4-溴苯乙酸甲酯 | 41841-16-1

• 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 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-溴苯乙酸甲酯
• 中文别名: 对溴苯乙酸甲酯；4-溴苯基醋酸甲酯
• 英文名称: (4-bromo-phenyl)-acetic acid methyl ester
• 英文别名: methyl 4-bromophenylacetate；methyl 2-(4-bromophenyl)acetate；methyl p-bromophenylacetate
• CAS: 41841-16-1
• 化学式: C₉H₉BrO₂
• mdl: MFCD00126844
• 分子量: 229.073
• InChiKey: QHJOWSXZDCTNQX-UHFFFAOYSA-N

物化性质

• 熔点：
  113-114 °C
• 沸点：
  138-140 °C(Press: 13 Torr)
• 密度：
  1.445±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  29163990
• 危险性防范说明：
  P305+P351+P338
• 危险性描述：
  H227,H315,H319,H335
• 储存条件：
  2~8°C

SDS

Name:	Methyl 4-bromophenylacetate Material Safety Data Sheet
Synonym:
CAS:	41841-16-1

Section 1 - Chemical Product MSDS Name:Methyl 4-bromophenylacetate Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
41841-16-1	Methyl 4-bromophenylacetate		unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Not available.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
May cause respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Absorb spill with inert material (e.g. vermiculite, sand or earth), then place in suitable container.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 41841-16-1: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Liquid
Color: Not available.
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: 105 deg C @15mmHg
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C9H9BrO2
Molecular Weight: 229.02

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, carbon dioxide, hydrogen bromide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 41841-16-1 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Methyl 4-bromophenylacetate - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 41841-16-1: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 41841-16-1 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 41841-16-1 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

化学反应

4-溴苯乙酸甲酯具有多种反应性，能够参与许多化学转化，例如甲基化、羰基化和甲氧基羰基化。此外，它还能替代常规试剂，如碘甲烷、硫酸二甲酯和光气。

应用

作为绿色反应试剂，4-溴苯乙酸甲酯在有机合成中有着广泛的应用，能够实现多种官能团的转化，用于可再生生物基衍生物的升级和增值。通常，它同时充当反应物和可循环使用的反应介质，避免使用其他有毒溶剂或石化来源的溶剂。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  对溴苯乙酸	2-(4-bromophenyl)-acetic acid	1878-68-8	C8H7BrO2	215.046
  4-溴苯乙酰氯	2-(4-bromophenyl)acetyl chloride	37859-24-8	C8H6BrClO	233.492
  对溴苯乙腈	4-Bromophenylacetonitrile	16532-79-9	C8H6BrN	196.046

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  对溴苯乙酸	2-(4-bromophenyl)-acetic acid	1878-68-8	C8H7BrO2	215.046
  2-(4-溴苯基)乙酸叔丁酯	tert-butyl 2-(4-bromophenyl)acetate	33155-58-7	C12H15BrO2	271.154
  1-溴-4-(2-甲氧基乙基)苯	1-bromo-4-(2-methoxyethyl)benzene	60835-90-7	C9H11BrO	215.09
  2-(4-溴苯基)丙酸甲酯	methyl 2-(4-bromophenyl)propanoate	83636-46-8	C10H11BrO2	243.1
  ——	methyl 2-(4-(2-hydroxyethyl)phenyl)acetate	129506-80-5	C11H14O3	194.23
  4-溴苯乙醇	4-bromophenethanol	4654-39-1	C8H9BrO	201.063
  ——	methyl 2-(4-bromophenyl)-2-hydroxyacetate	127709-20-0	C9H9BrO3	245.073
  4-溴苯乙醛	p-bromophenylacetaldehyde	27200-79-9	C8H7BrO	199.047
  2-(4-溴苯基)丙酸	2-(4-bromophenyl)propionic acid	53086-53-6	C9H9BrO2	229.073
  ——	methyl 2-bromo-2-(4-bromophenyl)acetate	129592-90-1	C9H8Br2O2	307.969

