(S)-3-((R)-5-(4-氟苯基)-5-羟基)-4-苯基恶唑烷-2-酮 | 528565-93-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-3-((R)-5-(4-氟苯基)-5-羟基)-4-苯基恶唑烷-2-酮
• 英文名称: (4S)-3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one
• 英文别名: (R)-3-[5-(4-fluorophenyl)-5(S)-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one；3-[(5R)-(4-fluorophenyl)-5-hydroxypentanoyl]-(4S)-phenyl-1,3-oxazolidin-2-one；(S)-3-((R)-5-(4-fluorophenyl)-5-hydroxypentanoyl)-4-phenyloxazolidin-2-one
• CAS: 528565-93-7
• 化学式: C₂₀H₂₀FNO₄
• 分子量: 357.382
• InChiKey: AVAZNWOHQJYCEL-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  存储条件：2-8°C，干燥。

反应信息

• 作为反应物：
  描述：

  (S)-3-((R)-5-(4-氟苯基)-5-羟基)-4-苯基恶唑烷-2-酮 在 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以91%的产率得到(4S)-3-[5-(4-氟苯基)-1,5-二氧代戊基]-4-苯基-2-恶唑烷酮
  参考文献：
  名称：

  Lipase catalyzed kinetic resolution for the production of (S)-3-[5-(4-fluoro-phenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one: An intermediate for the synthesis of ezetimibe

  摘要：

  Efficient enzymatic methods were developed for the synthesis of (S)-3-[5-(4-fluoro-phenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one, by transesterification of (RS)-3-[5-(4-fluorophenyl)-5-hydroxypentanoyl]-4(S)-4-phenyl-1,3-oxazolidin-2-one [(R,S)-FOP alcohol] and hydrolysis of (RS)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl] pentyl acetate [(R,S)-FOP acetate] using lipase as enzyme source. The synthesized S-diastereomer is an intermediate for the potent cholesterol absorption inhibitor, ezetimibe. Among various lipases tried, Candida rugosa lipase in diisopropyl ether was best for both the reactions. Vinyl acetate was found as suitable acyl donor in transesterification reaction. A higher amount of enzyme (500 mg) was required for the transesterification of 10 mM substrate; it may be due to the enzyme denaturation by acetaldehyde formed in the reaction. The ester hydrolysis reaction worked well, excellent conversion and de were obtained at 40 degrees C, pH 7. The 300 mg enzyme hydrolyzed 120 mg (R,S)-FOP acetate with 50% conversion and 99.5% de. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2012.08.014
• 作为产物：
  描述：

  (R,S)-3-[5-(4-fluorophenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one 在 4-二甲氨基吡啶 、 Candida antarctica B lipase 、 三乙胺 、 磷脂酶B 作用下， 以 aq. phosphate buffer 、 二氯甲烷 、 异丙醚 、 甲苯 为溶剂， 反应 244.0h， 生成 (S)-3-((R)-5-(4-氟苯基)-5-羟基)-4-苯基恶唑烷-2-酮
  参考文献：
  名称：

  Lipase catalyzed kinetic resolution for the production of (S)-3-[5-(4-fluoro-phenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one: An intermediate for the synthesis of ezetimibe

  摘要：

  Efficient enzymatic methods were developed for the synthesis of (S)-3-[5-(4-fluoro-phenyl)-5-hydroxy-pentanoyl]-4-phenyl-oxazolidin-2-one, by transesterification of (RS)-3-[5-(4-fluorophenyl)-5-hydroxypentanoyl]-4(S)-4-phenyl-1,3-oxazolidin-2-one [(R,S)-FOP alcohol] and hydrolysis of (RS)-1-(4-fluorophenyl)-5-oxo-5-[(S)-2-oxo-4-phenyloxazolidin-3-yl] pentyl acetate [(R,S)-FOP acetate] using lipase as enzyme source. The synthesized S-diastereomer is an intermediate for the potent cholesterol absorption inhibitor, ezetimibe. Among various lipases tried, Candida rugosa lipase in diisopropyl ether was best for both the reactions. Vinyl acetate was found as suitable acyl donor in transesterification reaction. A higher amount of enzyme (500 mg) was required for the transesterification of 10 mM substrate; it may be due to the enzyme denaturation by acetaldehyde formed in the reaction. The ester hydrolysis reaction worked well, excellent conversion and de were obtained at 40 degrees C, pH 7. The 300 mg enzyme hydrolyzed 120 mg (R,S)-FOP acetate with 50% conversion and 99.5% de. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2012.08.014

文献信息

• Process for the preparation of 1,3,2-oxazaborolidine compounds
  申请人：Burgos Alain

  公开号：US20080139851A1

  公开（公告）日：2008-06-12

  A process is used for the preparation of 1,3,2-oxazaborolidine compounds. This process prepares compounds of formula (I) or (IA): in which: R1 is an alkyl or an aryl; and R2, R3, R4 and R5 are especially a hydrogen atom or an alkyl, wherein the following are reacted in two steps: a) a boric precursor compound with an acetal compound to give a boronate compound; and b) the boronate compound with an amino alcohol compound. This process avoids by-products and exhibits a very good stereospecificity.

