Cyclobutanecarboxylic acid, 1-(4-chlorophenyl)-3-hydroxy-3-methyl-, methyl ester, trans- | 1370618-04-4

• 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: Cyclobutanecarboxylic acid, 1-(4-chlorophenyl)-3-hydroxy-3-methyl-, methyl ester, trans-
• 英文别名: methyl 1-(4-chlorophenyl)-3-hydroxy-3-methylcyclobutane-1-carboxylate
• CAS: 1370618-04-4
• 化学式: C₁₃H₁₅ClO₃
• 分子量: 254.713
• InChiKey: CYOXCIXAZSWAPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Cyclobutanecarboxylic acid, 1-(4-chlorophenyl)-3-hydroxy-3-methyl-, methyl ester, trans- 在 盐酸 、 lithium hydroxide monohydrate 、 二苯基膦叠氮化物 、 水 、 potassium acetate 、 sodium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 35.83h， 生成 tert-butyl {trans-3-Hydroxy-3-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutyl}carbamate
  参考文献：
  名称：

  Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor

  摘要：

  The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions.

  DOI：

  10.1021/op300031r
• 作为产物：
  描述：

  methyl cis-1-(4-chlorophenyl)-3-hydroxycyclobutanecarboxylate 在 sodium hypochlorite 、 potassium hydrogencarbonate 、 potassium bromide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 3.75h， 生成 Cyclobutanecarboxylic acid, 1-(4-chlorophenyl)-3-hydroxy-3-methyl-, methyl ester, trans- 、 Cyclobutanecarboxylic acid, 1-(4-chlorophenyl)-3-hydroxy-3-methyl-, methyl ester, trans-
  参考文献：
  名称：

  Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor

  摘要：

  The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions.

  DOI：

  10.1021/op300031r