1-溴-2-(氯甲基)-4-甲氧基苯 | 66192-25-4

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 芳香烃
• 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: 1-溴-2-(氯甲基)-4-甲氧基苯
• 英文名称: 2-bromo-5-methoxybenzyl chloride
• 英文别名: 2-bromo-2-methoxybenzyl chloride；2-bromo-5-methoxy-benzylchloride；4-bromo-2-chloromethylanisole；4-bromo-3-chloromethyl-anisole；Methyl-(4-brom-3-chlormethyl-phenyl)-aether；α-Chlor-6-brom-3-methoxy-toluol；1-bromo-2-(chloromethyl)-4-methoxyBenzene
• CAS: 66192-25-4
• 化学式: C₈H₈BrClO
• 分子量: 235.508
• InChiKey: XVDBQNMBIOIJLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-溴-2-(氯甲基)-4-甲氧基苯 在 盐酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 8.5h， 生成 (S)-2-methyl-3-(2'-bromo-5'-methoxyphenyl)propionic acid
  参考文献：
  名称：

  Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist

  摘要：

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.

  DOI：

  10.1021/jo991292t
• 作为产物：
  描述：

  3-甲氧基氯苄 在 吡啶 、 溴 作用下， 以 二氯甲烷 为溶剂， 反应 19.0h， 以77%的产率得到1-溴-2-(氯甲基)-4-甲氧基苯
  参考文献：
  名称：

  Piperidinylaminomethyl trifluoromethyl cyclic ether compounds as substance P antagonists

  摘要：

  这项发明提供了以下化合物及其药用可接受的盐： 1 其中R 1 为C 1 -C 6 烷基；R 2 为氢、C 1 -C 6 烷基、卤代C 1 -C 6 烷基或苯基；R 3 为氢或卤素；R 4 和R 5 独立地为氢、C 1 -C 6 烷基或卤代C 1 -C 6 烷基；n为一、二或三。 这些化合物可用作镇痛剂或抗炎药，或用于治疗心血管疾病、过敏性疾病、血管生成、中枢神经系统疾病、呕吐、胃肠道疾病、晒伤、尿失禁，或由幽门螺杆菌等引起的疾病、疾病或不良状况，尤其是在哺乳动物主体，特别是人类中。还公开了制备式(I)化合物的中间体。

  公开号：

  US20030208079A1

文献信息

• Practical Asymmetric Synthesis of a Selective Endothelin A Receptor (ETA) Antagonist
  作者：Zhiguo J. Song、Matthew Zhao、Lisa Frey、Jing Li、Lushi Tan、Cheng Y. Chen、David M. Tschaen、Richard Tillyer、Edward J. J. Grabowski、Ralph Volante、Paul J. Reider、Yoshiaki Kato、Shigemitsu Okada、Takayuki Nemoto、Hiroki Sato、Atsushi Akao、Toshiaki Mase

  DOI：10.1021/ol016601s

  日期：2001.10.1

  [structure: see text]. A practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2. This synthesis includes a new efficient process for the preparation of 6-bromo-2,3-dihydrobenzofuran, a stereoselective conjugate addition of an aryllithium followed by stereospecific addition of the Grignard reagent of the top aryl bromide

  [结构：见文字]。开发了一种实用的无色谱不对称合成方法，用于大规模制备内皮素受体拮抗剂2。该合成方法包括制备6-溴-2,3-二氢苯并呋喃的新有效方法，即芳基锂的立体选择性共轭加成。其次是立体定向添加顶部芳基溴的格氏试剂，以及氨基磷酸介导的立体定向分子内烯醇酸酯烷基化，这导致形成带有三个连续不对称中心的五元环。
• Synthesis of Polycyclic Isoindolines via α-C–H/N–H Annulation of Alicyclic Amines
  作者：Anirudra Paul、Camille Vasseur、Scott D. Daniel、Daniel Seidel

  DOI：10.1021/acs.orglett.2c00018

  日期：2022.2.11

  situ from their corresponding alicyclic amines via oxidation of their lithium amides with simple ketone oxidants, engage aryllithium compounds containing a leaving group on an ortho-methylene functionality to provide polycyclic isoindolines in a single operation. The scope of this transformation includes pyrrolidine, piperidine, azepane, azocane, and piperazines.

  相对不稳定的环状亚胺是通过用简单的酮氧化剂氧化其氨基锂而由相应的脂环胺原位生成的，与邻亚甲基官能团上含有离去基团的芳基锂化合物接合，在单一操作中提供多环异吲哚啉。该转化的范围包括吡咯烷、哌啶、氮杂环庚烷、氮佐烷和哌嗪。
• Nickel-Catalyzed Chemo- and Regioselective Benzylarylation of Unactivated Alkenes with <i>o</i>-Bromobenzyl Chlorides
  作者：Hailong Wang、Haichao Huang、Chao Gong、Yong Diao、Jianmei Chen、Si-Hai Wu、Lianhui Wang

  DOI：10.1021/acs.orglett.1c03991

  日期：2022.1.14

  Chemo- and regioselectively nickel-catalyzed reductive benzylarylation of unactivated alkenes with o-bromobenzyl chlorides is disclosed herein, in which electrophiles participate through a single-component double-site approach. Moreover, its utility is underscored by the concise synthesis of bioactive Indane compounds and postreaction functionalizations leading to structurally diverse scaffolds. Preliminary

  本文公开了化学和区域选择性镍催化的未活化烯烃与邻溴苄基氯的还原苄基化反应，其中亲电试剂通过单组分双位点方法参与。此外，生物活性茚满化合物的简明合成和导致结构多样化的支架的反应后功能化强调了它的实用性。初步的机理研究表明存在自由基链式反应机制。
• Process for the synthesis of an endothelin receptor antagonist
  申请人：——

  公开号：US20020107391A1

  公开（公告）日：2002-08-08

  The present invention relates to a practical and efficient way to synthesize the compound for the endothelin receptor antagonist involving a Grignard addition and a cyclization reaction to give a desired compound of the general formula shown below: 1

  本发明涉及一种实用高效的合成内皮素受体拮抗剂化合物的方法，涉及格氏试剂加成和环化反应，以得到下面所示的一般式的目标化合物：1
• Synthesis of enantiopure B-nor-steroids by multiple Pd-catalyzed transformations
  作者：Lutz F Tietze、J Matthias Wiegand、Carsten Vock

  DOI：10.1016/s0022-328x(03)00720-4

  日期：2003.12

  The synthesis of the novel enantiopure B-nor-steroid 9 is described employing a combination of a Suzuki- and a Heck-reaction. As substrates the 2-bromobenzylchloride (11) and the boronic ester 16 were used; the latter was prepared from the Hajos–Wiechert ketone derivative 17 in five steps. Noteworthy, the Heck-reaction was performed under microwave irradiation, which was much superior compared to the

  描述了新的对映体纯的B-nor-类固醇9的合成，其结合了Suzuki-反应和Heck-反应。使用2-溴苄基氯（11）和硼酸酯16作为底物；后者是由Hajos-Wiechert酮衍生物17分五步制备的。值得注意的是，赫克反应是在微波辐射下进行的，这比正常的热反应要好得多。所述工作的目的是设计新型雌激素，其结合至位于内皮表面上的最大K +通道的β-单元，而未显示雌二醇6的激素活性。