ethyl 2-((tert-butoxycarbonyl)amino)-3,3-bis(4-fluorophenyl)acrylate | 1416247-60-3

• 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: ethyl 2-((tert-butoxycarbonyl)amino)-3,3-bis(4-fluorophenyl)acrylate
• 英文别名: Ethyl 3,3-bis(4-fluorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]prop-2-enoate
• CAS: 1416247-60-3
• 化学式: C₂₂H₂₃F₂NO₄
• 分子量: 403.426
• InChiKey: SKPGDPLLRSKTMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl 3,3-bis(4-fluorophenyl)-2-formamidoacrylate 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 ethyl 2-((tert-butoxycarbonyl)amino)-3,3-bis(4-fluorophenyl)acrylate
  参考文献：
  名称：

  （S）-N -Boc-双（4-氟苯基）丙氨酸的大规模合成

  摘要：

  从合成12 g原理样品到超过900 kg cGMP的生产过程，描述了（S）-N -Boc-双（4-氟苯基）丙氨酸的合成方法，该合成方法是合成denagliptin的中间体。通过空间拥挤的前体2-乙酰氨基-3,3-双（4-氟苯基）丙烯酸乙酯的不对称氢化来建立手性中心。以物理形式分离各种中间体的能力很容易进行过滤，洗涤和最终纯化，这为成功的制造活动奠定了基础。

  DOI：

  10.1021/op3002855

文献信息

• [EN] AN IMPROVED ASYMMETRIC SYNTHESIS OF alpha-(DIARYLMETHYL) ALKYL AMINES<br/>[FR] SYNTHÈSE ASYMÉTRIQUE AMÉLIORÉE D'ALPHA-(DIARYLMÉTHYL)ALKYLAMINES
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2019180627A1

  公开（公告）日：2019-09-26

  The present invention relates to an improved asymmetric synthesis of alpha- (diarylmethyl) alkyl amines (hereafter referred to as the compound (1)) or its pharmaceutically acceptable salt and derivatives. The process comprises an unusual substrate specific regioselective lithiation of alpha-diarylmethanes, followed by its highly diastereo selective addition to N-tert-butanesulfinylimines resulting in the selective formation of chiral alpha-(diarylmethyl) alkyl amines 4 and chiral amine 5; which on subsequently removing the sulfinyl group provides corresponding alpha-(diarylmethyl) alkyl amines (1) or relative chiral amines (1").

  本发明涉及一种改进的α-(二芳基甲基)烷基胺的不对称合成（以下简称为化合物（1））或其药用可接受的盐和衍生物。该过程包括对α-二芳基甲烷的不寻常底物特异性区域选择性锂化，然后将其高度对映选择性地加到N-叔丁基磺酰亚胺中，从而选择性地形成手性α-(二芳基甲基)烷基胺4和手性胺5；随后去除磺酰基可得到相应的α-(二芳基甲基)烷基胺（1）或相关手性胺（1"）。
• AN IMPROVED ASYMMETRIC SYNTHESIS OF ALPHA-(DIARYLMETHYL) ALKYL AMINES
  申请人：Piramal Pharma Limited

  公开号：EP3768659A1

  公开（公告）日：2021-01-27
• AN IMPROVED ASYMMETRIC SYNTHESIS OF alpha-(DIARYLMETHYL) ALKYL AMINES
  申请人：PIRAMAL ENTERPRISES LIMITED

  公开号：US20210061752A1

  公开（公告）日：2021-03-04

  The present invention relates to an improved asymmetric synthesis of alpha-(diarylmethyl) alkyl amines (hereafter referred to as the compound (1)) or its pharmaceutically acceptable salt and derivatives. The process comprises an unusual substrate specific regioselective lithiation of alpha-diarylmethanes, followed by its highly diastereoselective addition to N-tert-butanesulfinylimines resulting in the selective formation of chiral alpha-(diarylmethyl) alkyl amines 4 and chiral amine 5; which on subsequently removing the sulfinyl group provides corresponding alpha-(diarylmethyl) alkyl amines (1) or relative chiral amines (1″).