4-(甲氧羰基)双环[2.2.2]辛烷-1-羧酸 | 18720-35-9

• 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 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 4-(甲氧羰基)双环[2.2.2]辛烷-1-羧酸
• 中文别名: 4-(甲氧羰基)双环[2.2.2]辛烷-1-甲酸；二环[2,2,2]辛烷-1,4-环己二羧酸单甲酯；双环[2.2.2]辛烷-1,4-二羧酸单甲酯；二环【2,2,2】辛烷-1,4-环己二羧酸单甲酯
• 英文名称: bicyclo[2.2.2]octane-1,4-dicarboxylic acid monomethyl ester
• 英文别名: 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid；4-carbomethoxybicyclo<2.2.2>octane-1-carboxylic acid；4-methoxycarbonylbicyclo[2.2.2]octane-1-carboxylic acid
• CAS: 18720-35-9
• 化学式: C₁₁H₁₆O₄
• mdl: MFCD18459359
• 分子量: 212.246
• InChiKey: KBZVAQVEHVGIEI-UHFFFAOYSA-N

物化性质

• 熔点：
  186.0 to 190.0 °C
• 沸点：
  322.5±42.0 °C(Predicted)
• 密度：
  1.307±0.06 g/cm3(Predicted)
• 溶解度：
  溶于甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.818
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2918990090
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P301+P310+P330,P305+P351+P338
• 危险品运输编号：
  2811
• 危险性描述：
  H301,H319
• 储存条件：
  温度：2~8°C，保持在惰性气体氛围中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 4-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid
CAS number: 18720-35-9

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C11H16O4
Molecular weight: 212.2

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

性质：熔点为180-182℃，白色晶体。

用途：二环[2.2.2]辛烷-1,4-二羧酸单甲酯是一种重要的精细化工中间体，可用于合成香料、液晶材料等多种功能化合物，同时也适用于药物及药物中间体的生产。

反应信息

• 作为反应物：
  描述：

  4-(甲氧羰基)双环[2.2.2]辛烷-1-羧酸 在 4-二甲氨基吡啶 、 N-氯代丁二酰亚胺 、 lithium aluminium tetrahydride 、 氯化亚砜 、 盐酸羟胺 、 sodium carbonate 、 戴斯-马丁氧化剂 、 乙二醇 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.66h， 生成 3-[bicyclo[2.2.2]octan-1-yl]-5-cyclopropyl-1,2-oxazole-4-carboxylic acid
  参考文献：
  名称：

  [EN] HORMONE RECEPTOR MODULATORS FOR TREATING METABOLIC CONDITIONS AND DISORDERS
  [FR] MODULATEURS DU RÉCEPTEUR HORMONAL POUR LE TRAITEMENT D'ÉTATS ET DE TROUBLES MÉTABOLIQUES

  摘要：

  这项发明涉及FXR的激活剂，可用于治疗自身免疫性疾病、肝病、肠道疾病、肾脏疾病、癌症以及FXR在其中发挥作用的其他疾病，其化学式为(I)：(I)，其中L1、A、X1、X2、R1、R2和R3如本文所述。

  公开号：

  WO2018039386A1
• 作为产物：
  描述：

  dimethyl 2,5-bi<1,3>dithiolanylbicyclo<2.2.2>octane-1,4-dicarboxylate 在 Raney nickel-W₂ 氢氧化钾 、 乙醇 作用下， 以 甲醇 、 水 为溶剂， 反应 120.0h， 生成 4-(甲氧羰基)双环[2.2.2]辛烷-1-羧酸
  参考文献：
  名称：

  Rodlike Molecules by Kolbe Electrolysis

  摘要：

  描述了一种新的简短且简单的方法，以获得刚性、棒状的碳氢骨架，特别是寡碱基[2.2.2]八烷类型。关键步骤是二环和三环羧酸的桥头位置之间的电化学C-C键偶联反应。功能团可以保留，并且它们会影响C-C键连接的产率。通过这种方法，以往难以或繁琐的合成过程得以缩短，同时刚性、不可崩溃的纳米级间隔单元也变得容易获取。优化后的电化学程序进行了详细描述。

  DOI：

  10.1055/s-1996-4152

文献信息

• A general N-alkylation platform via copper metallaphotoredox and silyl radical activation of alkyl halides
  作者：Nathan W. Dow、Albert Cabré、David W.C. MacMillan

  DOI：10.1016/j.chempr.2021.05.005

  日期：2021.7

  The catalytic union of amides, sulfonamides, anilines, imines, or N-heterocycles with a broad spectrum of electronically and sterically diverse alkyl bromides has been achieved via a visible-light-induced metallaphotoredox platform. The use of a halogen abstraction-radical capture (HARC) mechanism allows for room temperature coupling of C(sp3)-bromides using simple Cu(II) salts, effectively bypassing

