(R)-methyl 2-((tert-butoxycarbonyl)amino)-2-(2-chlorophenyl)acetate | 1001414-68-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-methyl 2-((tert-butoxycarbonyl)amino)-2-(2-chlorophenyl)acetate
• 英文别名: N-Boc-(RS)-2-chlorophenylglycine methyl ester；methyl (2R)-2-(2-chlorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate
• CAS: 1001414-68-1
• 化学式: C₁₄H₁₈ClNO₄
• 分子量: 299.754
• InChiKey: LCOQLKXOKYSBQN-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 2-((tert-butoxycarbonyl)amino)-2-(2-chlorophenyl)acetate 在 protease from Bacillus licheniformis 作用下， 以 甲基叔丁基醚 为溶剂， 反应 65.0h， 以35%的产率得到(S)-N-Boc-(2’-氯苯基)甘氨酸
  参考文献：
  名称：

  Chemo-enzymatic approach to the synthesis of the antithrombotic clopidogrel

  摘要：

  The (S)-2-chlorophenylglycine moiety is well recognized in the structure of (S)-clopidogrel, a known antithrombotic drug. We prepared an enantiomerically pure chiral building block via an enzyme-catalyzed resolution of (RS)-N-Boc-2-chlorophenylglycine methylester. The best results were obtained by means of an immobilized subtilisin, the cross-linked enzyme aggregate (Alcalase-CLEA (R)). The high enantiomeric excess of the synthon obtained remained the same over the course of clopidogrel synthesis; the simplicity of the process makes this pathway suitable for large-scale preparation. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2010.06.040

文献信息

• Synthesis of α-Amino Acid Derivatives and Peptides via Enantioselective Addition of Masked Acyl Cyanides to Imines
  作者：Kin S. Yang、Viresh H. Rawal

  DOI：10.1021/ja510135t

  日期：2014.11.19

  asymmetric synthesis of amino acid derivatives is reported. Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective additions to N-Boc-aldimines. The reactions are catalyzed by a modified cinchona alkaloid, which can function as a bifunctional, hydrogen bonding catalyst, and afford adducts in excellent yields (90–98%) and high enantioselectivities (up to 97

  报告了氨基酸衍生物的一般不对称合成。掩蔽的酰基氰 (MAC) 试剂被证明是有效的 umpolung 合成子，用于对 N-Boc-醛亚胺进行对映选择性添加。该反应由改性的金鸡纳生物碱催化，该生物碱可用作双功能氢键催化剂，并以优异的产率（90-98%）和高对映选择性（高达 97.5:2.5 er）提供加合物。揭开加成产物得到酰基氰中间体，这些中间体被各种亲核试剂截获，得到 α-氨基酸衍生物。值得注意的是，该方法为肽键形成提供了一种替代方法。
• Asymmetric NH Insertion Reaction Cooperatively Catalyzed by Rhodium and Chiral Spiro Phosphoric Acids
  作者：Bin Xu、Shou-Fei Zhu、Xiu-Lan Xie、Jun-Jie Shen、Qi-Lin Zhou

  DOI：10.1002/anie.201105485

  日期：2011.11.25

  dirhodium(II) carboxylates and chiral spiro phosphoric acids (SPA) cooperatively catalyzed asymmetric NH insertion reactions with high enantioselectivity, high yields, and fast reaction rates at low catalyst loading (see scheme; Boc=tert‐butyloxycarbonyl, TPA=triphenylacetyl). Chiral spiro phosphoric acid assisted asymmetric proton transfer is proposed as the chiral induction step.

  所以附近以便SPA：非手性二铑（II）羧酸盐和手性螺环磷酸（SPA）协同催化的不对称N 在低催化剂负载高对映选择性，高收率，且快速反应速率ħ插入反应（参见方案将Boc =叔-丁氧羰基，TPA =三苯乙酰基）。手性螺线磷酸辅助不对称质子转移被认为是手性诱导步骤。
• WO2008/5457
  申请人：——

  公开号：——

  公开（公告）日：——
• Chemo-enzymatic approach to the synthesis of the antithrombotic clopidogrel
  作者：Patrizia Ferraboschi、Maria De Mieri、Fiorella Galimberti

  DOI：10.1016/j.tetasy.2010.06.040

  日期：2010.9

  The (S)-2-chlorophenylglycine moiety is well recognized in the structure of (S)-clopidogrel, a known antithrombotic drug. We prepared an enantiomerically pure chiral building block via an enzyme-catalyzed resolution of (RS)-N-Boc-2-chlorophenylglycine methylester. The best results were obtained by means of an immobilized subtilisin, the cross-linked enzyme aggregate (Alcalase-CLEA (R)). The high enantiomeric excess of the synthon obtained remained the same over the course of clopidogrel synthesis; the simplicity of the process makes this pathway suitable for large-scale preparation. (C) 2010 Elsevier Ltd. All rights reserved.