ethyl (R)-3-hydrazinyl-2,5-dioxopyrrolidine-3-carboxylate hydrochloride | 952656-32-5

• 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 (R)-3-hydrazinyl-2,5-dioxopyrrolidine-3-carboxylate hydrochloride
• 英文别名: R-(-)-3-ethoxycarbonyl-3-hydrozinopyrrolidin-2,5-dione hydrochloride
• CAS: 952656-32-5
• 化学式: C₇H₁₁N₃O₄*ClH
• 分子量: 237.643
• InChiKey: HMMBSSSLQPQFEK-OGFXRTJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.78
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  110.52
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl (R)-3-hydrazinyl-2,5-dioxopyrrolidine-3-carboxylate hydrochloride 在 镍 水 、 氢气 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 69.0h， 生成 雷尼司他
  参考文献：
  名称：

  实现 AS-3201 的高效催化不对称合成

  摘要：

  描述了通过催化不对称胺化与新型镧-酰胺复合物催化不对称合成 AS-3201。胺化反应在低至 1 mol% 的催化剂负载下有效进行，从而可以有效地获得合成 ​​AS-3201（一种有效的醛糖还原酶抑制剂）的关键中间体。

  DOI：

  10.1021/ja0752585
• 作为产物：
  描述：

  R-(-)-3-ethoxycarbonyl-3-(N,N'-di(tert-butoxycarbonyl)hydrazino)pyrrolidin-2,5-dione 在 盐酸 作用下， 以 乙酸乙酯 、 异丙醇 为溶剂， 反应 13.0h， 以2.66 kg的产率得到ethyl (R)-3-hydrazinyl-2,5-dioxopyrrolidine-3-carboxylate hydrochloride
  参考文献：
  名称：

  镧催化的不对称胺在公斤级规模的合成中首次用于手性琥珀酰亚胺衍生物的合成，该中间体是制备AS-3201的关键中间体

  摘要：

  描述了用于制造AS-3201（1）的手性中间体-（R）-3-氨基-2,5-二氧杂吡咯烷-3-羧酸乙酯（2）的工艺开发。开发并生成了一种实用且可扩展的Shibasaki不对称胺基化物，该胺基化物可生成手性四元中心。还开发了肼中间体的安全，方便和大规模氢化。

  DOI：

  10.1021/acs.oprd.6b00053

文献信息

• Managing Highly Coordinative Substrates in Asymmetric Catalysis: A Catalytic Asymmetric Amination with a Lanthanum-Based Ternary Catalyst
  作者：Tomoyuki Mashiko、Naoya Kumagai、Masakatsu Shibasaki

  DOI：10.1021/ja9052653

  日期：2009.10.21

  Full details of a catalytic asymmetric amination with a lanthanum/amide-based ligand catalyst system are described. A catalyst comprising La(NO3)(3)center dot 6H(2)O, (R)-3a and H-D-Val-V'Bu was identified to promote the catalytic asymmetric amination of nonprotected succinimide derivative 1 with as little as 1 mol % catalyst loading Mechanistic studies by various spectroscopic analyses and several control and kinetic experiments suggested that the catalyst components were in equilibrium between the associated and dissociated forms, and that the reaction likely proceeded through a La(NO3)(3)center dot 6H(2)O/(R)-3a/H-D-Val-O'Bu ternary complex. This catalyst system was also effective for asymmetric amination of N-nonsubstituted alpha-alkoxycarbonyl amides 7, hitherto unprecedented substrates in asymmetric catalysis, probably due to their attenuated reactivity and difficult stereocontrol, affording the amination products in up to > 99% yield and > 99% ee. The high catalytic performance and enantiocontrol of the reaction with highly coordinative substrates were achieved by the activation/recognition of the substrates exerted by coordination to lanthanum and hydrogen bonding cooperatively in the transition state.
• An Improved Lanthanum Catalyst System for Asymmetric Amination: Toward a Practical Asymmetric Synthesis of AS-3201 (Ranirestat)
  作者：Tomoyuki Mashiko、Naoya Kumagai、Masakatsu Shibasaki

  DOI：10.1021/ol8008446

  日期：2008.7.3

  A catalytic asymmetric amination with a lanthanum/amide complex was significantly improved. The use of lanthanum nitrate hydrate in place of lanthanum triisopropoxide made the process reproducible, scalable, and cost-effective. The development of a ternary catalytic system of La/ligand/amine was a key to high ee and catalytic turnover. A 100 g scale reaction was performed to showcase a practical synthesis of a key intermediate for AS-3201, a highly potent aldose reductase inhibitor.