3-isoxazolecarboxylic acid 5-[(methylthio)methyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester

• 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-[(methylthio)methyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester
• 英文别名: Ethyl 5-(methylsulfanylmethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-1,2-oxazole-3-carboxylate；ethyl 5-(methylsulfanylmethyl)-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-1,2-oxazole-3-carboxylate
• 化学式: C₁₅H₂₃NO₅S
• 分子量: 329.417
• InChiKey: UGCLTHOOSCSTJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  96.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-乙酰基-5-甲基异恶唑-3-甲酸乙酯 在 对甲苯磺酸 、 lithium diisopropyl amide 作用下， 以 苯 为溶剂， 生成 3-isoxazolecarboxylic acid 5-[(methylthio)methyl]-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester
  参考文献：
  名称：

  Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate with 5,5-dimethyl-1,3-dioxanyl as a directing group

  摘要：

  Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate, a functionalized isoxazole AMPA analog, occurs cleanly at the C-5 methyl group with 5,5-dimethyl-1,3-dioxanyl as a directing group. The 4-acetyl isoxazole derivatives were transformed selectively by a modified Willgerodt-Kindler reaction into the corresponding homologated methyl esters after deprotection. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01782-1

文献信息

• Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate with 5,5-dimethyl-1,3-dioxanyl as a directing group
  作者：Peiwen Zhou、N.R. Natale

  DOI：10.1016/s0040-4039(98)01782-1

  日期：1998.11

  Lateral lithiation of ethyl 4-acetyl-5-methyl-3-isoxazolyl carboxylate, a functionalized isoxazole AMPA analog, occurs cleanly at the C-5 methyl group with 5,5-dimethyl-1,3-dioxanyl as a directing group. The 4-acetyl isoxazole derivatives were transformed selectively by a modified Willgerodt-Kindler reaction into the corresponding homologated methyl esters after deprotection. (C) 1998 Elsevier Science Ltd. All rights reserved.
• 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.