(R)-α-hydroxy-α-<4-(2-fluoroethyl)phenyl>benzeneacetic acid | 153993-94-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-α-hydroxy-α-<4-(2-fluoroethyl)phenyl>benzeneacetic acid
• 英文别名: (R)-4-(2-fluoroethyl)benzilic acid；(R)-α-hydroxy-α-[4-(2-fluoroethyl)phenyl]benzeneacetic acid；(2R)-2-[4-(2-fluoroethyl)phenyl]-2-hydroxy-2-phenylacetic acid
• CAS: 153993-94-3
• 化学式: C₁₆H₁₅FO₃
• 分子量: 274.292
• InChiKey: SAGVCPVZQYOLJV-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-α-hydroxy-α-<4-(2-fluoroethyl)phenyl>benzeneacetic acid 、 (R)-(-)-3-奎宁醇 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以57%的产率得到(R,R)-FEtQNB
  参考文献：
  名称：

  Syntheses and Biological Properties of Chiral Fluoroalkyl Quinuclidinyl Benzilates

  摘要：

  Previously, (R)-quinuclidinyl (R)-4-iodobenzilate ((R,R)-IQNB), a muscarinic receptor antagonist, has been labeled with I-123 and I-125 for use in in vitro and in vivo studies in animals and humans. We have prepared fluoroalkyl analogs of QNB, which are amenable to labeling with F-18, for potential imaging applications with positron emission tomography. The enantiomers of (fluoroalkyl)benzilic acids were prepared via an enantioselective Grignard addition reaction. Subsequent coupling of the enantiomeric (fluoroalkyl)benzilic acid with a selected enantiomer of quinuclidinol provides fluorinated analogs of QNB with known stereochemistry at each of the stereogenic centers. These compounds exhibit different affinities for the muscarinic receptor tissue subtypes in vitro. (R,R)-4-(Fluoromethyl)-QNB, (R,R)-IQNB, and (R,R)-4-(fluoroethyl)-QNB exhibit selectivity for the M1 subtype, and (R,S)-4-(fluoromethyl)-QNB exhibits selectivity for the M2 subtype.

  DOI：

  10.1021/jm00010a016
• 作为产物：
  描述：

  4-溴苯乙醇 在 吡啶 、 氢氧化钾 、 sodium hydroxide 、 1,1-二氯甲醚 、 碘 、 magnesium 、 tetramethylammonium hydrogen difluoride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 13.17h， 生成 (R)-α-hydroxy-α-<4-(2-fluoroethyl)phenyl>benzeneacetic acid
  参考文献：
  名称：

  使用8-苯基薄荷醇作为手性助剂的苯甲酸类似物的不对称合成

  摘要：

  我们合成18 F-标记的毒蕈碱受体配体的程序需要制备手性氟烷基苯甲酸。使用8-苯基薄荷醇作为手性助剂，实现了对取代苯甲酸的对映选择性合成。在8-苯基薄荷基苯甲酰基甲酸酯7的si表面上进行格氏试剂以高选择性进行。手性诱导的结果支持先前通过结晶拆分的苯甲酸的手性分配。该方法用于合成（R）-奎宁环烷基-（R）-（4-碘）苯甲酸酯，事实证明与真实样品相同。另外，该方法允许以立体选择性的方式制备（R）-和（S）-氟乙基苯甲酸。

  DOI：

  10.1016/s0957-4166(00)80069-5

文献信息

• Asymmetric synthesis of benzilic acid analogues using 8-phenylmenthol as a chiral auxiliary
  作者：Dale O. Kiesewetter

  DOI：10.1016/s0957-4166(00)80069-5

  日期：1993.10

  ligands required the preparation of chiral fluoroalkyl benzilic acids. An enantioselective synthesis of substituted benzilic acids was achieved using 8-phenylmenthol as the chiral auxiliary. Grignard addition to the si face of 8-phenylmenthyl benzoylformate 7 proceeded with high selectivity. The results of the chiral induction support assignments of the chirality of benzilic acids previously resolved

  我们合成18 F-标记的毒蕈碱受体配体的程序需要制备手性氟烷基苯甲酸。使用8-苯基薄荷醇作为手性助剂，实现了对取代苯甲酸的对映选择性合成。在8-苯基薄荷基苯甲酰基甲酸酯7的si表面上进行格氏试剂以高选择性进行。手性诱导的结果支持先前通过结晶拆分的苯甲酸的手性分配。该方法用于合成（R）-奎宁环烷基-（R）-（4-碘）苯甲酸酯，事实证明与真实样品相同。另外，该方法允许以立体选择性的方式制备（R）-和（S）-氟乙基苯甲酸。
• Syntheses and Biological Properties of Chiral Fluoroalkyl Quinuclidinyl Benzilates
  作者：Dale O. Kiesewetter、James V. Silverton、William C. Eckelman

  DOI：10.1021/jm00010a016

  日期：1995.5

  Previously, (R)-quinuclidinyl (R)-4-iodobenzilate ((R,R)-IQNB), a muscarinic receptor antagonist, has been labeled with I-123 and I-125 for use in in vitro and in vivo studies in animals and humans. We have prepared fluoroalkyl analogs of QNB, which are amenable to labeling with F-18, for potential imaging applications with positron emission tomography. The enantiomers of (fluoroalkyl)benzilic acids were prepared via an enantioselective Grignard addition reaction. Subsequent coupling of the enantiomeric (fluoroalkyl)benzilic acid with a selected enantiomer of quinuclidinol provides fluorinated analogs of QNB with known stereochemistry at each of the stereogenic centers. These compounds exhibit different affinities for the muscarinic receptor tissue subtypes in vitro. (R,R)-4-(Fluoromethyl)-QNB, (R,R)-IQNB, and (R,R)-4-(fluoroethyl)-QNB exhibit selectivity for the M1 subtype, and (R,S)-4-(fluoromethyl)-QNB exhibits selectivity for the M2 subtype.