  一种用于制备1,3,2-氧杂硼杂环丙烷化合物的过程。该过程制备具有化学式(I)或(IA)的化合物：其中：R1是烷基或芳基；R2、R3、R4和R5尤其是氢原子或烷基，在两个步骤中反应如下：a) 用硼前体化合物与缩醛化合物反应得到硼酸酯化合物；和b) 硼酸酯化合物与氨基醇化合物反应。该过程避免了副产物的产生，并表现出非常良好的立体特异性。
• [EN] KINETIC RESOLUTION OF (4S)-4-PHENYL-3-[5(RS)-(4-FLUOROPHENYL)-5-HYDROXYPENTANOYL] -1,3 OXAZOLIDIN 2-ONE TO (5S) ISOMER VIA LIPASE CATALYZED ENANTIOSELECTIVE ESTERIFICATION OF THE (5R) ISOMER<br/>[FR] RÉSOLUTION CINÉTIQUE DE (4S)-4-PHÉNYL-3-[5(RS)-(4-FLUOROPHÉNYL)-5-HYDROXYPENTANOYL]-1,3-OXAZOLIDIN-2-ONE EN ISOMÈRE (5S) PAR ESTÉRIFICATION ÉNANTIOSÉLECTIVE CATALYSÉE PAR UNE LIPASE DE L'ISOMÈRE (5R)
  申请人：LUPIN LTD

  公开号：WO2010113184A1

  公开（公告）日：2010-10-07

  A process for synthesis of 4S-phenyl -3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl] -1,3 oxazolidin 2-one comprising resolution of 4S-phenyl -3-[(5RS)-5-(4-fluorophenyl)-5-hydroxypentanoyl] -1,3 oxazolidin 2-one by selective esterification of 4S-phenyl -3-[(5R)-5-(4-fluorophenyl)-5-hydroxypentanoyl] -1,3 oxazolidin 2-one using appropriate esterification reagent in an organic solvent in presence of Lipase enzyme at a temperature ranging from 0° to 100°C, and further isolation.

  一种合成4S-苯基-3-[(5S)-5-(4-氟苯基)-5-羟基戊酰基]-1,3-噁唑烷-2-酮的方法，包括通过在有机溶剂中，在0°C至100°C的温度范围内，利用适当的酯化试剂在脂肪酶酶存在下，通过选择性酯化4S-苯基-3-[(5R)-5-(4-氟苯基)-5-羟基戊酰基]-1,3-噁唑烷-2-酮来实现4S-苯基-3-[(5RS)-5-(4-氟苯基)-5-羟基戊酰基]-1,3-噁唑烷-2-酮的分离。
• Process for preparing Ezetimibe intermediate by enantioselective CBS catalyzed ketone reduction with BH3–DEA prepared in situ
  作者：Blandine Bertrand、Sonia Durassier、Stéphane Frein、Alain Burgos

  DOI：10.1016/j.tetlet.2007.01.118

  日期：2007.3

  The (S) alcohol in the benzylic position of compound 2, a key intermediate in the synthesis of the cholesterol lowering agent Ezetimibe, was introduced by the (R)-MeCBS catalyzed asymmetric carbonyl reduction of ketone 1 using borane diethylaniline complex (BDEA) as the reducing agent. The latter was prepared in situ from sodium borohydride (NaBH4), diethylaniline (DEA) and dimethylsulfate (DMSO4)

  通过（R）-MeCBS以硼烷二乙基苯胺配合物（BDEA）为原料，通过（R）-MeCBS催化的酮1的不对称羰基还原反应引入了化合物2的苄基位置上的（S）醇。还原剂。后者是由硼氢化钠（NaBH 4），二乙基苯胺（DEA）和硫酸二甲酯（DMSO 4）原位制备的。从工业化角度（成本和试剂存储的稳定性）的角度来看，原位制备的BDEA比BH 3 -THF（BTHF）或BH 3的商业解决方案具有可观的优势。–DMS（BMS）。考察了关键反应参数（如试剂的添加方式，温度，溶剂，反应淬灭以及LiCl的添加）对选择性的影响。该反应已成功地用于制备依泽替米贝的关键中间体2的过程中。
• Process for preparing Ezetimibe intermediate by an acid enhanced chemo- and enantioselective CBS catalyzed ketone reduction
  作者：Xiaoyong Fu、Timothy L. McAllister、T.K. Thiruvengadam、Chou-Hong Tann、Dan Su

  DOI：10.1016/s0040-4039(02)02700-4

  日期：2003.1

  The S alcohol in the benzylic position of compound 2, a key feature of a novel cholesterol lowering agent Ezetimibe, was introduced by the (R)-MeCBS catalyzed asymmetric carbonyl reduction of ketone 1 using borane tetrahydrofuran complex (BTHF) as the reducing agent. The chemo- and enantioselectivity was dramatically enhanced by using an acid as a scavenger of the stabilizer sodium borohydride present

  化合物2的苄基位置上的S醇是新型降胆固醇剂Ezetimibe的关键特征，是通过（R）-MeCBS催化的硼烷四氢呋喃配合物（BTHF）还原为酮1的不对称羰基还原反应而引入的。通过使用酸作为市售纯BTHF中存在的稳定剂硼氢化钠的清除剂，可以显着提高化学和对映选择性。已经检验了关键反应参数（例如试剂的添加方式，温度，酸以及水含量）对选择性的影响。该反应已成功地用于商业过程中，用于制备关键中间体2 为Ezetimibe。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF EZETIMIBE INTERMEDIATES<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION D'INTERMÉDIAIRES D'ÉZÉTIMIBE
  申请人：PHARMATHEN SA

  公开号：WO2015039675A1

  公开（公告）日：2015-03-26

  The present invention provides a novel process for the preparation of compounds useful as intermediates for the production of Ezetimibe.

  本发明提供了一种新颖的方法，用于制备作为Ezetimibe生产中间体有用的化合物。