N-(2-hydroxyl-1,1-dimethylethyl) 4-[1-(1,3-dioxolanyl)-ethyl]-5-methyl-isoxazole-3-carboxamide | 213383-63-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(2-hydroxyl-1,1-dimethylethyl) 4-[1-(1,3-dioxolanyl)-ethyl]-5-methyl-isoxazole-3-carboxamide
• 英文别名: N-(2-hydroxy-1,1-dimethyl)-5-methyl-4-(2-methyl-1,3-dioxolan-2-yl)-3-isoxazolecarboxamide；N-(1-hydroxy-2-methylpropan-2-yl)-5-methyl-4-(2-methyl-1,3-dioxolan-2-yl)-1,2-oxazole-3-carboxamide
• CAS: 213383-63-2
• 化学式: C₁₃H₂₀N₂O₅
• 分子量: 284.312
• InChiKey: XKLOJLPOAMOQMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  93.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxyl-1,1-dimethylethyl) 4-[1-(1,3-dioxolanyl)-ethyl]-5-methyl-isoxazole-3-carboxamide 在 四氯化碳 、 三乙胺 、 三苯基膦 作用下， 以 乙腈 为溶剂， 以82%的产率得到3-(4,4-dimethyl-5H-1,3-oxazol-2-yl)-5-methyl-4-(2-methyl-1,3-dioxolan-2-yl)-1,2-oxazole
  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
• 作为产物：
  描述：

  3-isoxazolecarboxylic acid 5-methyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)-ethyl ester 在 正丁基锂 、 samarium(III) chloride 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 丙酮 、 苯 为溶剂， 生成 N-(2-hydroxyl-1,1-dimethylethyl) 4-[1-(1,3-dioxolanyl)-ethyl]-5-methyl-isoxazole-3-carboxamide
  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

• Lanthanide Catalyzed Synthesis of β-Hydroxyl Amides
  作者：P. Zhou、N. R. Natale

  DOI：10.1080/00397919808004440

  日期：1998.9

  Abstract Lanthanide (III) chloride improved the reaction of carboxylic esters with β-amino alkoxides (generated in situ from β-amino alcohols) and produced β-hydroxyl amides under mild conditions, and in high yields.

  摘要 镧系元素 (III) 氯化物改进了羧酸酯与 β-氨基醇盐（由 β-氨基醇原位生成）的反应，并在温和的条件下以高产率制备了 β-羟基酰胺。
• 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.