(3R,4R,5R)-ethyl 4,5-acetylimino-3-(pentan-3-yloxy)-cyclohex-1-enecarboxylate | 1268086-96-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: (3R,4R,5R)-ethyl 4,5-acetylimino-3-(pentan-3-yloxy)-cyclohex-1-enecarboxylate
• 英文别名: ethyl (1R,5R,6R)-7-acetyl-5-(pentan-3-yloxy)-7-azabicyclo[4.1.0]hept-3-ene-3-carboxylate；ethyl (3R,4R,5R)-4,5-acetylimino-3-(1-ethylpropoxy)cyclohex-1-ene-1-carboxylate；ethyl (1R,5R,6R)-7-acetyl-5-pentan-3-yloxy-7-azabicyclo[4.1.0]hept-3-ene-3-carboxylate
• CAS: 1268086-96-9
• 化学式: C₁₆H₂₅NO₄
• 分子量: 295.379
• InChiKey: JNJVGCIZOROHDS-BOEXNKMNSA-N

物化性质

• 沸点：
  420.1±45.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,4R,5R)-ethyl 4,5-acetylimino-3-(pentan-3-yloxy)-cyclohex-1-enecarboxylate 在 磷酸 、 三氟化硼乙醚 、 caesium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 2.95h， 生成 磷酸奥司他韦
  参考文献：
  名称：

  A novel azide-free asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from Roche’s epoxide

  摘要：

  A novel azide-free asymmetric synthesis of oseltamivir phosphate 1 (Tamiflu (R)) starting from Roche's epoxide is described. Roche epoxide 2 was converted into N-acetyl aminoalcohol 3 in 95% yield via a BF3 center dot OEt2-catalyzed epoxide-opening with acetonitrile as a nucleophile. Compound 3 was then transformed into a methanesulfonate 4 in 98% yield. Compound 4 was converted into aziridine 5 in 91% yield. Aziridine 5 was subsequently converted into oseltamivir phosphate 1 via two paths (a and b). In the path a, compound 5 underwent aziridine-opening with diallylamine as a nucleophile to afford compound 7 in 93% yield; compound 7 could then be converted into oseltamivir phosphate 1 in 88% yield. In path b, compound 5 underwent aziridine-opening with isopropyl 2,2,2-trichloroacetimidate as a nucleophile to afford compound 8 in 94% yield, which was then converted into oseltamivir phosphate 1 in 82% yield. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.04.016
• 作为产物：
  描述：

  ethyl (3S,4S,5S)-3,4-acetylimino-5-hydroxycyclohex-1-ene-1-carboxylate 在 4-二甲氨基吡啶 、 三氟化硼乙醚 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 3.5h， 生成 (3R,4R,5R)-ethyl 4,5-acetylimino-3-(pentan-3-yloxy)-cyclohex-1-enecarboxylate
  参考文献：
  名称：

  A novel and high-yielding asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from (−)-shikimic acid

  摘要：

  A novel and high-yielding asymmetric synthesis of oseltamivir phosphate 1 (Tamiflu(R)) is described. The target compound 1 was obtained in 55% overall yield via an 11-step asymmetric synthesis starting from the naturally abundant (-)-shikimic acid. The present synthesis is characterized by some advantages such as the easy separation of intermediate 6 from triphenylphosphine oxide by using its large water-solubility, the use of inexpensive reagents throughout the synthesis, the lack of toxic heavy metals, mild reaction conditions and high yields for all steps. The stereochemical structure of the key intermediate 6 was unequivocally confirmed by X-ray crystallographic analysis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.05.014

文献信息

• 一种奥司他韦乙酰氮丙啶中间体的制备方法
  申请人：华东理工大学

  公开号：CN108484467A

  公开（公告）日：2018-09-04

  本发明公开了一种奥司他韦(Oseltamivir)乙酰氮丙啶中间体I(附图1)的制备方法。该法以莽草酸环氧衍生物Ⅱ为原料，经六个化学合成步骤(附图2)制得奥司他韦乙酰氮丙啶中间体I，收率为44～61％。本发明包括以下六个化学合成步骤：(1)环氧化合物Ⅱ的3‑位开环并通过“一锅法”三步串联反应形成3,4‑位氮丙啶化合物Ⅲ；(2)3‑戊醇选择性进攻3‑位开环得到化合物Ⅳ；(3)4‑位脱除烯丙基得到化合物Ⅴ；(4)4‑位氨基乙酰化得化合物Ⅵ；(5)5‑位羟基甲磺酰化得到化合物Ⅶ；(6)4‑位乙酰氨基进攻5‑位关环得到奥司他韦乙酰氮丙啶中间体I。
• 一种奥司他韦的制备方法
  申请人：浙江工业大学

  公开号：CN114539088A

  公开（公告）日：2022-05-27

  本发明提供一种反应条件温和、操作简便、步骤少、成本低、收率高的奥司他韦的制备方法，该法以(1S，5R，6S)‑5‑(戊烷‑3‑基氧基)‑7‑氧杂双环[4.1.0]庚‑3‑羧酸乙酯为起始原料，经环氧开环、磺酰化、合环形成氮丙啶化合物，再经脱除保护基、乙酰化、氮丙啶开环，最后脱除保护基制得奥司他韦。
• CN116836075
  申请人：——

  公开号：——

  公开（公告）日：——
• A novel azide-free asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from Roche’s epoxide
  作者：Liang-Deng Nie、Fei-Feng Wang、Wei Ding、Xiao-Xin Shi、Xia Lu

  DOI：10.1016/j.tetasy.2013.04.016

  日期：2013.6

  A novel azide-free asymmetric synthesis of oseltamivir phosphate 1 (Tamiflu (R)) starting from Roche's epoxide is described. Roche epoxide 2 was converted into N-acetyl aminoalcohol 3 in 95% yield via a BF3 center dot OEt2-catalyzed epoxide-opening with acetonitrile as a nucleophile. Compound 3 was then transformed into a methanesulfonate 4 in 98% yield. Compound 4 was converted into aziridine 5 in 91% yield. Aziridine 5 was subsequently converted into oseltamivir phosphate 1 via two paths (a and b). In the path a, compound 5 underwent aziridine-opening with diallylamine as a nucleophile to afford compound 7 in 93% yield; compound 7 could then be converted into oseltamivir phosphate 1 in 88% yield. In path b, compound 5 underwent aziridine-opening with isopropyl 2,2,2-trichloroacetimidate as a nucleophile to afford compound 8 in 94% yield, which was then converted into oseltamivir phosphate 1 in 82% yield. (C) 2013 Elsevier Ltd. All rights reserved.
• A novel and high-yielding asymmetric synthesis of oseltamivir phosphate (Tamiflu) starting from (−)-shikimic acid
  作者：Liang-Deng Nie、Wei Ding、Xiao-Xin Shi、Na Quan、Xia Lu

  DOI：10.1016/j.tetasy.2012.05.014

  日期：2012.5

  A novel and high-yielding asymmetric synthesis of oseltamivir phosphate 1 (Tamiflu(R)) is described. The target compound 1 was obtained in 55% overall yield via an 11-step asymmetric synthesis starting from the naturally abundant (-)-shikimic acid. The present synthesis is characterized by some advantages such as the easy separation of intermediate 6 from triphenylphosphine oxide by using its large water-solubility, the use of inexpensive reagents throughout the synthesis, the lack of toxic heavy metals, mild reaction conditions and high yields for all steps. The stereochemical structure of the key intermediate 6 was unequivocally confirmed by X-ray crystallographic analysis. (C) 2012 Elsevier Ltd. All rights reserved.