2-(methoxy)methoxyphenylmagnesium bromide | 146746-34-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(methoxy)methoxyphenylmagnesium bromide
• 英文别名: 2-methoxymethoxyphenylmagnesium bromide
• CAS: 146746-34-1
• 化学式: C₈H₉BrMgO₂
• 分子量: 241.367
• InChiKey: TUVNDTVQEUHPPF-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.31
• 重原子数：
  12.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  18.46
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2-(methoxy)methoxyphenylmagnesium bromide 在 platinum(IV) oxide 、 palladium on activated charcoal 盐酸 、 三聚氯氰 、 氢气 、 1-羟基苯并三唑 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 氯仿 为溶剂， -40.0~25.0 ℃ 、3.0 MPa 条件下， 反应 8.0h， 生成 ethyl (2S,5R)-1-[2-[[(2S)-2-acetylsulfanyl-3-(4-methoxyphenyl)propanoyl]amino]acetyl]-5-(2-hydroxyphenyl)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Design of Orally Active Dual Inhibitors of Neutral Endopeptidase and Angiotensin-Converting Enzyme with Long Duration of Action

  摘要：

  Mercaptoacyl dipeptides, containing a glycine Linked to a C-terminal 5-phenylproline, have been synthesized in order to obtain new highly efficient dual inhibitors of the two zinc metallopeptidases, neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), which are involved in the control of blood pressure and fluid homeostasis. These compounds have been designed (i) to fit optimally the ACE pharmacophore previously described (Fournie-Zaluski, M. C.; et al. J. Med. Chem. 1994, 37, 1070-1083), through interaction with the S-1, S-1', and S-2' subsites of this enzyme, (ii) and to interact with the S-1' and S-2' subsites of NEP with the 5-phenylproline moiety outside the catalytic domain (Coric, P.; et al. J. Med. Chem. 1996, 39, 1210-1219). Replacement of Gly by Ala in these mercaptoacyl dipeptides induced an about 100-fold decreasein ACE inhibition. This shows that, in agreement with molecular modeling studies, a steric constraint as weak as a methyl group hinders optimal ACE active site recognition, Among these compounds, the dual inhibitor 26 (RB 106) (K-i, ACE =: 0.35 nM; NEP = 1.6 nM) showed excellent pharmacokinetic properties with an almost complete in vivo inhibition of NEP and ACE for more than 4 h after oral administration in mice of a low dose (2.6 x 10(-5) mol/kg) of the inhibitor. Moreover, RE 106 remained active 12 h after oral administration In spontaneous hypertensive rats, a chronic treatment of orally administered RB 106 (25 mg/kg/day) induced a prolonged hypotensive effect (-28 mmHg) still significant 2 days after the end of the treatment. In DOCA salt rats, a hypotensive response and a significant natriuresis were observed after iv administration RE 106, which is one of the most potent dual inhibitors described to date, could have interesting clinical applications in long term treatment of congestive heart failure and myocardial ischemia.

  DOI：

  10.1021/jm950783c
• 作为产物：
  描述：

  1-(甲氧基甲氧基)苯 在 正丁基锂 、 magnesium bromide 作用下， 生成 2-(methoxy)methoxyphenylmagnesium bromide
  参考文献：
  名称：

  An intramolecular arene-triflate coupling reaction for the regiospecific synthesis of substituted benzofluoranthenes

  摘要：

  An intramolecular triflate-arene coupling reaction mediated by bis(triphenylphosphine)palladium(II) chloride has been developed for the synthesis of each of the isomeric benzofluoranthenes. This reaction, which results in formation of a new five-membered ring, proceeds in highest yield when performed using 0.1 equiv of the palladium catalyst, 3 equiv of lithium chloride, and 1.2 equiv of 1,8-diazabicyclo[5.4.0]undec-7-ene in N,N-dimethylformamide at 140-degrees-C. The biaryl precursors needed for the coupling reaction can be prepared by [1,2-bis(diphenylphosphino)ethane]nickel(II) chloride catalyzed coupling of an aryl bromide with an [o-(methoxymethoxy)aryl]magnesium bromide (prepared by ortho-lithiation of an aryl methoxymethyl ether followed by transmetalation with magnesium bromide). Using this procedure benzo[a]fluoranthene, benzo[b]fluoranthene, benzo[j]fluoranthene, and benzo[k]fluoranthene were prepared in yields of 84%, 85%, 93%, and 64%, respectively. The reaction to prepare benzo[j]fluoranthene was regiospecific and afforded none of the six-membered ring product, perylene. The method was extended to the preparation of benzo[b]fluoranthene (BbF) derivatives with fluoro or methoxy groups on the benzo ring. The cyclization of compounds possessing a methoxy group on the same ring as the triflate required the addition of 0.4 equiv of triphenylphosphine to the reaction mixture. Strategies are reported for the regiospecific preparation of 4-, 5-, 6-, and 7-substituted benzo[b]fluoranthenes. Evidence is presented which suggests the intermediacy of radicals in the oxidative-addition of aryl triflates to the palladium catalyst.

