N-(4-methoxyphenyl)-3-benzyl-2,2-difluoropropano-3-lactam | 330801-32-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: N-(4-methoxyphenyl)-3-benzyl-2,2-difluoropropano-3-lactam
• 英文别名: 4-benzyl-3,3-difluoro-1-(4-methoxyphenyl)azetidin-2-one
• CAS: 330801-32-6
• 化学式: C₁₇H₁₅F₂NO₂
• 分子量: 303.308
• InChiKey: ATBSZNQAHWCKCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  N-(4-methoxyphenyl)-3-benzyl-2,2-difluoropropano-3-lactam 在 sodium hydroxide 、 硫酸 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 methyl 2,2-difluoro-3-[N-(4-methoxyphenyl)amino]-4-phenylbutanoate
  参考文献：
  名称：

  Synthesis of (Z)-fluoroalkene dipeptide isosteres utilizing organocopper-mediated reduction of γ,γ-difluoro-α,β-enoates

  摘要：

  gamma,gamma -Difluoro-alpha,beta -enoates are reduced with organocopper reagents to afford the corresponding gamma -fluoro-beta,gamma -enoates. This organocopper-mediated reduction was applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(00)01924-9
• 作为产物：
  描述：

  ethyl 2,2-difluoro-3-hydroxy-4-phenylbutanoate 在 sodium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 4.5h， 生成 N-(4-methoxyphenyl)-3-benzyl-2,2-difluoropropano-3-lactam
  参考文献：
  名称：

  SmI₂-Mediated Reduction of γ,γ-Difluoro-α,β-enoates with Application to the Synthesis of Functionalized (Z)-Fluoroalkene-Type Dipeptide Isosteres

  摘要：

  A samarium diiodide (SmI2)-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI2 proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to a-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI2-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF=CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the a-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.

  DOI：

  10.1021/jo035709d