(4-(benzyloxy)phenyl)hydroxyacetic acid ethyl ester | 109089-89-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4-(benzyloxy)phenyl)hydroxyacetic acid ethyl ester
• 英文别名: ethyl 2-(4-(benzyloxy)phenyl)-2-hydroxyacetate；4-Benzyloxy-mandelsaeure-aethylester；Et-4-benzyloxymandelat；4-benzyloxy-mandelic acid-ethyl ester；Ethyl 2-hydroxy-2-(4-phenylmethoxyphenyl)acetate
• CAS: 109089-89-6
• 化学式: C₁₇H₁₈O₄
• 分子量: 286.328
• InChiKey: CXJDDJYKMCBBJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-(benzyloxy)phenyl)hydroxyacetic acid ethyl ester 在 palladium on activated charcoal 五氯化磷 、 氢气 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 123.0h， 生成 7-<<4-(1-(allyloxycarbonyl)piperidin-4-yloxy)phenyl>(ethoxycarbonyl)methoxy>-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Tetrahydro-isoquinoline-Based Factor Xa Inhibitors

  摘要：

  Derivatives of (2-amidino-1,2,3,4-tetrahydro-isoquinolin-7-yloxy)phenylacetic acid (TIPAC) were developed as inhibitors of factor Xa (fXa). The compounds are prepared using 15 synthetic steps on average. The most potent compounds (14, 17, 22-26) display inhibition constants of K-i = 21-55 nM but do not inhibit thrombin (K-i = 5->100 mu M) and only weakly inhibit trypsin (K-i = 0.08-5 mu M). They bear a second basic moiety, e.g., substituted 1-(iminomethyl)piperidines, which is linked to C-4 of the phenyl group of TIPAC via an oxygen atom. The inhibition constants of these compounds are almost independent of the size of the (iminomethyl)piperidine substituent. Due to the fact that fXa displays two cation binding sites, namely, the S1 and S4 sites, in principle two binding modes are conceivable for the novel dibasic fXa inhibitors. Molecular modeling experiments based on the X-ray structures of uninhibited fXa and the DX-9065a/fXa complex were carried out. The results taken together with the inhibition constants clearly favor one binding mode: the tetrahydro-isoquinoline fills the S1 pocket even better than the naphthalene moiety of DX-9065a, and the (iminomethyl)piperidine residues occupy the S4 site.

  DOI：

  10.1021/jm9800402
• 作为产物：
  描述：

  3-(苄氧基苯基)乙酸乙酯 在 对甲苯磺酰叠氮 、 C₁₈BF₁₅*(x)H₂O 、 水 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 (4-(benzyloxy)phenyl)hydroxyacetic acid ethyl ester
  参考文献：
  名称：

  硼催化水中α-芳基α-重氮酸酯的OH键插入

  摘要：

  在存在B（C 6 F 5）3 · n H 2 O（2摩尔％）的条件下，开发了水中无催化的α-重氮酸酯插入金属的O–H键，从而获得了一系列的α-羟基酯。好到极好的产量。该反应具有易于操作和广泛的底物范围的特​​点，重要的是，与常规方法相比，不需要金属。重要的是，这种方法进一步扩展了B（C 6 F 5）3在耐水条件下的应用。

  DOI：

  10.1021/acs.orglett.8b01988

文献信息

• Sugiyama, Rikagaku Kenkyusho Iho, 1940, vol. 19, p. 802,803
  作者：Sugiyama

  DOI：——

  日期：——
• Boron-Catalyzed O–H Bond Insertion of α-Aryl α-Diazoesters in Water
  作者：Htet Htet San、Shi-Jun Wang、Min Jiang、Xiang-Ying Tang

  DOI：10.1021/acs.orglett.8b01988

  日期：2018.8.3

  A catalytic, metal-free O–H bond insertion of α-diazoesters in water in the presence of B(C6F5)3·nH2O (2 mol %) was developed, affording a series of α-hydroxyesters in good to excellent yields. The reaction features easy operation and wide substrate scope, and importantly, no metal is needed as compared with the conventional methods. Significantly, this approach further expands the applications of

  在存在B（C 6 F 5）3 · n H 2 O（2摩尔％）的条件下，开发了水中无催化的α-重氮酸酯插入金属的O–H键，从而获得了一系列的α-羟基酯。好到极好的产量。该反应具有易于操作和广泛的底物范围的特​​点，重要的是，与常规方法相比，不需要金属。重要的是，这种方法进一步扩展了B（C 6 F 5）3在耐水条件下的应用。
• Tetrahydro-isoquinoline-Based Factor Xa Inhibitors
  作者：Ralf Kucznierz、Frank Grams、Herbert Leinert、Klaus Marzenell、Richard A. Engh、Wolfgang von der Saal

  DOI：10.1021/jm9800402

  日期：1998.12.1

  Derivatives of (2-amidino-1,2,3,4-tetrahydro-isoquinolin-7-yloxy)phenylacetic acid (TIPAC) were developed as inhibitors of factor Xa (fXa). The compounds are prepared using 15 synthetic steps on average. The most potent compounds (14, 17, 22-26) display inhibition constants of K-i = 21-55 nM but do not inhibit thrombin (K-i = 5->100 mu M) and only weakly inhibit trypsin (K-i = 0.08-5 mu M). They bear a second basic moiety, e.g., substituted 1-(iminomethyl)piperidines, which is linked to C-4 of the phenyl group of TIPAC via an oxygen atom. The inhibition constants of these compounds are almost independent of the size of the (iminomethyl)piperidine substituent. Due to the fact that fXa displays two cation binding sites, namely, the S1 and S4 sites, in principle two binding modes are conceivable for the novel dibasic fXa inhibitors. Molecular modeling experiments based on the X-ray structures of uninhibited fXa and the DX-9065a/fXa complex were carried out. The results taken together with the inhibition constants clearly favor one binding mode: the tetrahydro-isoquinoline fills the S1 pocket even better than the naphthalene moiety of DX-9065a, and the (iminomethyl)piperidine residues occupy the S4 site.