive reagent to be significantly reduced. Furthermore, the use of an alcohol instead of water avoided the agglomeration of the inorganic base present in the reaction, making the process more robust and operationally simpler. To our knowledge this is the first time that this type of C-C bond-forming chemistry has been used in a multikilo manufacture.