3-hydroxyestra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide | 151313-07-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3-hydroxyestra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide
• 英文别名: (8S,9S,13S,14S,17S)-N-tert-butyl-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-17-carboxamide
• CAS: 151313-07-4
• 化学式: C₂₃H₃₃NO₂
• 分子量: 355.521
• InChiKey: BQFSTNWHKOWESN-MZSWFSNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-hydroxyestra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide 在 palladium diacetate 焦硫酰氟 、 1,3-双(二苯基膦)丙烷 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， -8.0~75.0 ℃ 、48.26 kPa 条件下， 反应 3.0h， 生成 3-(methoxycarbonyl)estra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide
  参考文献：
  名称：

  A Novel, Practical Synthesis of Estra-1,3,5(10)-triene-3,17.beta.-dicarboxylic Acid 17-tert-Butylamide (SK&F 105656) from Estrone, via a Palladium-Catalyzed Methoxycarbonylation of a 3-Fluorosulfonate

  摘要：

  The title compound was prepared in nine steps from estrone in 22% overall yield. Each step was performed on a 50-150 gal scale and 3.5 kg of the title compound was prepared. Estrone was converted to its 3-methanesulfonate with methanesulfonyl chloride. The 17-cyanohydrin was prepared using trimethylsilyl cyanide. Dehydration with phosphorus oxychloride/pyridine followed by Pd/C-catalyzed hydrogenation gave the 17 beta-cyano-3-hydroxyestra-1,3,5(10), 16-tetraen-3-yl methanesulfonate derivative stereoselectively. Hydrolysis with sodium hydroxide in ethylene glycol gave a 3/1 beta/alpha mixture of l7-carboxylic acid isomers. Reaction with Vilsmeier reagent and quenching into tert-butylamine, followed by selective crystallization, yielded the desired 3-hydroxyestra-1,3,5(10)-triene-17 beta-carboxylic acid tert-butylamide. Reaction with fluorosulfonic anhydride yielded the S-fluorosulfonate. Palladium-catalyzed carbonylation in the presence of methanol gave the S-carboxylic acid methyl ester, which was saponified to yield SK&F 105656.

  DOI：

  10.1021/jo00101a028
• 作为产物：
  描述：

  雌酚酮 在 palladium on activated charcoal 、 zinc(II) iodide 吡啶 、 sodium hydroxide 、 草酰氯 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 乙二醇 为溶剂， 10.0~160.0 ℃ 、179.27 kPa 条件下， 反应 31.5h， 生成 3-hydroxyestra-1,3,5(10)-triene-17β-carboxylic acid tert-butylamide
  参考文献：
  名称：

  A Novel, Practical Synthesis of Estra-1,3,5(10)-triene-3,17.beta.-dicarboxylic Acid 17-tert-Butylamide (SK&F 105656) from Estrone, via a Palladium-Catalyzed Methoxycarbonylation of a 3-Fluorosulfonate

  摘要：

  The title compound was prepared in nine steps from estrone in 22% overall yield. Each step was performed on a 50-150 gal scale and 3.5 kg of the title compound was prepared. Estrone was converted to its 3-methanesulfonate with methanesulfonyl chloride. The 17-cyanohydrin was prepared using trimethylsilyl cyanide. Dehydration with phosphorus oxychloride/pyridine followed by Pd/C-catalyzed hydrogenation gave the 17 beta-cyano-3-hydroxyestra-1,3,5(10), 16-tetraen-3-yl methanesulfonate derivative stereoselectively. Hydrolysis with sodium hydroxide in ethylene glycol gave a 3/1 beta/alpha mixture of l7-carboxylic acid isomers. Reaction with Vilsmeier reagent and quenching into tert-butylamine, followed by selective crystallization, yielded the desired 3-hydroxyestra-1,3,5(10)-triene-17 beta-carboxylic acid tert-butylamide. Reaction with fluorosulfonic anhydride yielded the S-fluorosulfonate. Palladium-catalyzed carbonylation in the presence of methanol gave the S-carboxylic acid methyl ester, which was saponified to yield SK&F 105656.

  DOI：

  10.1021/jo00101a028

文献信息

• A Novel, Practical Synthesis of Estra-1,3,5(10)-triene-3,17.beta.-dicarboxylic Acid 17-tert-Butylamide (SK&F 105656) from Estrone, via a Palladium-Catalyzed Methoxycarbonylation of a 3-Fluorosulfonate
  作者：Michael A. McGuire、Edmund Sorenson、Franklin W. Owings、Theodore M. Resnick、Margaret Fox、Neil H. Baine

  DOI：10.1021/jo00101a028

  日期：1994.11

  The title compound was prepared in nine steps from estrone in 22% overall yield. Each step was performed on a 50-150 gal scale and 3.5 kg of the title compound was prepared. Estrone was converted to its 3-methanesulfonate with methanesulfonyl chloride. The 17-cyanohydrin was prepared using trimethylsilyl cyanide. Dehydration with phosphorus oxychloride/pyridine followed by Pd/C-catalyzed hydrogenation gave the 17 beta-cyano-3-hydroxyestra-1,3,5(10), 16-tetraen-3-yl methanesulfonate derivative stereoselectively. Hydrolysis with sodium hydroxide in ethylene glycol gave a 3/1 beta/alpha mixture of l7-carboxylic acid isomers. Reaction with Vilsmeier reagent and quenching into tert-butylamine, followed by selective crystallization, yielded the desired 3-hydroxyestra-1,3,5(10)-triene-17 beta-carboxylic acid tert-butylamide. Reaction with fluorosulfonic anhydride yielded the S-fluorosulfonate. Palladium-catalyzed carbonylation in the presence of methanol gave the S-carboxylic acid methyl ester, which was saponified to yield SK&F 105656.