5-甲基-4-异噁唑甲酸乙酯 | 51135-73-0

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-甲基-4-异噁唑甲酸乙酯
• 中文别名: 5-甲基-4-异唑甲酸乙酯；5-甲基异噁唑-4-甲酸乙酯
• 英文名称: Ethyl 5-methyl-4-isoxazolecarboxylate
• 英文别名: 4-ethoxycarbonyl-5-methylisoxazole；ethyl 5-methylisoxazol-4-yl-carboxylate；ethyl 5-methylisoxazole-4-carboxylate；5-methylisoxazole-4-carboxylic acid ethyl ester；5-Methyl-isoxazol-carbonsaeure-(4)-aethylester；5-Methyl-isoxazol-4-carbonsaeure-aethylester；5-Methylisoxazol-4-carbonsaeureethylester；ethyl 5-methyl-1,2-oxazole-4-carboxylate
• CAS: 51135-73-0
• 化学式: C₇H₉NO₃
• 分子量: 155.153
• InChiKey: KOMSQTMQKWSQDW-UHFFFAOYSA-N

物化性质

• 熔点：
  49-52°C
• 沸点：
  95-97°C 15mm
• 密度：
  1.118 g/mL at 25 °C
• 闪点：
  95-97°C/15mm
• 溶解度：
  可溶于氯仿、甲醇
• 稳定性/保质期：

  如果按照规格使用和储存，则不会分解，未有已知危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S24/25,S26
• 危险类别码：
  R36/37/38
• 海关编码：
  2934999090
• WGK Germany：
  3
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  请将贮藏器密封保存，并存放在阴凉、干燥处。同时，确保工作环境具备良好通风或排气设施。

反应信息

• 作为反应物：
  描述：

  5-甲基-4-异噁唑甲酸乙酯 在 sodium ethanolate 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 12.0h， 以97%的产率得到2-氰基乙酰乙酸乙酯
  参考文献：
  名称：

  Schenone, Pietro; Fossa, Paola; Menozzi, Giulia, Journal of Heterocyclic Chemistry, 1991, vol. 28, # 2, p. 453 - 457

  摘要：

  DOI：
• 作为产物：
  描述：

  ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 在 羟胺 作用下， 以 甲醇 、 水 为溶剂， 以92.2%的产率得到5-甲基-4-异噁唑甲酸乙酯
  参考文献：
  名称：

  一种来氟米特的制备方法

  摘要：

  本发明涉及一种医药原料药来氟米特的制备新工艺，以乙酰乙酸乙酯为原料与盐酸羟胺环合得到来氟米特。该工艺不仅能够更好地控制来氟米特产品中3‑甲基异构体和4‑三氟甲基苯胺的含量，且产率更高，更加简洁。该工艺产生的工业废水废气少，更加绿色环保，可有效地降低生产成本和对设备的腐蚀。

  公开号：

  CN111233779B

文献信息

• Pharmaceutical compounds
  申请人：Lilly Industries Limited

  公开号：US04983619A1

  公开（公告）日：1991-01-08

  Compounds of the following formula have pharmaceutical properties: ##STR1## in which X is R'(HO)C.dbd.C(CN)--, R.sup.1 (CO)--CH(CN)-- or ##STR2## R.sup.1 and R.sup.2 are each hydrogen or C.sub.1-6 alkyl, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each hydrogen, hydroxy, halogen, nitro, cyano, carboxy, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, halo-substituted C.sub.1-4 alkyl, halo-substituted C.sub.1-4 alkoxy, halo-substituted C.sub.1-4 alkylthio, C.sub.2-5 alkoxycarbonyl, optionally substituted phenyl, optionally substituted phenoxy, R'R"N-- where R' and R" are each hydrogen or C.sub.1-4 alkyl or R'"CONH-- where R'" is C.sub.1-4 alkyl, or a group of the formula --CR.sup.7 R.sup.8 R.sup.9 in which R.sup.7, R.sup.8 and R.sup.9 are each C.sub.1-6 alkyl, halo-substituted C.sub.1-6 alkyl or optionally substituted phenyl, or R.sup.7 and R.sup.8, together with the carbon atom to which they are attached, form a cycloalkyl group containing 3 to 7 carbon atoms, or R.sup.7, R.sup.8 and R.sup.9 together with the carbon atom to which they are attached, form a bicycloalkyl group containing 4 to 9 carbon atoms, and Y is a 5- or 6-membered heterocyclic ring excluding pyrazole; and salts thereof.

