trans-1-(N,N-diethylamino)-4-phenylazetidin-2-one | 113830-78-7

• 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: trans-1-(N,N-diethylamino)-4-phenylazetidin-2-one
• 英文别名: trans-1-methyl-3-(N,N-diethylamino)-4-phenyl-2-azetidinone；trans-1-Methyl-3-diethylamino-4-phenyl-2-azetidinone；(3S,4S)-3-(diethylamino)-1-methyl-4-phenylazetidin-2-one
• CAS: 113830-78-7
• 化学式: C₁₄H₂₀N₂O
• 分子量: 232.326
• InChiKey: KXXGDFDCNAYKFX-STQMWFEESA-N

物化性质

• 沸点：
  375.2±42.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-二乙基氨基乙酸乙酯 、 苯亚甲基甲胺 生成 trans-1-(N,N-diethylamino)-4-phenylazetidin-2-one
  参考文献：
  名称：

  由烯醇锌和亚胺选择性形成1,3,4-三取代和3,4-二取代的反式-β-内酰胺

  摘要：

  据报导一种高产率合成（最好是90％以上）的反式-β-内酰胺类化合物（azetidin-2-ones）的新方法，该方法涉及α-氨基酸酯烯醇锌与适当的亚胺的1：1反应。该反应可以作为“一锅法”合成进行，正如合成反式-3-二乙基氨基-4-苯基氮杂环丁烷-2-酮所证明的那样（93％收率）。由于分子内螯合物的配位，新型的烯醇锌很可能具有Z-几何形状。已经获得的证据是，在第一步中，这些烯醇锌以高度非对映选择性的方式与亚胺反应，提供苏式醛缩醛酸酯，在随后的步骤中将其闭环成氮杂环丁烷-2-酮。

  DOI：

  10.1002/recl.19871060910

文献信息

• Meta-containing enolate compounds
  申请人：Gist-Brocades N.V.

  公开号：US04898955A1

  公开（公告）日：1990-02-06

  Trans-.beta.-lactams are prepared in a nearly quantitative yield by a condensation reaction of a new intermediate metal enolate and an appropriate imine. Certain new metal enolates are provided as intermediates.

  通过一种新的中间体金属烯醇酸盐和适当的亚胺的缩合反应，制备出几乎定量收率的转β-内酰胺。同时提供了某些新的金属烯醇酸盐作为中间体。
• A new and efficient route to 3-amino-2-azetidinones via zinc enolates of N,N-disubstituted glycine esters
  作者：Fred H. Van der Steen、Henk Kleijn、Johann T. B. H. Jastrzebski、Gerard Van Koten

  DOI：10.1021/jo00017a030

  日期：1991.8

  This report describes novel and efficient ''one-pot'' syntheses of 1-unsubstituted-3-amino-4-substituted-2-azetidinones (8 and 9) involving the in situ preparation of lithium and particularly zinc enolates (5 and 6, respectively) of N,N-disubstituted glycine esters (4) and subsequent reactions of these enolates with (simple) imines (7). Lithium enolates 5 only react with activated imines that are N-substituted with an electron-withdrawing group (e.g. aryl, trialkylsilyl), affording cis-3-amino-2-azetidinones in excellent yields with moderate to good stereoselectivity (de 68-92%). Zinc enolates 6 are more generally applicable since they react with activated imines as well as unactivated imines (e.g. those which are N-substituted with an electron-donating group such as alkyl) to afford 3-amino-2-azetidinones in excellent yields. The trans diastereoselectivity of the zinc-mediated enolate-imine condensation can be tuned by changing the steric and electronic properties of the substituents of the reagents (i.e. both enolate and imine), as well as the solvent polarity. The observed stereoselectivities are explained in terms of two highly ordered transition states, consisting of a Z-zinc ester enolate and an E-imine. Protection of the amino function of the metal enolates as a 2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane ring affords 2-azetidinone products that can be easily deprotected to provide a free 3-amino function. In this way, trans-1-benzyl-3-(protected amino)-4-methyl-2-azetidinone (9a) and trans-3-(protected amino)-4-[(trimethylsilyl)ethynyl]-2-azetidinone (9g), key intermediates in the synthesis of Aztreonam (and 9g for bicyclic beta-lactam antibiotics as well), have been prepared in excellent yields (98 and 93%, respectively) with a high diastereoselectivity (de 82 and 94%, respectively). Furthermore, depending on the reactivity of imines 7, our method is also applicable using a catalytic amount (10 mol %) of ZnCl2.
• A synthesis for beta-lactams with the aid of a metal compound
  申请人：RIJKSUNIVERSITEIT UTRECHT

  公开号：EP0281177B1

  公开（公告）日：1993-09-01
• Enantioselective synthesis of 3-amino-2-azetidinones via the ester enolate - imine condensation
  作者：Fred H. Van der Steen、Henk Kleijn、George J. P. Britovsek、Johann T. B. H. Jastrzebski、Gerard Van Koten

  DOI：10.1021/jo00040a034

  日期：1992.7

  Three approaches to the enantioselective synthesis of 3-amino-4-substituted-2-azetidinones by condensation of alpha-amino ester enolates with imines are described: (i) application of chiral ester derivatives of NN-diethylglycine; (ii) application of chiral N-(alpha-methylbenzyl)imines; and (iii) application of chiral imines derived from (2R)-2,3-O-isopropylideneglyceraldehyde. Zinc and aluminum enolates of (-)-menthyl- and (-)-bornyl NN-diethylglycine esters react with simple imines to selectively afford trans-3-(diethylamino)-2-azetidinones, but with a low chiral induction (ee 0-35%). However, reactions of the metal (Li, Zn, Al) ester enolates of (2,2,5,5-tetramethyl-1-aza-2,4-disilacyclopent-1-yl)acetic acid ethyl ester (1c) with N-(alpha-methylbenzyl)imines yield N-protected 3-amino-2-azetidinones in excellent yields and with very high diastereo- and enantioselectivities. The best results are obtained for the zinc-mediated reactions. For example, trans-(3R,4S)-1(R)-(alpha-methylbenzyl)-3-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)-4-[N-(R)-(alpha-methylbenzyl)imino]-2-azeti dineone (4a), a fully protected key intermediate (having the unnatural C-3 configuration) for the synthesis of known monobactam and bicyclic beta-lactam antibiotics, was synthesized in 91% yield with an ee of 91%. Application of chiral imines derived from acetaldehyde and propionaldehyde enable, depending on the solvent, the selective high yielding synthesis (de 60-99%; ee >95%) of any one of the four stereoisomers of 3-amino-4-alkyl-2-azetidinones, which are key intermediates for the synthesis of Aztreonam and related antibiotics. In Et2O, a weakly polar solvent, the trans isomers are formed, whereas the use of a polar THF/HMPA solvent mixture results in formation of the cis isomers. Reaction of the zinc enolate of 1c with the N-(4-methoxyphenyl)imine derivative 2i of (2R)-2,3-O-isopropylidene glyceraldehyde affords trans-(3R,4S)-3-amino-4-[(1'S)-1',2'-O-isopropylideneethyl]-2-azetidinone (10a) in excellent yield (de 86%; ee >98%), whereas reaction of the lithium enolate of 1c with the N-(trimethylsilyl)imine derivative 21 affords the cis-(3S,4S) isomer 10d (key intermediate for the synthesis of Carumonam) in good yield (de >90%; >90%). A rationale for the observed stereoselectivities in terms of highly ordered transition states is presented.
• US4898955A
  申请人：——

  公开号：US4898955A

  公开（公告）日：1990-02-06