(4S)-3,3-difluoro-1-((1R)-2-hydroxy-1-phenylethyl)-4-phenylazetidin-2-one | 252681-03-1

• 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: (4S)-3,3-difluoro-1-((1R)-2-hydroxy-1-phenylethyl)-4-phenylazetidin-2-one
• 英文别名: (4S)-3,3-difluoro-1-[(1R)-2-hydroxy-1-phenylethyl]-4-phenylazetidin-2-one
• CAS: 252681-03-1
• 化学式: C₁₇H₁₅F₂NO₂
• 分子量: 303.308
• InChiKey: SSBFUIKAQFHWNJ-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-3,3-difluoro-1-((1R)-2-hydroxy-1-phenylethyl)-4-phenylazetidin-2-one 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 (2-{Benzyl-[(S)-2,2-difluoro-3-((R)-2-hydroxy-1-phenyl-ethylamino)-3-phenyl-propionyl]-amino}-2-phenyl-acetylamino)-acetic acid ethyl ester
  参考文献：
  名称：

  Synthesis of difluorinated pseudopeptides using chiral α,α-difluoro-β-amino acids in the Ugi reaction

  摘要：

  2,2-Difluoro-3-(2-hydroxy-1 R-phenylethylamino)-3 S-phenylpropionic acid 3, obtained by a Reformatsky-type reaction of ethyl bromodifluoroacetate with (4R)-2,4-diphenyloxazolidine, was used as a classical carboxylic acid in the Ugi reaction to prepare various difluorinated pseudopeptides 5a-n. Compounds 5 were then deprotected by hydrogenolysis to furnish difluorinated pseudopeptides 6. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2003.11.019
• 作为产物：
  描述：

  二氟溴乙酸乙酯 、 2,4-diphenyl-1,3-oxazolidine 在 锌 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以65%的产率得到(4S)-3,3-difluoro-1-((1R)-2-hydroxy-1-phenylethyl)-4-phenylazetidin-2-one
  参考文献：
  名称：

  Enantioselective Synthesis of α,α-Difluoro-β-amino Acid and 3,3-Difluoroazetidin-2-one via the Reformatsky-Type Reaction of Ethyl Bromodifluoroacetate with Chiral 1,3-Oxazolidines

  摘要：

  Chiral oxazolidines 2a-e can be diastereoselectively alkylated with BrCF2CO2Et to furnish 3,3-difluoroazetidin-2-ones 3a-e with up to 99% de. Selective cleavage of the chiral appendage provided the corresponding unsubstituted azetidinones. Formation of optically pure a,a-difluoro-P-amino acids 5a-c can be achieved by acidic hydrolysis of N-vinyl-azetidin-2-ones.

  DOI：

  10.1021/jo990868b

文献信息

• Rhodium-catalyzed Reformatsky-type reaction for asymmetric synthesis of difluoro-β-lactams using menthyl group as a chiral auxiliary
  作者：Atsushi Tarui、Daiki Ozaki、Naoko Nakajima、Yuto Yokota、Yasser S. Sokeirik、Kazuyuki Sato、Masaaki Omote、Itsumaro Kumadaki、Akira Ando

  DOI：10.1016/j.tetlet.2008.04.101

  日期：2008.6

  developed a new methodology for the asymmetric Reformatsky-type reaction of (−)-menthyl bromodifluoroacetate (2) with imine in the presence of RhCl(PPh3)3. Ester 2 with the cost-effective chiral auxiliary gave (S)-difluoro-β-lactams in moderate to good yields and high diastereoselectivities through spontaneous removal of the auxiliary.

  我们开发了一种新的方法，用于在RhCl（PPh 3）3存在下（-）-薄荷基溴二氟乙酸酯（2）与亚胺的不对称Reformatsky型反应。带有成本有效的手性助剂的酯2通过自发除去助剂，以中等至良好的收率和较高的非对映选择性获得（S）-二氟-β-内酰胺。
• Chemoselective and stereoselective synthesis of gem-difluoro-β-aminoesters or gem-difluoro-β-lactams from ethylbromodifluoroacetate and imines during Reformatsky reaction
  作者：Nicolas Boyer、Philippe Gloanec、Guillaume De Nanteuil、Philippe Jubault、Jean-Charles Quirion

  DOI：10.1016/j.tet.2007.09.058

  日期：2007.12

  The chemoselective and stereoselective synthesis of gem-difluoro-beta-amiinoesters or genz-difluoro-beta-lactams was investigated from ethylbromodifluoroacetate and imines during Reformatsky reaction. Influence of various reaction parameters, such as nature of the amine part, nature of the chiral auxiliary, was evaluated. High levels of stereoselectivity (up to 98%) were obtained for gem-difluoro-beta-aminoesters and gem-difluoro-beta-lactams using either (R)-phenylglycinol or (R)-methoxyphenylglycinol. (c) 2007 Elsevier Ltd. All rights reserved.
• The Diastereoselective Synthesis of Difluoro-b-lactam Using Reformatsky-Honda Reaction
  作者：Atsushi Tarui、Keigo Kondo、Hiroko Taira、Kazuyuki Sato、Masaaki Omote、Itsumaro Kumadaki、Akira Ando

  DOI：10.3987/com-07-s(u)29

  日期：——

  The high diastereoselective synthesis of chiral difluoro-beta-lactams (3) was attained by treatment of ethyl bromodifluoroacetate (1), 2-hydroxy-1-phenylethyl group substituted imines (2) and diethylzinc in the presence of rhodium-catalyst. The absolute configuration of 3 was determined by X-ray analysis of 3,5-dinitrobenzoate (6) derived from 3.
• Enantioselective Synthesis of α,α-Difluoro-β-amino Acid and 3,3-Difluoroazetidin-2-one via the Reformatsky-Type Reaction of Ethyl Bromodifluoroacetate with Chiral 1,3-Oxazolidines
  作者：Stéphane Marcotte、Xavier Pannecoucke、Christian Feasson、Jean-Charles Quirion

  DOI：10.1021/jo990868b

  日期：1999.11.1

  Chiral oxazolidines 2a-e can be diastereoselectively alkylated with BrCF2CO2Et to furnish 3,3-difluoroazetidin-2-ones 3a-e with up to 99% de. Selective cleavage of the chiral appendage provided the corresponding unsubstituted azetidinones. Formation of optically pure a,a-difluoro-P-amino acids 5a-c can be achieved by acidic hydrolysis of N-vinyl-azetidin-2-ones.
• Synthesis of difluorinated pseudopeptides using chiral α,α-difluoro-β-amino acids in the Ugi reaction
  作者：Vanessa Gouge、Philippe Jubault、Jean-Charles Quirion

  DOI：10.1016/j.tetlet.2003.11.019

  日期：2004.1

  2,2-Difluoro-3-(2-hydroxy-1 R-phenylethylamino)-3 S-phenylpropionic acid 3, obtained by a Reformatsky-type reaction of ethyl bromodifluoroacetate with (4R)-2,4-diphenyloxazolidine, was used as a classical carboxylic acid in the Ugi reaction to prepare various difluorinated pseudopeptides 5a-n. Compounds 5 were then deprotected by hydrogenolysis to furnish difluorinated pseudopeptides 6. (C) 2003 Elsevier Ltd. All rights reserved.