RC6Mhb5lyb | 1452167-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: RC6Mhb5lyb
• 英文别名: [(8R)-16-fluoro-18-oxa-6-azatetracyclo[9.7.0.02,7.012,17]octadeca-1(11),2(7),3,5,12(17),13,15-heptaen-8-yl]oxy-tri(propan-2-yl)silane
• CAS: 1452167-01-9
• 化学式: C₂₅H₃₂FNO₂Si
• 分子量: 425.618
• InChiKey: XQASROYRFJRZMJ-JOCHJYFZSA-N

物化性质

• 沸点：
  503.0±50.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.81
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  35.26
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (R)-9-((三异丙基硅基)氧基-6,7,8,9-四氢-5H-环庚基[B]吡啶-5-酮盐酸盐 在 potassium phosphate 、 palladium diacetate 、 sodium t-butanolate 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 2-甲基-2-丁醇 为溶剂， 反应 2.25h， 生成 RC6Mhb5lyb
  参考文献：
  名称：

  Development of a scalable palladium-catalyzed α-arylation process for the synthesis of a CGRP antagonist

  摘要：

  The Pd-catalyzed alpha-arylation of cycloheptapyridyl ketone is a key complexity-building step in the synthesis of BMS-846372, a CGRP antagonist. A first-generation process utilized Pd(OAc)(2)/(PBu3)-Bu-t center dot HBF4 catalyst system with a strong base (NaOBu)-Bu-t. Although this process was demonstrated on multi-kilo scale, the harsh conditions led to non-selective metal catalyzed processes, which generated several operational, quality, and throughput issues. By acquiring detailed knowledge around several important process parameters, we were able to design an efficient and scalable second-generation alpha-arylation process using a Pd(OAc)(2)/RuPhos catalyst system with the weaker base, K3PO4 in tert-amyl alcohol. This new weak base process was high yielding, efficient, and superior in several respects compared to the strong base process. The strategy behind the reaction and isolation development and the process considerations important to scaling a catalytic reaction from laboratory to manufacturing scale will be discussed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.04.057