  以下化合物具有药理特性：##STR1## 其中X为R'(HO)C.dbd.C(CN)--，R.sup.1 (CO)--CH(CN)--或##STR2## R.sup.1和R.sup.2分别为氢或C.sub.1-6烷基，R.sup.3、R.sup.4、R.sup.5和R.sup.6分别为氢、羟基、卤素、硝基、氰基、羧基、C.sub.1-4烷基、C.sub.1-4烷氧基、C.sub.1-4烷硫基、卤素取代的C.sub.1-4烷基、卤素取代的C.sub.1-4烷氧基、卤素取代的C.sub.1-4烷硫基、C.sub.2-5烷氧羰基、可选择取代的苯基、可选择取代的苯氧基、R'R"N--其中R'和R"分别为氢或C.sub.1-4烷基或R'"CONH--其中R'"为C.sub.1-4烷基，或具有以下式--CR.sup.7 R.sup.8 R.sup.9的基团，其中R.sup.7、R.sup.8和R.sup.9分别为C.sub.1-6烷基、卤素取代的C.sub.1-6烷基或可选择取代的苯基，或R.sup.7和R.sup.8与它们连接的碳原子一起形成含有3至7个碳原子的环烷基，或R.sup.7、R.sup.8和R.sup.9与它们连接的碳原子一起形成含有4至9个碳原子的双环烷基，Y为排除吡唑的5-或6-成员杂环环，以及其盐。
• Continuous flow chemistry: a discovery tool for new chemical reactivity patterns
  作者：Jan Hartwig、Jan B. Metternich、Nikzad Nikbin、Andreas Kirschning、Steven V. Ley

  DOI：10.1039/c4ob00662c

  日期：——

  Continuous flow chemistry as a process intensification tool is well known. However, its ability to enable chemists to perform reactions which are not possible in batch is less well studied or understood. Here we present an example, where a new reactivity pattern and extended reaction scope has been achieved by transferring a reaction from batch mode to flow. This new reactivity can be explained by

  作为过程增强工具的连续流化学是众所周知的。然而，其使化学家进行批量反应不可能的能力的研究或了解较少。在这里，我们提供一个示例，其中通过将反应从分批模式转移到流动模式，实现了新的反应模式和扩展的反应范围。这种新的反应性可以通过抑制回混和精确控制流动反应器装置中的温度来解释。
• Base-induced ring cleavage of 4-functionalized-3-unsubstituted isoxazoles. Synthesis of 5-aminoazoles and 4-cyanoazoles
  作者：A. Alberola、L. F. Antolin、A. M. Gonzalez、M. A. Laguna、F. J. Pulido

  DOI：10.1002/jhet.5570230414

  日期：1986.7

  The base-induced ring cleavage of 4-nitro-(Ia), 4-ethoxycarbonyl- (Ib) and 4-acetyl-5-methylisoxazole (Ic) and the conversion of the resulting β-cyanoenolates and β-enaminonitriles into 5-aminoazoles and 4-cyanoazoles was studied.

  4-硝基-（Ia），4-乙氧基羰基-（Ib）和4-乙酰基-5-甲基异恶唑（Ic）的碱诱导的环裂解以及所得的β-氰基烯酸酯和β-烯腈转化为5-氨基唑并研究了4-氰基唑。
• Process for preparing 5-methylisoxazole-4-carboxylic- (4'-trifluoromethyl)-anilide
  申请人：——

