N-isopropylidene-D-phenylglycinol | 245443-16-7

• 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: N-isopropylidene-D-phenylglycinol
• 英文别名: (2R)-2-phenyl-2-(propan-2-ylideneamino)ethanol
• CAS: 245443-16-7
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: FSSSWTQKOQHXIL-NSHDSACASA-N

物化性质

• 沸点：
  277.0±33.0 °C(Predicted)
• 密度：
  0.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  32.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-isopropylidene-D-phenylglycinol 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以93%的产率得到(R)-2-异丙氨基-2-苯基乙醇
  参考文献：
  名称：

  Rational Design of Chiral Lithium Amides for Asymmetric Alkylation Reactions-NMR Spectroscopic Studies of Mixed Lithium Amide/Alkyllithium Complexes

  摘要：

  Treatment of solutions of chiral lithium amides, containing internally coordinating groups, in diethyl ether (DEE) with alkyllithiums results in the formation of chiral lithium amide/alkyl-lithium mixed dimers. We report the use of eight different chiral lithium amides/n-butyllithium mixed dimers in the asymmetric alkylation of benzaldehyde in DEE solution at -116 degrees C. The addition product, (S)-1-phenyl-1-pentanol, was formed with enantiomeric excesses (ee's) ranging from 0 to 82%. In DEE/dimethoxy methane solvent mixtures the stereoselectivity was improved and gave the product in 91% ee. Comparison of the ligand structures revealed that only one chiral center was necessary to obtain high enantioselectivity. Replacement of the internally coordinating methoxy group with a pyrrolidine group lowered the ee from 82% to 24%, Low-temperature Li-6 NMR studies of mixtures of these reagents in DEE revealed large differences in the concentration of the reactive mixed dimers formed. Full complexation of nBuLi to the chiral lithium amides is not necessary in order to obtain high enantioselectivity, as the result of an increased reactivity of the complexed nBuLi.

  DOI：

  10.1002/(sici)1521-3765(19990802)5:8<2348::aid-chem2348>3.0.co;2-a
• 作为产物：
  描述：

  D-苯甘氨醇 、 丙酮 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 72.0h， 以100%的产率得到N-isopropylidene-D-phenylglycinol
  参考文献：
  名称：

  Rational Design of Chiral Lithium Amides for Asymmetric Alkylation Reactions-NMR Spectroscopic Studies of Mixed Lithium Amide/Alkyllithium Complexes

  摘要：

  Treatment of solutions of chiral lithium amides, containing internally coordinating groups, in diethyl ether (DEE) with alkyllithiums results in the formation of chiral lithium amide/alkyl-lithium mixed dimers. We report the use of eight different chiral lithium amides/n-butyllithium mixed dimers in the asymmetric alkylation of benzaldehyde in DEE solution at -116 degrees C. The addition product, (S)-1-phenyl-1-pentanol, was formed with enantiomeric excesses (ee's) ranging from 0 to 82%. In DEE/dimethoxy methane solvent mixtures the stereoselectivity was improved and gave the product in 91% ee. Comparison of the ligand structures revealed that only one chiral center was necessary to obtain high enantioselectivity. Replacement of the internally coordinating methoxy group with a pyrrolidine group lowered the ee from 82% to 24%, Low-temperature Li-6 NMR studies of mixtures of these reagents in DEE revealed large differences in the concentration of the reactive mixed dimers formed. Full complexation of nBuLi to the chiral lithium amides is not necessary in order to obtain high enantioselectivity, as the result of an increased reactivity of the complexed nBuLi.

  DOI：

  10.1002/(sici)1521-3765(19990802)5:8<2348::aid-chem2348>3.0.co;2-a

文献信息

• PROCESS FOR PREPARING ELAGOLIX SODIUM AND INTERMEDIATES THEREOF
  申请人：ScinoPharm Taiwan, Ltd.

  公开号：US20210078956A1

  公开（公告）日：2021-03-18

  The present invention provides improved processes for the preparation of elagolix and intermediates thereof. The intermediate of formula VII is achieved by a coupling reaction of a compound of formula V and a N-benzylidene protected compound of formula IV: The present invention is suitable for a large-scale production, avoiding the use of potential genotoxic substances and can be performed under mild conditions.

  本发明提供了改进的制备elagolix及其中间体的方法。公式VII的中间体是通过公式V的化合物和公式IV的N-苯甲醛保护化合物的偶联反应实现的。本发明适用于大规模生产，避免使用潜在的致基因毒物质，并且可以在温和的条件下进行。
• Process for preparing elagolix sodium and intermediates thereof
  申请人：ScinoPharm Taiwan, Ltd.

  公开号：US11339131B2

  公开（公告）日：2022-05-24

  The present invention provides improved processes for the preparation of elagolix and intermediates thereof. The intermediate of formula VII is achieved by a coupling reaction of a compound of formula V and a N-benzylidene protected compound of formula IV: The present invention is suitable for a large-scale production, avoiding the use of potential genotoxic substances and can be performed under mild conditions.

  本发明提供了制备艾拉戈利及其中间体的改进工艺。式 VII 的中间体是通过式 V 的化合物和式 IV 的 N-亚苄基保护化合物的偶联反应实现的： 本发明适用于大规模生产，避免使用潜在的基因毒性物质，并可在温和的条件下进行。
• [EN] PROCESS FOR PREPARING ELAGOLIX SODIUM AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ÉLAGOLIX SODIQUE ET INTERMÉDIAIRES DE CELUI-CI
  申请人：SCINOPHARM TAIWAN LTD

  公开号：WO2021054896A1

  公开（公告）日：2021-03-25

  The present invention provides improved processes for the preparation of elagolix and intermediates thereof. The intermediate of formula VII is achieved by a coupling reaction of a compound of formula V and a N-benzylidene protected compound of formula IV: The present invention is suitable for a large-scale production, avoiding the use of potential genotoxic substances and can be performed under mild conditions.