2-溴丁酸苄酯 | 42115-51-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-溴丁酸苄酯
• 英文名称: benzyl 2-bromobutanoate
• 英文别名: benzyl 2-bromobutyrate
• CAS: 42115-51-5
• 化学式: C₁₁H₁₃BrO₂
• 分子量: 257.127
• InChiKey: IAWWKWVHVUNYFP-UHFFFAOYSA-N

物化性质

• 沸点：
  110-115 °C
• 密度：
  1.361±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-溴丁酸苄酯 在 吡啶 、 碘 、 锌 、 三氯氧磷 作用下， 以 苯 为溶剂， 生成 4-(2-Benzyloxycarbonyl-1-chloro-butyl)-benzoic acid methyl ester
  参考文献：
  名称：

  Synthesis and antifolate properties of 9-alkyl-10-deazaminopterins

  摘要：

  Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogenation to the aminomethyl ketone (8a). Direct N-alkylation by 2,4-diamino-5-nitro-6-chloropyrimidine followed by reductive ring closure in Zn-HOAc and subsequent saponification of the benzoate ester yielded 4-amino-4-deoxy-9-methyl-10-deazapteroic acid (11a). Coupling with diethyl L-glutamate and saponification afforded 9-methyl-10-deazaminopterin (13a). The 9-ethyl analogue (13b) was similarly prepared from benzyl 2-bromobutyrate. The 9-methyl analogue (13a) was 21 times more potent than MTX as an inhibitor of cell growth in L1210 cells. The reason for this enhanced cytotoxicity in L1210 is unclear, since enzyme inhibition and transport parameters were similar to those of MTX. In human Manca leukemia cells growth inhibition was not dramatic and paralleled MTX.

  DOI：

  10.1021/jm00163a035
• 作为产物：
  描述：

  2-溴丁酰溴 、 苯甲醇 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以76%的产率得到2-溴丁酸苄酯
  参考文献：
  名称：

  Pd/P,P=O 体系催化吲哚与α-溴酯的区域选择性2-烷基化反应

  摘要：

  通过使用 P,P=O 配体开发了钯催化的吲哚与 α-溴酯的 2-烷基化反应。该方法具有优异的区域选择性、温和的反应条件和良好的官能团相容性。P,P=O 配体以及 4Å 分子筛的使用对于转化的成功至关重要。机理研究表明反应通过自由基途径进行。

  DOI：

  10.1016/j.cclet.2021.06.091

文献信息

• The Hydrolysis of Esters Related to <i>O</i>-Hippuryl-2-hydroxybutanoic Acid by Carboxypeptidase A
  作者：John W. Bunting、Joe Murphy

  DOI：10.1139/v74-385

  日期：1974.7.15

  The hydrolysis of each of the following esters by bovine carboxypeptidase A has been studied at pH 7.5, 25°, ionic strength 0.5: O-hippuryl-, O-phenaceturyl-, O-aceturyl-, O-(N-methylhippuryl)-, and O-(N-hippurylglycyl)-2-hydroxybutanoic acids, and 2-(3-benzoylpropanoxy)-, 2-benzoxyacetoxy-, and 2-(4-phenylbutanoxy)butanoic acids. Substrate inhibition occurs with only the hippuric and phenaceturic acid esters and in the six other cases simple Michaelis–Menten kinetics are observed. The relatively minor variations in the structures of the acid moieties of these esters lead to quite large variations in K_m, although k_cat seems to be relatively independent of the nature of the acid moiety. Binding modes of substrate molecules at both the catalytic and inhibitory sites are discussed in the light of these observations.

  以下酯化物在pH 7.5、25°C、离子强度为0.5条件下，通过牛羧肽酶A的水解已经被研究：O-香豆酰基、O-苯乙酰基、O-乙酰基、O-(N-甲基香豆酰基)、O-(N-香豆酰甘氨酰)-2-羟基丁酸，以及2-(3-苯甲酰基丙酰氧基)-、2-苯甲酰基乙酸氧基-和2-(4-苯基丁酰氧基)丁酸。只有香豆酸和苯乙酸酯发生底物抑制，在其他六种情况下观察到简单的米氏-门特氏动力学。这些酯的酸基结构相对较小的变化导致Km有相当大的变化，尽管kcat似乎与酸基的性质相对独立。在这些观察结果的光下，讨论了底物分子在催化和抑制位点的结合模式。
• Cobalt–Bisoxazoline-Catalyzed Asymmetric Kumada Cross-Coupling of Racemic α-Bromo Esters with Aryl Grignard Reagents
  作者：Jianyou Mao、Feipeng Liu、Min Wang、Lin Wu、Bing Zheng、Shangzhong Liu、Jiangchun Zhong、Qinghua Bian、Patrick J. Walsh

