N-[N'-tosyl-(2S)-propyl]-(3R)-2,3-dihydro-3-methyl-4H-1,4-benzoxazine | 602297-58-5

• 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-[N'-tosyl-(2S)-propyl]-(3R)-2,3-dihydro-3-methyl-4H-1,4-benzoxazine
• 英文别名: (3R,2'S)-3-methyl-N-(N'-tosylprolyl)-3,4-dihydro-2H-[1,4]benzoxazine；[(3R)-3-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[(2S)-1-(4-methylphenyl)sulfonylpyrrolidin-2-yl]methanone
• CAS: 602297-58-5
• 化学式: C₂₁H₂₄N₂O₄S
• 分子量: 400.499
• InChiKey: BLDUBDIOCHHVBU-APWZRJJASA-N

物化性质

• 熔点：
  158-160 °C(Solv: hexane (110-54-3); ethyl acetate (141-78-6))
• 沸点：
  622.4±65.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[N'-tosyl-(2S)-propyl]-(3R)-2,3-dihydro-3-methyl-4H-1,4-benzoxazine 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 40.0h， 以78%的产率得到(R)-3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine
  参考文献：
  名称：

  Kinetic resolution of (±)-2,3-dihydro-3-methyl-4H-1,4-benzoxazine, (±)-2-methyl-1,2,3,4-tetrahydroquinoline and (±)-2-methylindoline using N-tosyl-(S)-prolyl chloride

  摘要：

  Acylation of racemic 2,3-dihydro-3-methyl-4H-1,4-benzoxazine, 2-methyl-1,2,3,4-tetrahydroquinoline and 2-methylindoline with N-tosyl-(S)-prolyl chloride resulted in their kinetic resolution with the predominant formation of (R,S)-diastereoisomeric amides. des being 80, 66 and 38%, respectively. Recrystallisation of the amides followed by acid hydrolysis gave individual (R)-enantiomers of heterocyclic amines. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(03)00321-5
• 作为产物：
  描述：

  1-(甲苯-4-磺酰基)-吡咯烷-2-羧酸 在 草酰氯 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 12.0h， 生成 N-[N'-tosyl-(2S)-propyl]-(3R)-2,3-dihydro-3-methyl-4H-1,4-benzoxazine
  参考文献：
  名称：

  N-甲苯磺酰基-（S）-脯氨酰氯化物在外消旋杂环胺的动力学拆分中的应用

  摘要：

  系统研究了外消旋杂环胺经N-甲苯磺酰基-（S）-脯氨酰氯酰化的动力学拆分。已经确定，芳族胺的外消旋混合物可以高效分离，而2-和3-甲基哌啶的酰化则以低的非对映选择性发生。开发了制备对映体纯的（3 R）-7,8-二氟-3-甲基-3,4-二氢-2 H- [1,4]苯并恶嗪的方法。

  DOI：

  10.1007/s10593-014-1432-4

文献信息

• Diastereoselective Acylation of Racemic Heterocyclic Amines with N-Tosyl-(S)-Prolyl Chloride and its Structural Analogs
  作者：S. A. Vakarov、D. A. Gruzdev、E. N. Chulakov、L. Sh. Sadretdinova、M. A. Ezhikova、M. I. Kodess、G. L. Levit、V. P. Krasnov

  DOI：10.1007/s10593-014-1538-8

  日期：2014.9

  resolution of racemic amines (2,3-dihydro-4H-1,4-benzoxazine and 1,2,3,4-tetrahydroquinoline derivatives) via diastereoselective acylation with N-tosyl-(S)-prolyl chloride and its structural analogs was performed. The effect of resolving agent structure on the stereoselectivity of heterocyclic amine acylation was examined. The highest stereoselectivity was achieved in the case of acylation with acyl chlorides