  DOI：

  10.1021/jo00058a023
• 作为试剂：
  描述：

  methyl 2,3-anhydro-4,6-O-benzilidene-α-D-mannopyranoside 在 碲化氢 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 Amberlyst 15 (H+) resin 、 氯化铵 、 对甲苯磺酸 、 copper(II) sulfate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 2-(methoxy)methoxyphenylmagnesium bromide 、 barium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 乙二醇甲醚 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  3-氨基-5-C-苯基-D-呋喃喃糖和3-氨基-5-C- [3-羧基-4-（羧甲基）-2-氧代-3-环己烯-1-基] -D-呋喃喃糖，蒽环类抗生素去甲柔红霉素合成的可能中间体。

  摘要：

  DOI：

  10.1016/0008-6215(91)84152-5

文献信息

• Synthesis and antihypertensive activity of 5-(2-hydroxyphenyl)-1-(3-mercaptopropionyl)-2-pyrrolidinecarboxylic acids.
  作者：EISHIN KATO、KOJI YAMAMOTO、YOICHI KAWASHIMA、TOSHIO WATANABE、MASAYUKI OYA、TADASHI ISO、JUNICHI IWAO

  DOI：10.1248/cpb.33.4836

  日期：——

  The (2S, 5R)-(+)- or (2R, 5S)-(-)-thiol (4a or 4b) was synthesized by catalytic hydrogenation of the corresponding (S)-(-)- or (R)-(+)-pyrrolinecarboxylic acid (8a or 8b) resolved with (R)-(-)-1, 2-diphenylethylamine, followed by acylation with 3-(benzoylthio) propionyl chloride and ammonolysis. The thiols were converted into the corresponding O, S-diacetates (16a and 16b), which were transformed into (2R, 5R)-(+)- and (2S, 5S)-(-)-thiols (18a and 18b) via their O, S-diacetates (17a and 17b) by epimerization and then ammonolysis. The stereochemistry of these thiols was elucidated on the basis of synthesis from tert-butoxycarbonyl-L-glutamic acid γ-benzylester (9) and proton nuclear magnetic resonance (1H-NMR) analysis. The thiols were tested for inhibitory activity against angiotensin-converting enzyme in vitro. (2S, 5R)-5-(2-Hydroxyphenyl)-1-(3-mercaptopropionyl)-2-pyrrolidinecarboxylic acid (4a) showed the most potent activity among them.

  (2S, 5R)-(+)-或(2R, 5S)-(-)-硫醇（4a或4b）是通过催化氢化相应的(S)-(-)-或(R)-(+)-吡咯啉羧酸（8a或8b），该酸与(R)-(-)-1, 2-二苯基乙胺进行分离后合成的，随后进行酸酐化反应与3-(苯甲硫基)丙酰氯和氨解反应。将这些硫醇转化为相应的O,S-二乙酸酯（16a和16b），再通过其O,S-二乙酸酯（17a和17b）进行表异构化和氨解反应，转化为(2R, 5R)-(+)-和(2S, 5S)-(-)-硫醇（18a和18b）。这些硫醇的立体化学是在以叔丁氧羰基-L-谷氨酸γ-苄酯（9）为基础的合成和质子核磁共振（1H-NMR）分析的基础上阐明的。对这些硫醇进行了体外抗血管紧张素转化酶的抑制活性测试，其中(2S, 5R)-5-(2-羟基苯基)-1-(3-巯基丙酰)-2-吡咯烷羧酸（4a）显示出最强的活性。
• Highly Enantioselective Synthesis of Axially Chiral Biarylphosphonates: Asymmetric Suzuki-Miyaura Coupling Using High-Molecular-Weight, Helically Chiral Polyquinoxaline-Based Phosphines
  作者：Takeshi Yamamoto、Yuto Akai、Yuuya Nagata、Michinori Suginome

  DOI：10.1002/anie.201103792

  日期：2011.9.12

  Taking a new turn: An asymmetric Suzuki–Miyaura coupling of 1‐bromo‐2‐naphthalenephosphonic esters with o‐methyl‐substituted phenylboronic acids proceeds with high enantioselectivity in the presence of high‐molecular‐weight helically chiral polyquinoxaline‐based phosphines (PQXphos) bearing pendant diarylphosphino groups.

  发生新的变化：存在高分子量螺旋手性聚喹喔啉基膦（PQXphos）的情况下，1-溴-2-萘膦酸酯与邻甲基取代的苯基硼酸的不对称Suzuki-Miyaura偶联具有高对映选择性。带有二芳基膦基侧基。
• Enantioselective Claisen rearrangement of difluorovinyl allyl ethers
  作者：Hisanaka Ito、Azusa Sato、Tetsuo Kobayashi、Takeo Taguchi

  DOI：10.1039/a807157h

  日期：——

  The enantioselective Claisen rearrangement of difluorovinyl allyl ethers was achieved, for the first time, in moderate to good enantioselectivity using a chiral boron reagent as the Lewis acid.

  使用手性硼试剂作为路易斯酸，首次实现了二氟乙烯基烯丙基醚的对映体选择性克莱森重排，对映体选择性达到中等至良好水平。
• Non-C2-Symmetric, Chirally Economical, and Readily Tunable Linked-binols: Design and Application in a Direct Catalytic Asymmetric Mannich-Type Reaction
  作者：Takamasa Yoshida、Hiroyuki Morimoto、Naoya Kumagai、Shigeki Matsunaga、Masakatsu Shibasaki

  DOI：10.1002/anie.200500425

  日期：2005.5.30
• P-Chiral <i>o</i>-Phosphinophenol as a P/O Hybrid Ligand:  Preparation and Use in Cu-Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Acyclic Enones
  作者：Yukitoshi Takahashi、Yoshikazu Yamamoto、Kosuke Katagiri、Hiroshi Danjo、Kentaro Yamaguchi、Tsuneo Imamoto

  DOI：10.1021/jo051034y

  日期：2005.10.1

  (S)-2-(tert-Butylmethylphosphino)phenol and its methyl ether were synthesized from tert-butyldichlorophosphine via optically active phosphine-boranes as the intermediates. The former compound was used as a P/O hybrid ligand in the Cu-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones to achieve high enantioselectivity of up to 96%.