  公开号：US20030139606A1

  公开（公告）日：2003-07-24

  A process for preparing 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide comprising: (a) reacting ethylacetoacetate, triethylorthoformate, and acetic anhydride at a temperature of from about 75° C. to about 150° C., to form ethyl ethoxymethyleneacetoacetic ester; (b) combining the ethyl ethoxymethyleneacetoacetic ester with sodium acetate or a salt of trifluoroacetic acid in the presence of hydroxylamine sulfate at a temperature of from about −20° C. to 10° C., to form ethyl-5-methylisoxazole-4-carboxylate; (c) reacting the ethyl-5-methylisoxazole-4-carboxylate with a strong acid to form 5-methylisoxazole-4-carboxylic acid; (d) reacting the crystallized 5-methylisoxazole-4-carboxylic acid with thionyl chloride to form 5-methylisoxazole-4-carbonyl chloride; and (e) reacting the 5-methylisoxazole-4-carbonyl chloride with trifluoromethyl aniline and an amine base at a temperature of from about 0° C. to about 50° C. to form 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide. The process of the invention is especially advantageous for preparing 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide, since the process: (1) eliminates or reduces the formation of the by-product 2-cyanoacetoacetic-1-(4′-trifluoromethyl)-anilide (CATA), generally as low as 0.0006%; (2) eliminates or reduces the formation of isomeric impurity ethyl-3-methyisoxazole-4-carboxylate and its corresponding acid as low as 0.1%, (3) produces a high quality of 5-methylisoxazole-4-carboxylic-(4′-trifluoromethyl)-anilide generally having 99.8-100% HPLC potency; and (4) does not require distillation of the isoxazole ester.

  制备5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺的过程包括：(a)在约75°C至约150°C的温度下，将乙酰乙酸乙酯、三乙基正甲酸酯和乙酸酐反应，形成乙酸乙酯亚甲基乙酮乙酸酯；(b)将乙酸乙酯亚甲基乙酮乙酸酯与乙酸钠或三氟乙酸盐在氢氧胺硫酸存在下，在约-20°C至10°C的温度下反应，形成乙酸-5-甲基异噁唑-4-羧酸酯；(c)将乙酸-5-甲基异噁唑-4-羧酸酯与强酸反应，形成5-甲基异噁唑-4-羧酸；(d)将结晶的5-甲基异噁唑-4-羧酸与氯化亚硫酸形成5-甲基异噁唑-4-羰基氯化物；(e)将5-甲基异噁唑-4-羰基氯化物与三氟甲基苯胺和胺碱在约0°C至约50°C的温度下反应，形成5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺。该发明的过程特别有利于制备5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺，因为该过程：(1)消除或减少了副产物2-氰基乙酮乙酸-1-(4'-三氟甲基)-苯胺（CATA）的生成，通常低至0.0006%；(2)消除或减少了异构杂质乙酸-3-甲基异噁唑-4-羧酸酯及其对应酸的生成至0.1%；(3)产生高品质的5-甲基异噁唑-4-羧酸-(4'-三氟甲基)-苯胺，通常具有99.8-100%的HPLC纯度；(4)不需要对异噁唑酯进行蒸馏。
• Synthesis and In vivo Antifibrotic Activity of Novel Leflunomide Analogues
  作者：Abdelrahman Hamdi、Eman Said、Abdelbasset A. Farahat、Serry A. A. El-Bialy、Mohammed A. M. Massoud

  DOI：10.2174/1570180813666160630125624

  日期：2016.10.3

  Novel Leflunomide analogues were synthesized and evaluated in vivo against thioacetamide (TAA) induced liver fibrosis in rats. All the animals which were treated with the new analogues showed improved or comparable survival rates to those treated with Leflunomide. Animals which were treated with compounds 8d, 8e, 9 and 11 have shown improved liver parameters than Leflunomide treated animals. Histopathology

  合成了新型来氟米特类似物，并在体内针对硫代乙酰胺（TAA）诱导的大鼠肝纤维化进行了评估。与使用来氟米特治疗的动物相比，用新类似物治疗的所有动物均显示出提高的或相当的存活率。用化合物8d，8e，9和11治疗的动物显示出比来氟米特治疗的动物改善的肝脏参数。肝脏的组织病理学研究表明，化合物8a是活性最高的化合物，可将纤维化降低至最低水平，化合物8c，8e和11是纤维化评分为2-3的活性化合物，优于来氟米特。