(2R)-2-[3,5-bis(prop-2-enoxy)phenyl]-2-hydroxyacetonitrile | 189683-92-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2R)-2-[3,5-bis(prop-2-enoxy)phenyl]-2-hydroxyacetonitrile
• CAS: 189683-92-9
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: PFACOKZCDNYPNX-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R)-2-[3,5-bis(prop-2-enoxy)phenyl]-2-hydroxyacetonitrile 在 lithium aluminium tetrahydride 、 硫酸 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 27.0h， 生成 (R)-1-[3,5-bis-(allyloxy)phenyl]-2-(tert-butylamino)ethanol
  参考文献：
  名称：

  Synthesis of the Adrenergic Bronchodilators (R)-Terbutaline and (R)-Salbutamol from (R)-Cyanohydrins¹

  摘要：

  Stereoselective syntheses of (R)-terbutaline and (R)-salbutamol acetal, which are important bronchodilators, starting from O-protected (R)-cyanohydrins are described. (R)-Terbutaline hydrochloride (R)-9.HCl is obtained in an overall yield of 44% with >98% ee from the O-bisallyl-protected cyanohydrin (R)-4k via a Ritter N-tertiary butylation to the amide (R)-6a, hydrogenation to the amino alcohol (R)-7a, and deprotection of the hydroxyl functions. (R)-Salbutamol acetals (R)-7b,c can be obtained from the corresponding O-protected (R)-cyanohydrins either via the route described for (R)-terbutaline or via selective hydrogenation of the protected cyanohydrin (R)-11 to the imino derivative, transimination with tert-butylamine, followed by hydrogenation with NaBH4 to give the 2-amino alcohol derivative (R)-12. Desilylation of(R)-12 to (R)-7c is performed with LiAlH4. Hydrolytic cleavage of the acetals (R)-7b and c to (R)-salbutamol was not yet possible without racemization.

  DOI：

  10.1021/jo970032d
• 作为产物：
  描述：

  allyl 3,5-bis(allyloxy)benzoate 在 lithium aluminium tetrahydride 、 扁桃腈裂解酶来源于杏仁 、 sodium acetate 、 pyridinium chlorochromate 作用下， 以 乙醚 、 二氯甲烷 、 异丙醚 为溶剂， 反应 42.0h， 生成 (2R)-2-[3,5-bis(prop-2-enoxy)phenyl]-2-hydroxyacetonitrile
  参考文献：
  名称：

  Synthesis of the Adrenergic Bronchodilators (R)-Terbutaline and (R)-Salbutamol from (R)-Cyanohydrins¹

  摘要：

  Stereoselective syntheses of (R)-terbutaline and (R)-salbutamol acetal, which are important bronchodilators, starting from O-protected (R)-cyanohydrins are described. (R)-Terbutaline hydrochloride (R)-9.HCl is obtained in an overall yield of 44% with >98% ee from the O-bisallyl-protected cyanohydrin (R)-4k via a Ritter N-tertiary butylation to the amide (R)-6a, hydrogenation to the amino alcohol (R)-7a, and deprotection of the hydroxyl functions. (R)-Salbutamol acetals (R)-7b,c can be obtained from the corresponding O-protected (R)-cyanohydrins either via the route described for (R)-terbutaline or via selective hydrogenation of the protected cyanohydrin (R)-11 to the imino derivative, transimination with tert-butylamine, followed by hydrogenation with NaBH4 to give the 2-amino alcohol derivative (R)-12. Desilylation of(R)-12 to (R)-7c is performed with LiAlH4. Hydrolytic cleavage of the acetals (R)-7b and c to (R)-salbutamol was not yet possible without racemization.

  DOI：

  10.1021/jo970032d

文献信息

• Synthesis of the Adrenergic Bronchodilators (<i>R</i>)-Terbutaline and (<i>R</i>)-Salbutamol from (<i>R</i>)-Cyanohydrins¹
  作者：Franz Effenberger、Jürgen Jäger

  DOI：10.1021/jo970032d

  日期：1997.6.13

  Stereoselective syntheses of (R)-terbutaline and (R)-salbutamol acetal, which are important bronchodilators, starting from O-protected (R)-cyanohydrins are described. (R)-Terbutaline hydrochloride (R)-9.HCl is obtained in an overall yield of 44% with >98% ee from the O-bisallyl-protected cyanohydrin (R)-4k via a Ritter N-tertiary butylation to the amide (R)-6a, hydrogenation to the amino alcohol (R)-7a, and deprotection of the hydroxyl functions. (R)-Salbutamol acetals (R)-7b,c can be obtained from the corresponding O-protected (R)-cyanohydrins either via the route described for (R)-terbutaline or via selective hydrogenation of the protected cyanohydrin (R)-11 to the imino derivative, transimination with tert-butylamine, followed by hydrogenation with NaBH4 to give the 2-amino alcohol derivative (R)-12. Desilylation of(R)-12 to (R)-7c is performed with LiAlH4. Hydrolytic cleavage of the acetals (R)-7b and c to (R)-salbutamol was not yet possible without racemization.