  通过可见光诱导的金属光氧化还原平台实现了酰胺、磺胺、苯胺、亚胺或N-杂环与广谱电子和空间多样化烷基溴的催化结合。卤素提取-自由基捕获 (HARC) 机制的使用允许使用简单的 Cu(II) 盐在室温下耦合 C( sp 3 )-溴化物，有效绕过通常与热诱导 S N 2 或 S相关的过高障碍N 1 N-烷基化。这种区域和化学选择性方案与 >10 类药物相关的N兼容- 亲核试剂，包括已建立的药剂，以及结构多样的伯、仲和叔烷基溴。此外，通过将N-亲核试剂与环丙基溴和未活化的烷基氯（与亲核取代途径不相容的底物）结合，突出了 HARC 方法与传统惰性偶联伙伴结合的能力。初步的机械实验验证了该平台的双重催化、开壳性质，这使得在传统的基于卤化物的N-烷基化系统中无法实现的反应性成为可能。
• Generation and Cross-Coupling of Organozinc Reagents in Flow
  作者：Ananda Herath、Valentina Molteni、Shifeng Pan、Jon Loren

  DOI：10.1021/acs.orglett.8b03156

  日期：2018.12.7

  formation of organozinc reagents and subsequent cross-coupling with aryl halides and activated carboxylic acids is reported. Formation of organozinc reagents is achieved by pumping organic halides, in the presence of ZnCl2 and LiCl, through an activated Mg-packed column under flow conditions. This method provides efficient in situ formation of aryl, primary, secondary, and tertiary alkyl organozinc reagents

  报道了一种通用的流动合成方法，用于原位形成有机锌试剂，然后与芳基卤化物和活化的羧酸进行交叉偶联。有机锌试剂的形成是通过在流动条件下将有机卤化物在ZnCl 2和LiCl的存在下泵送通过活化的Mg填充柱来实现的。该方法可有效地原位形成芳基，伯，仲和叔烷基有机锌试剂，随后将其在下游进行Negishi或脱羧Negishi交叉偶联反应的伸缩。所描述的方法提供了使用有机锌试剂获得各种C–C键的方法，这些试剂否则在商业上是不可用的，或者在传统的间歇反应条件下难以制备。
• Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes
  作者：Yi Jiang、Jiaoting Pan、Tao Yang、Yu Zhao、Ming Joo Koh

  DOI：10.1016/j.chempr.2020.12.024

  日期：2021.4

  that the synthesis of stereodefined 1,3-enynes featuring a trisubstituted olefin is achieved by merging alkynes, alkynyl bromides, and redox-active N-(acyloxy)phthalimides through nickel-catalyzed reductive alkylalkynylation. Products are generated in up to an 89% yield as single regio- and E isomers. Transformations are tolerant of diverse functional groups and the resulting 1,3-enynes are amenable

  通过正交活化容易获得的底物进行炔烃的流线型双官能化开发催化多组分反应是有机化学中一个引人注目的目标。尤其是炔烃羰基化可以直接进入具有不同取代模式的有价值的1,3-烯炔。在这里，我们显示了通过合并炔烃，炔基溴化物和氧化还原活性的N-（酰氧基）邻苯二甲酰亚胺，通过镍催化的还原性烷基炔基化反应，可以合成具有三取代烯烃的立体定义的1,3-烯炔。单一区域和E生成的产品产率高达89％异构体。转化耐受各种官能团，并且所得的1，3-烯炔适合进一步加工成合成上有用的结构单元。利用烯烃系的N-（酰氧基）邻苯二甲酰亚胺，可以实施级联自由基加成/环化/炔基化方法以获得1，5-烯炔。这项研究强调了氧化还原活性酯与卤代烷烃相比在还原性炔烃双碳官能化中作为优越的烷基供体的关键作用。
• Organocatalytic decarboxylative alkylation of <i>N</i>-hydroxy-phthalimide esters enabled by pyridine-boryl radicals
  作者：Liuzhou Gao、Guoqiang Wang、Jia Cao、Dandan Yuan、Cheng Xu、Xuewen Guo、Shuhua Li

  DOI：10.1039/c8cc06152a

  日期：——

  The decarboxylative alkylation of N-hydroxyphthalimide (NHPI) based reactive esters with olefins has been achieved via an organocatalytic strategy. Control experiments and density functional theory calculations suggest that these reactions involve a boryl-radical mediated decarboxylation pathway, which is different from the single electron transfer involved in decarboxylative alkylation reactions reported

  N-羟基邻苯二甲酰亚胺（NHPI）基反应性酯与烯烃的脱羧烷基化已通过有机催化策略实现。对照实验和密度泛函理论计算表明，这些反应涉及硼基自由基介导的脱羧途径，该途径不同于先前报道的脱羧烷基化反应中涉及的单电子转移。这种无金属的脱羧烷基化反应具有良好的功能相容性，并且通过烷基和芳基羧酸衍生物的转化说明了广泛的底物范围。
• Organophotoredox-Catalyzed Formation of Alkyl–Aryl and −Alkyl C–S/Se Bonds from Coupling of Redox-Active Esters with Thio/Selenosulfonates
  作者：Yue Dong、Peng Ji、Yueteng Zhang、Changqing Wang、Xiang Meng、Wei Wang

  DOI：10.1021/acs.orglett.0c03624

  日期：2020.12.18

  A mild organophotoredox synthetic protocol for forming a Csp3–S/Se bond by reacting widespread redox-active esters with thio/selenosulfonates has been developed. The power of the synthetic manifold is fueled by an unprecedented broad substrate scope and wide functional group tolerance.

  已经开发出一种温和的有机光氧化还原合成方案，通过使广泛的氧化还原活性酯与硫代/硒磺酸盐反应形成 C sp 3 –S/Se 键。前所未有的广泛底物范围和广泛的官能团耐受性推动了合成歧管的力量。