(R)-1-benzyl-3-hydroxy-4,4-dimethylpyrrolidin-2-one | 1227380-63-3

• 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: (R)-1-benzyl-3-hydroxy-4,4-dimethylpyrrolidin-2-one
• 英文别名: (R)-N-benzylpantolactam；N-benzyl-(R)-pantolactam；(3R)-1-benzyl-3-hydroxy-4,4-dimethylpyrrolidin-2-one
• CAS: 1227380-63-3
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: QGIAXCPKXOERCB-NSHDSACASA-N

物化性质

• 沸点：
  396.3±42.0 °C(Predicted)
• 密度：
  1.154±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-1-benzyl-3-hydroxy-4,4-dimethylpyrrolidin-2-one 、 4-氟-2-(三氟甲基)苯甲腈 在 potassium phosphate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以72%的产率得到(R)-4-(1-benzyl-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)-2-(trifluoromethyl)-benzonitrile
  参考文献：
  名称：

  Rational Design of a Topical Androgen Receptor Antagonist for the Suppression of Sebum Production with Properties Suitable for Follicular Delivery

  摘要：

  A novel nonsteroidal androgen receptor antagonist, (R)-4-(1-benzy1-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)2-(trifluoromethyl)benzonitrile (1), for the topical control of sebum production is reported. This compound, which is potent, selective, and efficacious in the clinically validated golden Syrian hamster ear animal model, was designed to be delivered to the pilosebaceous unit, the site of action, preferentially by the follicular route.

  DOI：

  10.1021/jm9018004
• 作为产物：
  描述：

  D-(-)-泛酰内酯 在 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 27.5h， 生成 (R)-1-benzyl-3-hydroxy-4,4-dimethylpyrrolidin-2-one
  参考文献：
  名称：

  酰基氯与 (R)-泛内酯衍生物原位生成的酮的高度非对映选择性酯化

  摘要：

  我们的机理研究表明，Et3N 是通过乙烯酮衍生的复合物从相应的酰氯与 (R)-泛内酯形成高度非对映选择性形成酯的关键要求。此外，我们发现 (R)-N-苄基-泛内酰胺是比 (R)-泛内酯更有效的手性醇，用于原位生成的烯酮的酯化。

  DOI：

  10.1002/ejoc.201301383

文献信息

• An efficient synthesis of highly functionalized chiral lactams
  作者：Martha A. Ornelas、Javier Gonzalez、Neal W. Sach、Paul F. Richardson、Kevin D. Bunker、Angelica Linton、Susan E. Kephart、Mason Pairish、Chuangxing Guo

  DOI：10.1016/j.tetlet.2011.07.021

  日期：2011.9

  A new method was developed to synthesize highly functionalized lactams via a one pot reductive amination/lactam formation reaction. This methodology is amenable for parallel synthesis and was used to prepare a large number of lactam analogs in a library format with good ee (de) retention. (C) 2011 Elsevier Ltd. All rights reserved.
• Highly Diastereoselective Esterification of Ketenes Generated In Situ from Acyl Chlorides with (<i>R</i>)-Pantolactone Derivatives
  作者：Takafumi Yamagami、Masanori Hatsuda、Masayuki Utsugi、Ryo Kobayashi、Yasunori Moritani

  DOI：10.1002/ejoc.201301383

  日期：2013.11

  revealed that Et3N is a key requirement for the highly diastereoselective formation of esters from the corresponding acyl chlorides with (R)-pantolactone via ketene-derived complexes. Furthermore, we have discovered that (R)-N-benzyl-pantolactam is a more effective chiral alcohol than (R)-pantolactone for the esterification of in situ generated ketenes.

  我们的机理研究表明，Et3N 是通过乙烯酮衍生的复合物从相应的酰氯与 (R)-泛内酯形成高度非对映选择性形成酯的关键要求。此外，我们发现 (R)-N-苄基-泛内酰胺是比 (R)-泛内酯更有效的手性醇，用于原位生成的烯酮的酯化。
• Rational Design of a Topical Androgen Receptor Antagonist for the Suppression of Sebum Production with Properties Suitable for Follicular Delivery
  作者：Lorna H. Mitchell、Theodore R. Johnson、Guang Wei Lu、Daniel Du、Kaushik Datta、Felicity Grzemski、Veerabahu Shanmugasundaram、Julie Spence、Kim Wade、Zhi Wang、Kevin Sun、Kristin Lin、Lain-Yen Hu、Karen Sexton、Neil Raheja、Catherine Kostlan、David Pocalyko

  DOI：10.1021/jm9018004

  日期：2010.6.10

  A novel nonsteroidal androgen receptor antagonist, (R)-4-(1-benzy1-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)2-(trifluoromethyl)benzonitrile (1), for the topical control of sebum production is reported. This compound, which is potent, selective, and efficacious in the clinically validated golden Syrian hamster ear animal model, was designed to be delivered to the pilosebaceous unit, the site of action, preferentially by the follicular route.