Ethyl 3,3-difluoro-2-oxo-4-phenylbutanoate | 144156-84-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Ethyl 3,3-difluoro-2-oxo-4-phenylbutanoate
• CAS: 144156-84-3
• 化学式: C₁₂H₁₂F₂O₃
• 分子量: 242.222
• InChiKey: KXACTQRDRCBVSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 3,3-difluoro-2-oxo-4-phenylbutanoate 在 碳酸氢钠 作用下， 以 水 、 异丙醇 为溶剂， 反应 48.0h， 以95%的产率得到3,3-Difluoro-2-oxo-4-phenylbutanoic acid
  参考文献：
  名称：

  .delta.,.epsilon.-Unsaturated .beta.,.beta.-Difluoro-.alpha.-keto Esters: Novel Synthesis and Utility as Precursors of .beta.,.beta.-Difluoro-.alpha.-amino Acids

  摘要：

  Treatment of the hemiketals 6 formed from ethyl trifluoropyruvate and primary allylic alcohols with SOCl2 and pyridine readily afforded a number of alpha-chloro-beta,beta,beta-trifluorolactyl allyl ethers 2. Subsequent reductive dechlorofluorination from 2 led to the formation of allyl-substituted difluoroenol pyruvyl ethers 3 whose Claisen rearrangement provided a convenient access to a variety of delta,epsilon-unsaturated beta,beta-difluoro-alpha-keto esters 4. As further transformation, direct conversion of beta,beta-difluoro-alpha-keto esters to the corresponding beta,beta-difluoro-alpha-amino acids was achieved by reductive amination of the corresponding alpha-keto acids with NH3 . H2O/NaBH4. Furthermore, use of the prepared beta beta-difluoro-alpha-keto ester 4a as a common precursor of other structurally related beta,beta-difluoro-alpha-amino acids was demonstrated by the synthesis of beta,beta-difluoroproline (18) and beta,beta-difluoroglutamic acid (23) through synthetic elaboration of its inherent double bond.

  DOI：

  10.1021/jo00125a013
• 作为产物：
  描述：

  3,3,3-三氟丙酮酸乙酯 在 copper(l) iodide 、 氯化亚砜 、 锌 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 、 xylene 、 苯 为溶剂， 反应 73.0h， 生成 Ethyl 3,3-difluoro-2-oxo-4-phenylbutanoate
  参考文献：
  名称：

  .delta.,.epsilon.-Unsaturated .beta.,.beta.-Difluoro-.alpha.-keto Esters: Novel Synthesis and Utility as Precursors of .beta.,.beta.-Difluoro-.alpha.-amino Acids

  摘要：

  Treatment of the hemiketals 6 formed from ethyl trifluoropyruvate and primary allylic alcohols with SOCl2 and pyridine readily afforded a number of alpha-chloro-beta,beta,beta-trifluorolactyl allyl ethers 2. Subsequent reductive dechlorofluorination from 2 led to the formation of allyl-substituted difluoroenol pyruvyl ethers 3 whose Claisen rearrangement provided a convenient access to a variety of delta,epsilon-unsaturated beta,beta-difluoro-alpha-keto esters 4. As further transformation, direct conversion of beta,beta-difluoro-alpha-keto esters to the corresponding beta,beta-difluoro-alpha-amino acids was achieved by reductive amination of the corresponding alpha-keto acids with NH3 . H2O/NaBH4. Furthermore, use of the prepared beta beta-difluoro-alpha-keto ester 4a as a common precursor of other structurally related beta,beta-difluoro-alpha-amino acids was demonstrated by the synthesis of beta,beta-difluoroproline (18) and beta,beta-difluoroglutamic acid (23) through synthetic elaboration of its inherent double bond.

  DOI：

  10.1021/jo00125a013

文献信息

• Conversion of .alpha.-Keto Esters into .beta.,.beta.-Difluoro-.alpha.-keto Esters and Corresponding Acids: A Simple Route to a Novel Class of Serine Protease Inhibitors
  作者：Melchiorre F. Parisi、Giuseppe Gattuso、Anna Notti、Francisco M. Raymo、Robert H. Abeles

  DOI：10.1021/jo00121a040

  日期：1995.8

  The preparation of a series of beta,beta-difluoro-alpha-keto esters and corresponding acids RCF(2)COCO(2)R' (R = Me, Et; i-Pr, Bn, and Ph; R' = Et and H), designed as potential inhibitors of serine proteases, is described. The standard procedure developed consists in the initial formation of an alpha,alpha-difluoro ester from an alpha-keto ester, followed by a simple four-step sequence involving the synthesis of hemiacetal, cyanohydrin, and alpha-hydroxy ester difluorinated intermediates. This method provides an easy route to beta,beta-difluoro-alpha-keto esters and corresponding acids, via ''formal'' insertion of a difluoromethylene group between the R substituent and the alpha-carbonyl group of a generic alpha-keto ester.
• .delta.,.epsilon.-Unsaturated .beta.,.beta.-Difluoro-.alpha.-keto Esters: Novel Synthesis and Utility as Precursors of .beta.,.beta.-Difluoro-.alpha.-amino Acids
  作者：Guo-qiang Shi、Wei-ling Cai

  DOI：10.1021/jo00125a013

  日期：1995.10

  Treatment of the hemiketals 6 formed from ethyl trifluoropyruvate and primary allylic alcohols with SOCl2 and pyridine readily afforded a number of alpha-chloro-beta,beta,beta-trifluorolactyl allyl ethers 2. Subsequent reductive dechlorofluorination from 2 led to the formation of allyl-substituted difluoroenol pyruvyl ethers 3 whose Claisen rearrangement provided a convenient access to a variety of delta,epsilon-unsaturated beta,beta-difluoro-alpha-keto esters 4. As further transformation, direct conversion of beta,beta-difluoro-alpha-keto esters to the corresponding beta,beta-difluoro-alpha-amino acids was achieved by reductive amination of the corresponding alpha-keto acids with NH3 . H2O/NaBH4. Furthermore, use of the prepared beta beta-difluoro-alpha-keto ester 4a as a common precursor of other structurally related beta,beta-difluoro-alpha-amino acids was demonstrated by the synthesis of beta,beta-difluoroproline (18) and beta,beta-difluoroglutamic acid (23) through synthetic elaboration of its inherent double bond.