(4R,5R)-4-(3-cyclopentyloxy-4-methoxyphenyl)-5-hydroxypyrrolidin-2-one | 145548-99-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (4R,5R)-4-(3-cyclopentyloxy-4-methoxyphenyl)-5-hydroxypyrrolidin-2-one
• CAS: 145548-99-8
• 化学式: C₁₆H₂₁NO₄
• 分子量: 291.347
• InChiKey: BBKLSQQEZLEDLF-MLGOLLRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R,5R)-4-(3-cyclopentyloxy-4-methoxyphenyl)-5-hydroxypyrrolidin-2-one 在 盐酸 、 溴甲酚绿 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以73%的产率得到(R)-(-)-咯利普兰
  参考文献：
  名称：

  The synthesis of aracemic 4-substituted pyrrolidinones and 3-substituted pyrrolidines. An asymmetric synthesis of (-)-rolipram

  摘要：

  Conjugate additions of RCuCNLi to the chiral alpha,beta-unsaturated lactam 4 gives almost exclusive exo addition-a reversal in stereochemistry when cuprates were added to chiral lactam 1. The lactams 5 were transformed into 4-substituted pyrrolidinones 8 via a three-step sequence which involved decarbalkoxylation, silane reduction and metal-ammonia benzylamine cleavage. The chemical yields as well as the enantiomeric purity were very high for this process. As an example of the usefulness of this scheme, the antidepressant (-)-Rolipram was prepared in good overall yield. Furthermore, the bicyclic lactams 6 were readily transformed, using alane as the reducing agent, to 3-substituted pyrrolidines 11. Absolute configurations of 8 and 11 were confirmed by comparison with literature assignments which also gave strong support to the facial addition of the cuprates to 4.

  DOI：

  10.1021/jo00053a012
• 作为产物：
  描述：

  4-溴-2-(环戊基氧基)苯甲醚 在 palladium on activated charcoal 氨 、 ammonium formate 、 calcium 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 (4R,5R)-4-(3-cyclopentyloxy-4-methoxyphenyl)-5-hydroxypyrrolidin-2-one
  参考文献：
  名称：

  The synthesis of aracemic 4-substituted pyrrolidinones and 3-substituted pyrrolidines. An asymmetric synthesis of (-)-rolipram

  摘要：

  Conjugate additions of RCuCNLi to the chiral alpha,beta-unsaturated lactam 4 gives almost exclusive exo addition-a reversal in stereochemistry when cuprates were added to chiral lactam 1. The lactams 5 were transformed into 4-substituted pyrrolidinones 8 via a three-step sequence which involved decarbalkoxylation, silane reduction and metal-ammonia benzylamine cleavage. The chemical yields as well as the enantiomeric purity were very high for this process. As an example of the usefulness of this scheme, the antidepressant (-)-Rolipram was prepared in good overall yield. Furthermore, the bicyclic lactams 6 were readily transformed, using alane as the reducing agent, to 3-substituted pyrrolidines 11. Absolute configurations of 8 and 11 were confirmed by comparison with literature assignments which also gave strong support to the facial addition of the cuprates to 4.

  DOI：

  10.1021/jo00053a012