ethyl 4-benzyloxy-2,2-difluoro-3-hydroxybutanoate | 263898-36-8

• 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: ethyl 4-benzyloxy-2,2-difluoro-3-hydroxybutanoate
• 英文别名: ethyl 2,2-difluoro-3-hydroxy-4-phenylmethoxybutanoate
• CAS: 263898-36-8；209851-85-4
• 化学式: C₁₃H₁₆F₂O₄
• 分子量: 274.264
• InChiKey: JADDQCNNHLVNLZ-UHFFFAOYSA-N

物化性质

• 沸点：
  390.3±42.0 °C(Predicted)
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-benzyloxy-2,2-difluoro-3-hydroxybutanoate 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 3.0h， 生成 N-(4-methoxyphenyl)-3-benzyloxymethyl-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
• 作为产物：
  描述：

  二氟溴乙酸乙酯 、 苄氧基乙醛 在 三氟化硼乙醚 、 copper(l) chloride 、 锌 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 以77%的产率得到ethyl 4-benzyloxy-2,2-difluoro-3-hydroxybutanoate
  参考文献：
  名称：

  外消旋 4-Deoxy-4,4-difluoro- 和 2,4-Dideoxy-2,4,4-trifluorohexosides 的从头合成

  摘要：

  一系列外消旋 4-deoxy-4,4-difluorinated 碳水化合物是通过使用面向多样性的 de novo 合成制备的，该合成从三个市售的双碳结构单元开始。通过七个步骤以 35% 的收率制备了一种常见的二氟二氟糖苷，其中使用完善的官能团获得了五种不同的 4-脱氧-4,4-二氟-和 4-脱氧-2,4,4-三氟己基吡喃糖苷操纵。

  DOI：

  10.1002/ejoc.201100565

文献信息

• Preparation of optically active α,α-difluoro-β-hydroxyketones
  作者：Katsuhiko Iseki、Daisuke Asada、Yoshichika Kuroki

  DOI：10.1016/s0022-1139(99)00033-0

  日期：1999.7

  The stereoselective synthesis of α,α-difluoro-β-hydroxyketones of high enantiomeric purity is described starting from optically active α,α-difluoro-β-hydroxy esters. The esters were converted to the corresponding N-methoxy-N-methyl amides, which were treated with Grignard and organolithium reagents to provide the α,α-difluoro-β-hydroxyketones with up to 100% ee.

  从光学活性的α，α-二氟-β-羟基酯开始描述了高对映体纯度的α，α-二氟-β-羟基酮的立体选择性合成。将酯转化为相应的N-甲氧基-N-甲基酰胺，将其用格利雅（Grignard）和有机锂试剂处理，以提供具有高达100％ee的α，α-二氟-β-羟基酮。
• Asymmetric aldol addition of aldehydes to a difluoroketene silyl acetal catalyzed by chiral Lewis acids
  作者：Katsuhiko Iseki、Yoshichika Kuroki、Daisuke Asada、Mie Takahashi、Satoshi Kishimoto、Yoshiro Kobayashi

  DOI：10.1016/s0040-4020(97)00683-2

  日期：1997.7

  substoichiometric amount of chiral Lewis acid 2 or 3 provides the corresponding α,α-difluoro β-hydroxy esters 4–12 with high enantioselectivities (up to 98% ee). Reaction temperature has a great influence on the enantiofacial selection of aldehydes; the reactions of benzyloxyacetaldehyde catalyzed by Lewis acid 2 at −78 and −30°C gave the (+)- and (−)-α,α-difluoro β-hydroxy esters 7 in optical yields of 98% and

  在亚化学计量的手性路易斯酸2或3的存在下，醛与二氟乙烯乙基三甲基甲硅烷基乙缩醛的醛醇缩合反应（1）提供相应的具有高对映选择性（高达98％ee的α，α-二氟β-羟基酯4-12））。反应温度对醛的对面选择有很大的影响。路易斯酸2在-78和-30℃下催化苄氧基乙醛的反应，分别得到（+）-和（-）-α，α-二氟β-羟基酯7，其光学收率分别为98％和85％。
• Gold(I)-Catalyzed Alkoxyhalogenation of β-Hydroxy-α,α-Difluoroynones
  作者：Marie Schuler、Franck Silva、Carla Bobbio、Arnaud Tessier、Véronique Gouverneur

  DOI：10.1002/anie.200802162

  日期：2008.9.29
• SmI₂-Mediated Reduction of γ,γ-Difluoro-α,β-enoates with Application to the Synthesis of Functionalized (<i>Z</i>)-Fluoroalkene-Type Dipeptide Isosteres
  作者：Akira Otaka、Junko Watanabe、Akira Yukimasa、Yoshikazu Sasaki、Hideaki Watanabe、Takayoshi Kinoshita、Shinya Oishi、Hirokazu Tamamura、Nobutaka Fujii

  DOI：10.1021/jo035709d

  日期：2004.3.1

  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.
• De Novo Synthesis of Racemic 4-Deoxy-4,4-difluoro- and 2,4-Dideoxy-2,4,4-trifluorohexosides
  作者：Guy T. Giuffredi、Bruno Bernet、Véronique Gouverneur

  DOI：10.1002/ejoc.201100565

  日期：2011.7

  A range of racemic 4-deoxy-4,4-difluorinated carbohydrates were prepared by using a diversity-oriented de novo synthesis starting with three commercially available two-carbon building blocks. A common gem-difluorinated glycal was prepared in 35 % yield in seven steps, from which five different 4-deoxy-4,4-difluoro- and 4-deoxy-2,4,4-trifluorohexopyranosides were accessed using well-established functional

  一系列外消旋 4-deoxy-4,4-difluorinated 碳水化合物是通过使用面向多样性的 de novo 合成制备的，该合成从三个市售的双碳结构单元开始。通过七个步骤以 35% 的收率制备了一种常见的二氟二氟糖苷，其中使用完善的官能团获得了五种不同的 4-脱氧-4,4-二氟-和 4-脱氧-2,4,4-三氟己基吡喃糖苷操纵。