(S)-5-sec-butyl-4-(4-methoxybenzyl)morpholin-3-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-5-sec-butyl-4-(4-methoxybenzyl)morpholin-3-one
• 英文别名: (5S)-5-sec-butyl-4-p-methoxybenzylmorpholin-3-one；(5S)-5-butan-2-yl-4-[(4-methoxyphenyl)methyl]morpholin-3-one
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: CLTVLQHJOLRCCL-WPZCJLIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-5-sec-butyl-4-(4-methoxybenzyl)morpholin-3-one 在 palladium on activated charcoal ammonium cerium(IV) nitrate 、 氢气 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -78.0~150.0 ℃ 、137.9 kPa 条件下， 反应 16.83h， 生成 (2R,5S)-2-benzyl-5-sec-butylmorpholin-3-one
  参考文献：
  名称：

  Alkylation Studies of N-Protected-5-substituted Morpholin-3-ones. A Stereoselective Approach to Novel Methylene Ether Dipeptide Isosteres

  摘要：

  We have developed a versatile new synthesis of the Psi[CH2O] pseudopeptides from N-protected-5-substituted morpholin-3-ones. The morpholin-3-ones are prepared in two steps from the corresponding amino alcohols by treatment with ethyl chloroacetate, followed by protection of the amide, We found that direct alkylation of the protected morpholin-3-ones gives the expected alkylation product where the electrophile approaches from the face opposite to the existing side chain (derived from the amino alcohol). If an S amino alcohol is used, this procedure results in the formation of the (SE) Psi[CH2O] dipeptide. Alternatively, the (S,S) Psi[CH2O] dipeptide can be obtained if the protected morpholin-3-one enolate is quenched with an aldehyde and the aldol product is dehydrated and reduced. We have explored an alkylation/deprotonation/kinetic protonation scheme which is also amenable to the preparation of (S,S) pseudodipetides. It is, of course, possible to obtain the corresponding (R,R) and (S,R) Psi[CH2O] dipeptides by simply selecting the appropriate amino alcohols and reaction conditions. Finally, we have established that this method is general and can be applied to the preparation of numerous Psi[CH2O] dipeptides which were previously unavailable by existing methods.

  DOI：

  10.1021/jo960496w
• 作为产物：
  描述：

  (2S)-2-amino-3-methyl-1-pentanol 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 paraffin 为溶剂， 反应 8.5h， 生成 (S)-5-sec-butyl-4-(4-methoxybenzyl)morpholin-3-one
  参考文献：
  名称：

  Alkylation Studies of N-Protected-5-substituted Morpholin-3-ones. A Stereoselective Approach to Novel Methylene Ether Dipeptide Isosteres

  摘要：

  We have developed a versatile new synthesis of the Psi[CH2O] pseudopeptides from N-protected-5-substituted morpholin-3-ones. The morpholin-3-ones are prepared in two steps from the corresponding amino alcohols by treatment with ethyl chloroacetate, followed by protection of the amide, We found that direct alkylation of the protected morpholin-3-ones gives the expected alkylation product where the electrophile approaches from the face opposite to the existing side chain (derived from the amino alcohol). If an S amino alcohol is used, this procedure results in the formation of the (SE) Psi[CH2O] dipeptide. Alternatively, the (S,S) Psi[CH2O] dipeptide can be obtained if the protected morpholin-3-one enolate is quenched with an aldehyde and the aldol product is dehydrated and reduced. We have explored an alkylation/deprotonation/kinetic protonation scheme which is also amenable to the preparation of (S,S) pseudodipetides. It is, of course, possible to obtain the corresponding (R,R) and (S,R) Psi[CH2O] dipeptides by simply selecting the appropriate amino alcohols and reaction conditions. Finally, we have established that this method is general and can be applied to the preparation of numerous Psi[CH2O] dipeptides which were previously unavailable by existing methods.

  DOI：

  10.1021/jo960496w

文献信息

• Stereoselective synthesis of novel methylene ether dipeptide isosteres
  作者：Bryan H. Norman、Julian S. Kroin

  DOI：10.1016/0040-4039(95)00712-l

  日期：1995.6

  We have developed a versatile new synthesis of the Ψ[CH2O] pseudopeptides from N-protected 5-substituted morpholin-3-ones. This approach focuses on a stereoselective alkylation of the morpholin-3-ones. The resulting alkylation products were used in the synthesis of some previously unavailable Ψ[CH2O] dipeptides.

  我们已经开发了一种由N保护的5-取代的吗啉-3-酮合成Ψ[CH 2 O]假肽的通用新方法。该方法集中于吗啉-3-酮的立体选择性烷基化。所得的烷基化产物用于合成某些先前无法获得的Ψ[CH 2 O]二肽。