反应信息

• 作为反应物：
  描述：

  4-溴苯乙酸甲酯 在 titanium(IV) tetraethanolate 、 sodium tetrahydroborate 、 potassium tert-butylate 、 potassium carbonate 、 对甲苯磺酸 、 copper(I) bromide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.5h， 生成 尼拉帕尼
  参考文献：
  名称：

  PARP抑制剂关键中间体及其制备方法

  摘要：

  本发明公开了一种PARP抑制剂Niraprib的制备方法以及该制备方法中使用的两个关键中间体，该制备方法以4‑溴苯乙酸甲酯和(S)‑叔丁基亚磺酰胺为原料，经过缩合、不对称烷基化、还原、偶联得到关键中间体化合物5；化合物5经缩合偶联得到化合物6；化合物6在对甲苯磺酸作用下水解脱除保护基，得到目标产物Niraprib。本发明的有益效果是：通过引入手性辅剂的不对称烷基化诱导手性，克服了已有的拆分和手性源方法，该法操作简单，条件温和，收率良好，化学纯度和光学纯度均较高，且关键的中间体5和SM3缩合制得目标化合物1，突破原研专利，适合于工业化生产。

  公开号：

  CN108997313A
• 作为产物：
  描述：

  对溴苯乙酸 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-溴苯乙酸甲酯
  参考文献：
  名称：

  以高比活性合成 3H 标记的 5-HT3 拮抗剂 (RS-25259-197)

  摘要：

  描述了标题化合物、具有止吐特性的选择性 5-HT 3 拮抗剂的制备。涉及的关键中间体是 6-溴-1,2-二氢萘甲酸 (5)，它是由 4-溴苯乙酸通过迈克尔加成、酸诱导环化、还原和脱水合成的。选择化合物 (5) 是因为它有两个标记位点以确保最终产品的高比活性。用无载体氚气还原酰胺 6，然后用 BF 3 -OEt 2 还原酰胺官能团并进行分子内环化，得到比活性为 70.4 Ci/mmol 和 >99% 纯度的标题化合物。

  DOI：

  10.1002/(sici)1099-1344(199605)38:5<425::aid-jlcr860>3.0.co;2-b

文献信息

• [EN] POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES<br/>[FR] COMPOSÉS POLYCYCLIQUES ET MÉTHODES POUR LA DÉGRADATION CIBLÉE DE POLYPEPTIDES DU FIBROSARCOME RAPIDEMENT ACCÉLÉRÉ
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2020051564A1

  公开（公告）日：2020-03-12

  The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物ULM—L—PTM，其作为快速加速纤维肉瘤（RAF，如c-RAF、A-RAF和/或B-RAF；目标蛋白）的调节剂具有实用性。具体而言，本公开涉及含有一端结合到相应E3泛素连接酶的Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源物2配体的双功能化合物，另一端结合到目标蛋白RAF的部分，使得目标蛋白与泛素连接酶靠近，以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白的聚集或积累，或目标蛋白的构成性激活导致的疾病或紊乱。
• Synthesis of Ketones and Esters from Heteroatom-Functionalized Alkenes by Cobalt-Mediated Hydrogen Atom Transfer
  作者：Xiaoshen Ma、Seth B. Herzon

  DOI：10.1021/acs.joc.6b01709

  日期：2016.10.7

  Cobalt bis(acetylacetonate) is shown to mediate hydrogen atom transfer to a broad range of functionalized alkenes; in situ oxidation of the resulting alkylradical intermediates, followed by hydrolysis, provides expedient access to ketones and esters. By modification of the alcohol solvent, different alkyl ester products may be obtained. The method is compatible with a number of functional groups including

