2-(((2-(4-Fluorophenyl)-5,5-dimethyl-1,3-dioxan-2-YL)methyl)thio)acetic acid | 1387445-04-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(((2-(4-Fluorophenyl)-5,5-dimethyl-1,3-dioxan-2-YL)methyl)thio)acetic acid
• 英文别名: 2-[[2-(4-fluorophenyl)-5,5-dimethyl-1,3-dioxan-2-yl]methylsulfanyl]acetic acid
• CAS: 1387445-04-6
• 化学式: C₁₅H₁₉FO₄S
• 分子量: 314.378
• InChiKey: MHECDEUVSVYLTD-UHFFFAOYSA-N

物化性质

• 沸点：
  438.2±45.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(((2-(4-Fluorophenyl)-5,5-dimethyl-1,3-dioxan-2-YL)methyl)thio)acetic acid 在 N-甲基吗啉 、 titanium(IV) isopropylate 、 甲酸 、 N,O-双三甲硅基乙酰胺 、 四氯化钛 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 lithium chloride 作用下， 以 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 135.5h， 生成 (3R,4R)-1-(4-fluorophenyl)-3-[(4-fluorobenzoyl)methylthio]-4-{4-[N-(carboxymethyl)carbamoylmethoxy]phenyl}azetidin-2-one
  参考文献：
  名称：

  Selection and Development of a Route for Cholesterol Absorption Inhibitor AZD4121

  摘要：

  The development of a synthetic route to the cholesterol absorption inhibitor AZD4121 is presented. Key steps are a highly enantioselective CBS reduction, a stereospecific Staudinger reaction, an amine/lithium chloride mediated ester hydrolysis, and a resolution of a 50:50 diastereomeric mixture by recrystallization. The synthesis was accomplished in 10 linear steps, and the overall yield, when compared with the lead optimization (LO) route, was improved from 1% to 20%. All purifications of intermediates through preparative HPLC or silica gel chromatography were avoided. This was possible since many of the intermediates along the route could be used as such in the next step until an intermediate with suitable crystalline properties could be identified and purified through crystallization.

  DOI：

  10.1021/op200314z
• 作为产物：
  描述：

  ethyl 2-[2-(4-fluorophenyl)-2-oxoethyl]sulfanylacetate 在 水 、 对甲苯磺酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 19.0h， 生成 2-(((2-(4-Fluorophenyl)-5,5-dimethyl-1,3-dioxan-2-YL)methyl)thio)acetic acid
  参考文献：
  名称：

  Selection and Development of a Route for Cholesterol Absorption Inhibitor AZD4121

  摘要：

  The development of a synthetic route to the cholesterol absorption inhibitor AZD4121 is presented. Key steps are a highly enantioselective CBS reduction, a stereospecific Staudinger reaction, an amine/lithium chloride mediated ester hydrolysis, and a resolution of a 50:50 diastereomeric mixture by recrystallization. The synthesis was accomplished in 10 linear steps, and the overall yield, when compared with the lead optimization (LO) route, was improved from 1% to 20%. All purifications of intermediates through preparative HPLC or silica gel chromatography were avoided. This was possible since many of the intermediates along the route could be used as such in the next step until an intermediate with suitable crystalline properties could be identified and purified through crystallization.

  DOI：

  10.1021/op200314z

文献信息

• Selection and Development of a Route for Cholesterol Absorption Inhibitor AZD4121
  作者：Staffan Karlsson、J. Henrik Sörensen

  DOI：10.1021/op200314z

  日期：2012.4.20

  The development of a synthetic route to the cholesterol absorption inhibitor AZD4121 is presented. Key steps are a highly enantioselective CBS reduction, a stereospecific Staudinger reaction, an amine/lithium chloride mediated ester hydrolysis, and a resolution of a 50:50 diastereomeric mixture by recrystallization. The synthesis was accomplished in 10 linear steps, and the overall yield, when compared with the lead optimization (LO) route, was improved from 1% to 20%. All purifications of intermediates through preparative HPLC or silica gel chromatography were avoided. This was possible since many of the intermediates along the route could be used as such in the next step until an intermediate with suitable crystalline properties could be identified and purified through crystallization.