tert-butyl (3R)-3-[2-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-methylpropyl]-4-methoxyphenyl]-3-(6-butyl-3-formylpyridin-2-yl)propanoate | 203380-38-5

• 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: tert-butyl (3R)-3-[2-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-methylpropyl]-4-methoxyphenyl]-3-(6-butyl-3-formylpyridin-2-yl)propanoate
• CAS: 203380-38-5
• 化学式: C₃₄H₅₃NO₅Si
• 分子量: 583.884
• InChiKey: JQCUZJFDTOPANL-QABMSTFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.31
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-溴-1,2-亚甲二氧基苯 、 tert-butyl (3R)-3-[2-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-methylpropyl]-4-methoxyphenyl]-3-(6-butyl-3-formylpyridin-2-yl)propanoate 在 magnesium 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 5.0h， 生成 tert-butyl (3R)-3-[3-[(R)-1,3-benzodioxol-5-yl(hydroxy)methyl]-6-butylpyridin-2-yl]-3-[2-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-methylpropyl]-4-methoxyphenyl]propanoate 、
  参考文献：
  名称：

  Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist

  摘要：

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.

  DOI：

  10.1021/jo991292t
• 作为产物：
  描述：

  tert-butyl (6-butyl-3-formylpyridin-2-yl)acrylate 在 正丁基锂 、 溶剂黄146 作用下， 以 正己烷 、 甲苯 为溶剂， 反应 18.0h， 生成 tert-butyl (3R)-3-[2-[(2S)-3-[tert-butyl(dimethyl)silyl]oxy-2-methylpropyl]-4-methoxyphenyl]-3-(6-butyl-3-formylpyridin-2-yl)propanoate
  参考文献：
  名称：

  Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist

  摘要：

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.

  DOI：

  10.1021/jo991292t