3-isoxazolecarboxylic acid 5-[(2,2-hydroxyphenyl)ethyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester | 386707-48-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-isoxazolecarboxylic acid 5-[(2,2-hydroxyphenyl)ethyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester
• 英文别名: 5-(2-phenyl-2-hydroxy-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester；ethyl 5-[2-hydroxy-2-phenyl-ethyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)isoxazole-3-carboxylate；Ethyl 5-(2-hydroxy-2-phenylethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-1,2-oxazole-3-carboxylate
• CAS: 386707-48-8
• 化学式: C₂₁H₂₇NO₆
• 分子量: 389.448
• InChiKey: KJPNJAVSDUHPLC-UHFFFAOYSA-N

物化性质

• 沸点：
  522.6±50.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  91
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-isoxazolecarboxylic acid 5-[(2,2-hydroxyphenyl)ethyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 以96%的产率得到5-(2-phenyl-2-keto-ethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-3-isoxazolecarboxylic acid ethyl ester
  参考文献：
  名称：

  酮异恶唑聚酮化合物的制备

  摘要：

  在异恶唑环和其他含氮官能团的存在下，醇的戴斯-马丁高碘烷 (DMP) 氧化以良好的产率进行。DMP 路线允许制备高度支化的聚酮化合物合成等价物。

  DOI：

  10.1055/s-2003-42052
• 作为产物：
  描述：

  4-乙酰基-5-甲基异恶唑-3-甲酸乙酯 在 正丁基锂 、 对甲苯磺酸 、 二异丙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 正己烷 、 苯 为溶剂， 反应 12.17h， 生成 3-isoxazolecarboxylic acid 5-[(2,2-hydroxyphenyl)ethyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester
  参考文献：
  名称：

  An improved procedure for the lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate

  摘要：

  Ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate was smoothly lithiated at the 5-methyl position, when the 4-acetyl group was protected with a 5,5-dimethyl-1,3-dioxanyl group. The lithio anion was quenched with a variety of electrophiles such as alkyl halides, aldehydes, TMSCl, and Me3SnCl in good to excellent yields. The lithiation of the unprotected compound and the 4-acetyl group protected as 1,3-dioxolanyl both failed. The effects of different bases have been investigated and the addition of LiCl significantly increased yields. Based on variable temperature NMR studies the 5,5-dimethyl-1,3-dioxanyl group appears to occupy a single chair conformation which may facilitate lateral metalation. This represents a facile entry into 5-functionalized 3-isoxazolyl carboxylic acid derivatives as prodrugs for the AMPA glutamate neurotransmitters of the central nervous system. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(01)00781-5

文献信息

• Preparation of Keto-Isoxazole Polyketide Synthons
  作者：Nicholas R. Natale、Jared K. Nelson、David J. Burkhart、Andrew McKenzie

  DOI：10.1055/s-2003-42052

  日期：——

  of alcohols, proceeds in good to excellent yield in the presence of the isoxazole ring, and other nitrogen-containing functional groups. The DMP route allows for the preparationof highly branched polyketide synthetic equivalents.

  在异恶唑环和其他含氮官能团的存在下，醇的戴斯-马丁高碘烷 (DMP) 氧化以良好的产率进行。DMP 路线允许制备高度支化的聚酮化合物合成等价物。
• Catalytic Asymmetric Synthesis of Glutamate Analogues
  作者：David J. Burkhart、Andrew R. McKenzie、Jared K. Nelson、Katherine I. Myers、Xue Zhao、Kathy R. Magnusson、Nicholas R. Natale

  DOI：10.1021/ol049619m

  日期：2004.4.1

  Utilizing our lateral metalation coupled with Jacobsen's catalytic asymmetric amino nitrile synthesis, we have demonstrated the ability to synthesize isoxazole-containing amino acid glutamate analogues in high yield and high enantiomeric excesses. Chiral centers alpha or beta at the C-5 position do not detract from diastereoselectivity of the Jacobsen-Strecker reaction.
• An improved procedure for the lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate
  作者：David J Burkhart、Peiwen Zhou、Alex Blumenfeld、Brendan Twamley、Nicholas R Natale

  DOI：10.1016/s0040-4020(01)00781-5

  日期：2001.9

  Ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate was smoothly lithiated at the 5-methyl position, when the 4-acetyl group was protected with a 5,5-dimethyl-1,3-dioxanyl group. The lithio anion was quenched with a variety of electrophiles such as alkyl halides, aldehydes, TMSCl, and Me3SnCl in good to excellent yields. The lithiation of the unprotected compound and the 4-acetyl group protected as 1,3-dioxolanyl both failed. The effects of different bases have been investigated and the addition of LiCl significantly increased yields. Based on variable temperature NMR studies the 5,5-dimethyl-1,3-dioxanyl group appears to occupy a single chair conformation which may facilitate lateral metalation. This represents a facile entry into 5-functionalized 3-isoxazolyl carboxylic acid derivatives as prodrugs for the AMPA glutamate neurotransmitters of the central nervous system. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Preparation of chiral isoxazole carbinols via catalytic asymmetric Corey-Bakshi-Shibata reduction.
  作者：Nicholas R. Natale、Kevin C. Rider、David J. Burkhart、Chun Li、Andrew R. McKenzie、Jared K. Nelson

  DOI：10.3998/ark.5550190.0011.809

  日期：——

  A diverse set of isoxazoles, with activity in three different disease categories, was reduced asymmetrically from pro-chiral ketones to chiral alcohols using the Corey-Bakshi-Shibata methodology at the α, β, and γ positions relative to the C-5-methyl of the isoxazole. The experiments described provide an easy route to hydroxylated isoxazoles that represent the common CYP-450 3A4 metabolic site.

  使用 Corey-Bakshi-Shibata 方法在相对于 C-5-甲基的 α、β 和 γ 位置，一组不同的异恶唑在三种不同的疾病类别中具有活性，从前手性酮不对称地减少到手性醇异恶唑。所描述的实验为羟基化异恶唑提供了一种简单的途径，代表常见的 CYP-450 3A4 代谢位点。