  DOI：10.1021/ja5109084

  日期：2014.12.17

  The first cobalt-catalyzed asymmetric Kumada cross-coupling with high enantioselectivity has been developed. The reaction affords a unique strategy for the enantioselective arylation of α-bromo esters catalyzed by a cobalt-bisoxazoline complex. A variety of chiral α-arylalkanoic esters were prepared in excellent enantioselectivity and yield (up to 97% ee and 96% yield). The arylated products were transformed

  已经开发出第一个具有高对映选择性的钴催化的不对称 Kumada 交叉偶联。该反应为钴-双恶唑啉配合物催化的α-溴酯的对映选择性芳基化提供了独特的策略。以优异的对映选择性和产率（高达 97% ee 和 96% 产率）制备了多种手性 α-芳基链烷酸酯。芳基化产物在没有ee侵蚀的情况下转化为α-芳基羧酸和伯醇。本文合成的新的对映体富集的 α-芳基丙酸酯有可能用于非甾体抗炎药的开发。该方法以克级规模进行，并应用于高度对映体富集的 (S)-非诺洛芬和 (S)-ar-姜黄酮的合成。
• Cobalt-Bisoxazoline-Catalyzed Enantioselective Cross-Coupling of α-Bromo Esters with Alkenyl Grignard Reagents
  作者：Yun Zhou、Lifeng Wang、Gucheng Yuan、Shikuo Liu、Xiao Sun、Chaonan Yuan、Yuxiong Yang、Qinghua Bian、Min Wang、Jiangchun Zhong

  DOI：10.1021/acs.orglett.0c01557

  日期：2020.6.5

  cobalt-bisoxazoline catalyst and afforded various α-alkyl-β,γ-unsaturated esters with excellent enantioselectivities and moderate to good yields (≤95% ee and ≤82% yields). The formal synthesis of the California red scale pheromone using this method was investigated, and radical clock experiments were performed.

  已经开发出有机卤化物与烯基格氏试剂的第一催化不对称熊田交叉偶联反应。用钴-双恶唑啉催化剂促进反应，得到各种α-烷基-β，γ-不饱和酯，其具有优异的对映选择性和中等至良好的收率（≤95％ee和≤82％收率）。研究了使用这种方法的加利福尼亚红标信息素的形式合成，并进行了自由基时钟实验。
• [EN] PROTECTED ORGANOBORONIC ACIDS WITH TUNABLE REACTIVITY, AND METHODS OF USE THEREOF<br/>[FR] ACIDES ORGANOBORONIQUES PROTÉGÉS À RÉACTIVITÉ AJUSTABLE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV ILLINOIS

  公开号：WO2017027435A1

  公开（公告）日：2017-02-16

  Disclosed are a range of protected organoboronic acid reagents useful in the modular assembly of complex organic compounds. The reactivities of the protected organoboronic acid reagents may be varied predictably by changes to the number and identities of their substituents. Also disclosed are methods of using the protected organoboronic acid reagents in the synthesis of organic compounds.

  本文披露了一系列受保护的有机硼酸试剂，可用于复杂有机化合物的模块化组装。这些受保护的有机硼酸试剂的反应性可以通过改变它们的取代基的数量和身份来可预测地变化。同时还披露了在有机化合物的合成中使用这些受保护的有机硼酸试剂的方法。
• Novel ibuprofen prodrugs with improved pharmacokinetics and non-ulcerogenic potential
  作者：Valmik D. Dhakane、Hemant V. Chavan、Vishnu N. Thakare、Laxman K. Adsul、Sadanand N. Shringare、Babasaheb P. Bandgar

  DOI：10.1007/s00044-013-0639-8

  日期：2014.1

  anti-inflammatory activity with pharmacokinetic, ulcerogenic properties of various synthesized prodrugs of ibuprofen in experimental animals. Prodrugs 2, 6, 9, 10, 12, and 14 were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ibuprofen 1a in both normal and inflammation-induced rats. Metabolic stability of prodrugs 2, 6, 9, 10, 12, and 14 were

  在本研究中，我们评估了布洛芬各种合成前药在实验动物中的抗炎活性和药代动力学，致溃疡性。发现在正常和炎症诱导的大鼠中，前药2、6、9、10、12和14具有比标准药物布洛芬1a显着的抗炎活性，几乎没有致溃疡的潜力。前药的代谢稳定性2，6，9，10，12，和14还对大鼠肝微粒体进行了研究，并通过估计在不同时间间隔下这些前药的曲线下面积（AUC）和血浆浓度来确定口服生物利用度。实验结果在第1和2小时引起较高的AUC和血浆浓度，表明与亲本布洛芬相比，口服生物利用度提高。发现这些前药具有最小的胃溃疡，并保留了在实验动物中观察到的抗炎活性。因此，目前的实验结果表明，抗炎药布洛芬酯前药的致溃疡潜力最小，各种药代动力学特性有了显着改善。