  通过N-甲苯磺酰基-（S）-脯氨酰氯的非对映选择性酰化反应得到外消旋胺（2,3-二氢-4H-1,4-苯并恶嗪和1,2,3,4-四氢喹啉衍生物）的动力学拆分的比较研究并进行了结构类似物。考察了拆分剂结构对杂环胺酰化立体选择性的影响。在用带有构象受限的吡咯烷环和在氮原子上的保护基团上的芳族取代基的酰氯酰化的情况下，可获得最高的立体选择性。
• Kinetic resolution of heterocyclic amines by reaction with optically active acid chlorides. The effect of reaction conditions on the diastereoselectivity of acylation of (±)-3-methyl-2,3-dihydro-4H-1,4-benzoxazine
  作者：V. P. Krasnov、G. L. Levit、M. A. Korolyova、I. M. Bukrina、L. Sh. Sadretdinova、I. N. Andreeva、V. N. Charushin、O. N. Chupakhin

  DOI：10.1023/b:rucb.0000042282.29765.2f

  日期：2004.6

  of the reaction conditions (solvent, base) on the diastereoselectivity of acylation of (±)-3-methyl-2,3-dihydro-4H-1,4-benzoxazine with (S)-naproxen and N-tosyl-(S)-proline chlorides was studied. The highest diastereoselectivity was observed for the reaction carried out in benzene in the presence of aliphatic tertiary amines.

  反应条件（溶剂、碱）对(±)-3-甲基-2,3-二氢-4H-1,4-苯并恶嗪与(S)-萘普生和N-甲苯磺酰基-(研究了 S)-脯氨酸氯化物。在脂肪族叔胺存在下在苯中进行的反应观察到最高的非对映选择性。
• N-Tosyl-(S)-Prolyl Chloride in Kinetic Resolution of Racemic Heterocyclic Amines
  作者：D. A. Gruzdev、S. A. Vakarov、G. L. Levit、V. P. Krasnov

  DOI：10.1007/s10593-014-1432-4

  日期：2014.3

  The kinetic resolution of racemic heterocyclic amines via acylation with N-tosyl-(S)-prolyl chloride was systematically investigated. It was established that racemic mixtures of aromatic amines could be resolved with high efficiency, while the acylation of 2- and 3-methylpiperidines occurred with low diastereoselectivity. A method for the preparation of enantiomerically pure (3R)-7,8-difluoro-3-methyl-3

  系统研究了外消旋杂环胺经N-甲苯磺酰基-（S）-脯氨酰氯酰化的动力学拆分。已经确定，芳族胺的外消旋混合物可以高效分离，而2-和3-甲基哌啶的酰化则以低的非对映选择性发生。开发了制备对映体纯的（3 R）-7,8-二氟-3-甲基-3,4-二氢-2 H- [1,4]苯并恶嗪的方法。
• Kinetic resolution of (±)-2,3-dihydro-3-methyl-4H-1,4-benzoxazine, (±)-2-methyl-1,2,3,4-tetrahydroquinoline and (±)-2-methylindoline using N-tosyl-(S)-prolyl chloride
  作者：Victor P. Krasnov、Galina L. Levit、Iraida M. Bukrina、Irina N. Andreeva、Liliya Sh. Sadretdinova、Marina A. Korolyova、Mikhail I. Kodess、Valery N. Charushin、Oleg N. Chupakhin

  DOI：10.1016/s0957-4166(03)00321-5

  日期：2003.7

  Acylation of racemic 2,3-dihydro-3-methyl-4H-1,4-benzoxazine, 2-methyl-1,2,3,4-tetrahydroquinoline and 2-methylindoline with N-tosyl-(S)-prolyl chloride resulted in their kinetic resolution with the predominant formation of (R,S)-diastereoisomeric amides. des being 80, 66 and 38%, respectively. Recrystallisation of the amides followed by acid hydrolysis gave individual (R)-enantiomers of heterocyclic amines. (C) 2003 Elsevier Science Ltd. All rights reserved.