  已显示双（乙酰丙酮酸）钴介导氢原子转移到各种官能化烯烃中。所得烷基自由基中间体的原位氧化，然后水解，可方便地获得酮和酯。通过改性醇溶剂，可以获得不同的烷基酯产物。该方法与许多官能团兼容，包括链烯基卤化物，硫化物，三氟甲磺酸酯和膦酸酯，为乙烯基硅烷的Tamao-Fleming氧化和Arndt-Eistert同系物提供了温和而实用的替代方法。
• Hydrodebromination of Aromatic Bromides Catalyzed by Unsupported Nanoporous Gold: Heterolytic Cleavage of Hydrogen Molecule
  作者：Yuhui Zhao、Xiujuan Feng、Sheng Zhang、Yoshinori Yamamoto、Ming Bao

  DOI：10.1002/cctc.202000674

  日期：2020.10.6

  Unsupported nanoporous gold (AuNPore) is a highly efficient, practically applicable, and recyclable catalyst for hydrodebromination of aromatic bromides. The AuNPore‐catalyzed hydrodebromination of aromatic bromides proceeded smoothly at relatively low hydrogen pressure and temperature to achieve good to excellent yields of the corresponding non‐bromine variants. The selective hydrodebromination reaction

  无载体纳米多孔金（AuNPore）是一种高效，实用且可回收的催化剂，可用于芳族溴化物的加氢脱溴。AuNPore催化的芳族溴化物加氢脱溴反应在相对较低的氢气压力和较低温度下进行得很顺利，从而获得了相应的非溴化变体的良好或优异的收率。选择性加氢脱溴反应仅在氯原子共存时发生。首次的机理研究表明，H-H键以异解的方式在AuNPore表面分裂，生成Au-H氢化物。
• Room Temperature Coupling of Aryldiazoacetates with Boronic Acids Enhanced by Blue Light Irradiation
  作者：Amanda F. Silva、Marco A. S. Afonso、Rodrigo A. Cormanich、Igor D. Jurberg

  DOI：10.1002/chem.201905812

  日期：2020.5.4

  visible-light-promoted photochemical protocol is reported for the coupling of aryldiazoacetates with boronic acids. This photochemical reaction shows great enhancement compared to the same protocol performed in the absence of light. Except for a few cases, the room temperature coupling in the dark (thermal process) generally does not work. When it does, it is likely to also involve free carbenes as key intermediates

  据报道可见光促进的光化学方案用于芳基重氮乙酸酯与硼酸的偶联。与没有光照的相同方案相比，这种光化学反应显示出极大的增强。除少数情况外，在黑暗（热过程）中的室温耦合通常不起作用。如果这样做的话，很可能还涉及到游离卡宾作为关键中间体。可替代地，光化学反应显示出广泛的范围，可以在空气中进行并且耐受各种各样的官能团。反应进化监测，DFT计算和控制实验已用于评估这种复杂机制的主要方面。具有生物活性的分子阿迪芬，苯那西嗪和阿普生已经被制备为合成应用的实例。
• Macrolide Synthesis through Intramolecular Oxidative Cross-Coupling of Alkenes
  作者：Bing Jiang、Meng Zhao、Shu-Sen Li、Yun-He Xu、Teck-Peng Loh

  DOI：10.1002/anie.201710601

  日期：2018.1.8

  A RhIII‐catalyzed intramolecular oxidative cross‐coupling between double bonds for the synthesis of macrolides is described. Under the optimized reaction conditions, macrocycles containing a diene moiety can be formed in reasonable yields and with excellent chemo‐ and stereoselectivity. This method provides an efficient approach to synthesize macrocyclic compounds containing a 1,3‐conjugated diene

  描述了用于大环内酯合成的双键之间的Rh III催化的分子内氧化交叉偶联。在优化的反应条件下，可以以合理的收率形成具有二烯部分的大环，并具有出色的化学和立体选择性。该方法为合成包含1,3-共轭二烯结构的大环化合物提供了一种有效的方法。