2-benzyloxycarbonyl-1-tert-butoxycarbonyl-2-methoxycarbonylmethylhydrazine | 200813-56-5

• 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: 2-benzyloxycarbonyl-1-tert-butoxycarbonyl-2-methoxycarbonylmethylhydrazine
• 英文别名: Methyl 2-[[(2-methylpropan-2-yl)oxycarbonylamino]-phenylmethoxycarbonylamino]acetate
• CAS: 200813-56-5
• 化学式: C₁₆H₂₂N₂O₆
• 分子量: 338.36
• InChiKey: SPBCBRIKIKJSOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-benzyloxycarbonyl-1-tert-butoxycarbonyl-2-methoxycarbonylmethylhydrazine 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以98%的产率得到2-[[(2-Methylpropan-2-yl)oxycarbonylamino]-phenylmethoxycarbonylamino]acetic acid
  参考文献：
  名称：

  Synthesis of Nα-Z, Nβ-Fmoc or Boc protected α-hydrazinoacids and study of the coupling reaction in solution of Nα-Z-α-hydrazinoesters

  摘要：

  The preparation of chiral orthogonally protected N-alpha-Z, N-beta-Fmoc- or Boc-alpha-hydrazinoacids derivatives, directly suitable for SPPS, is described in six steps with good yields starting from the corresponding alpha-aminoacids. The coupling reaction assays performed in liquid phase between N-alpha-Z-hydrazinoesters and N-Fmoc-alpha-aminoacids demonstrated the low reactivity of the hydrazinoester derivatives. However, we found that the acid fluoride method allowed the formation of hydrazinodipeptides almost quantitatively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.12.085
• 作为产物：
  描述：

  N-(苄氧羰基-氨基)邻苯二甲酰亚胺 在 4-二甲氨基吡啶 、 dialkylazodicarboxylate 、 三苯基膦 、 甲胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 12.5h， 生成 2-benzyloxycarbonyl-1-tert-butoxycarbonyl-2-methoxycarbonylmethylhydrazine
  参考文献：
  名称：

  Synthesis of Nα-Z, Nβ-Fmoc or Boc protected α-hydrazinoacids and study of the coupling reaction in solution of Nα-Z-α-hydrazinoesters

  摘要：

  The preparation of chiral orthogonally protected N-alpha-Z, N-beta-Fmoc- or Boc-alpha-hydrazinoacids derivatives, directly suitable for SPPS, is described in six steps with good yields starting from the corresponding alpha-aminoacids. The coupling reaction assays performed in liquid phase between N-alpha-Z-hydrazinoesters and N-Fmoc-alpha-aminoacids demonstrated the low reactivity of the hydrazinoester derivatives. However, we found that the acid fluoride method allowed the formation of hydrazinodipeptides almost quantitatively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.12.085

文献信息

• Liquid and solid phase syntheses of orthogonally protected α-hydrazinoacid derivatives
  作者：Isabelle Bouillon、Nicolas Brosse、Régis Vanderesse、Brigitte Jamart-Grégoire

  DOI：10.1016/j.tetlet.2004.03.063

  日期：2004.4

  phase, result in efficient releases of orthogonally bis-protected or fully tris-protected hydrazine derivatives. A comparison between liquid and solid phase syntheses is outlined: even if the overall yields are sometimes rather higher by the liquid phase synthesis, the on-resin protocol is much more rapid and convenient than the liquid protocol.

  已经开发了手性α-肼基酸的第一固相合成。该合成通过制备在涉及α-羟基酯的Mitsunobu方案中用作酸性伙伴的固体负载的N-烷氧基羰基-氨基邻苯二甲酰亚胺来实现。首先在液相中进行的邻苯二甲酰基的两个不同的最终反保护步骤导致正交双保护或完全三保护的肼衍生物的有效释放。概述了液相和固相合成之间的比较：即使通过液相合成有时总产率有时会更高，但树脂上的操作方案比液相操作要快得多且方便得多。
• A Practical Reagent for the Synthesis of Substituted Hydrazines
  作者：Leif Grehn、Berthelemy Nyasse、Ulf Ragnarsson

  DOI：10.1055/s-1997-1368

  日期：1997.12

  A practical, inexpensive triprotected hydrazine reagent, 2-benzyl-oxycarbonyl-1-tert-butoxycarbonyl-1-(4-methylphenylsulfonyl)-hydrazine, 1-Boc-1-Tos-2-Z-hydrazine (2), has been prepared on a 100 mmol scale and examined with respect to application in stepwise synthesis of unsymmetrically substituted hydrazines. The use of three protective groups excludes undesired substitution on the nitrogens even under forcing conditions. The initial alkylation which can be accomplished quantitatively is followed by the removal of the tosyl moiety. Due to the presence of a Boc group on the sulfonamide nitrogen atom, the otherwise rather stable sulfonamide function can be cleanly and efficiently cleaved reductively by magnesium in dry methanol to provide a second alkylation site. Such intermediates have recently been converted to tetrasubstituted hydrazines. With sonication this reduction is generally complete within 30 minutes. The new reagent exhibits increased stability to base in comparison with its predecessor and is more suitable and economical for work on a larger scale.

  一种实用、廉价的三保护肼试剂--2-苄基-氧羰基-1-叔丁氧羰基-1-（4-甲基苯磺酰基）肼，1-Boc-1-Tos-2-Z-肼 (2) 以 100 毫摩尔的规模制备出来，并对其在逐步合成不对称取代的肼中的应用进行了研究。即使在强制条件下，使用三个保护基团也能避免硝基发生不希望发生的取代。最初的烷基化可以定量完成，然后去除甲苯基。由于磺酰胺氮原子上存在一个叔丁氧羰基，镁在干燥甲醇中可还原性地裂解原本相当稳定的磺酰胺官能团，从而提供第二个烷基化位点。这种中间体最近被转化为四取代肼。通过超声处理，这种还原反应一般可在 30 分钟内完成。与前一种试剂相比，新试剂对碱的稳定性有所提高，更适合大规模生产，也更经济。
• Synthesis of Nα-Z, Nβ-Fmoc or Boc protected α-hydrazinoacids and study of the coupling reaction in solution of Nα-Z-α-hydrazinoesters
  作者：Isabelle Bouillon、Nicolas Brosse、Régis Vanderesse、Brigitte Jamart-Grégoire

  DOI：10.1016/j.tet.2006.12.085

  日期：2007.3

  The preparation of chiral orthogonally protected N-alpha-Z, N-beta-Fmoc- or Boc-alpha-hydrazinoacids derivatives, directly suitable for SPPS, is described in six steps with good yields starting from the corresponding alpha-aminoacids. The coupling reaction assays performed in liquid phase between N-alpha-Z-hydrazinoesters and N-Fmoc-alpha-aminoacids demonstrated the low reactivity of the hydrazinoester derivatives. However, we found that the acid fluoride method allowed the formation of hydrazinodipeptides almost quantitatively. (c) 2007 Elsevier Ltd. All rights reserved.