(alphaS)-4-氟-alpha-(2-碘乙基)苯甲醇 | 926657-23-0

• 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: (alphaS)-4-氟-alpha-(2-碘乙基)苯甲醇
• 中文别名: (ALPHAS)-4-氟-ALPHA-(2-碘乙基)苯甲醇
• 英文名称: (S)-1-(4-Fluoro-phenyl)-3-iodo-propan-1-ol
• 英文别名: (S)-1-(4-fluorophenyl)-3-iodopropan-1-ol；(1S)-1-(4-fluorophenyl)-3-iodopropan-1-ol
• CAS: 926657-23-0
• 化学式: C₉H₁₀FIO
• 分子量: 280.081
• InChiKey: UYQBOULHLSGQPI-VIFPVBQESA-N

物化性质

• 熔点：
  70-71℃
• 沸点：
  297.1±35.0 °C(Predicted)
• 密度：
  1.749

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (alphaS)-4-氟-alpha-(2-碘乙基)苯甲醇 在 palladium on activated charcoal 氢氧化钾 、 氢气 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 3R-(4-fluoro-phenyl)-1-[3-(4-fluoro-phenyl)-3S-hydroxy-propyl]-4R-(4-hydroxy-phenyl)-azetidin-2-one
  参考文献：
  名称：

  Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions

  摘要：

  The underlying principle of drug design in this paper is that the maximum retention of the functional groups that exist in the marketed drug would provide a higher probability for comparable safety while the conformational changes in the newly created analogs should not constitute a significant structural variation to adversely affect biological activity. Four individual isomers of backbone re-organized ezetimibe analogs were designed and synthesized. Their effects on the cholesterol levels in rat serum were evaluated by a high-cholesterol and high-fat diet feeding experiment. All the new analogs showed significant effect in lowering the levels of total cholesterol in serum. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.078
• 作为产物：
  描述：

  3'-氯-4-氟苯丙酮 在 dimethyl sulfide borane 、 chiral (R)-CBS catalyst 、 sodium iodide 作用下， 生成 (alphaS)-4-氟-alpha-(2-碘乙基)苯甲醇
  参考文献：
  名称：

  Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions

  摘要：

  The underlying principle of drug design in this paper is that the maximum retention of the functional groups that exist in the marketed drug would provide a higher probability for comparable safety while the conformational changes in the newly created analogs should not constitute a significant structural variation to adversely affect biological activity. Four individual isomers of backbone re-organized ezetimibe analogs were designed and synthesized. Their effects on the cholesterol levels in rat serum were evaluated by a high-cholesterol and high-fat diet feeding experiment. All the new analogs showed significant effect in lowering the levels of total cholesterol in serum. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.078

文献信息

• [EN] PROCESS FOR PREPARING AN ANTI-HYPERCHOLESTEROLEMIC COMPOUND<br/>[FR] PROCÉDÉ DE PRÉPARATION D'UN COMPOSÉ ANTI-HYPERCHOLESTÉROLÉMIANT
  申请人：MERCK & CO INC

  公开号：WO2009054887A1

  公开（公告）日：2009-04-30

  The present invention relates to a process for preparing inhibitors of cholesterol absorption of Formula II: II and the pharmaceutically acceptable salts and esters thereof, employing a metal-catalyzed dynamic kinetic resolution (DKR) asymmetric transfer hydrogenation (ATH) reaction of racemic acyclic ß-ketoamide bearing a-substituted aliphatic side chain (Intermediate A) and subsequent cyclization of the resulting b-hydroxyamide product (Intermediate B), followed by a synthesis involving two consecutive cross-coupling reactions.

  本发明涉及一种制备胆固醇吸收抑制剂的方法，该方法涉及使用金属催化的动态动力学分辨（DKR）不对称转移氢化（ATH）反应，对具有α-取代脂肪侧链的无光学活性β-酮酰胺（中间体A）进行环化，得到b-羟基酰胺产物（中间体B），然后通过两个连续的交叉偶联反应进行合成。
• Dynamic Kinetic Resolution: Asymmetric Transfer Hydrogenation of α-Alkyl-Substituted β-Ketoamides
  作者：John Limanto、Shane W. Krska、Benjamin T. Dorner、Enrique Vazquez、Naoki Yoshikawa、Lushi Tan

  DOI：10.1021/ol902715d

  日期：2010.2.5

  Dynamic kinetic resolution (deracemization) of various alpha-alkyl-substituted beta-ketoamides 1 via asymmetric transfer hydrogenation proceeded efficiently to give the corresponding syn-beta-hydroxy amides 3 in high diastereo- and enantioselectivities. Specifically, subjection of 1 to HCO2H and Et3N in the presence of 0.5-1 mol % of pentafluorobenzenesulfonyl-DPEN-Ru catalyst 2b at 30-40 degrees C in either PhCH3 or CH2Cl2 generated the syn-hydroxy product 3 selectively in 15-33:1 dr, 93-97% ee, and 75-88% isolated yields.