methyl (+)-(3R,αR)-3-(N-benzyl-N-α-methylbenzylamino)hexanoate | 210294-87-4

• 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: methyl (+)-(3R,αR)-3-(N-benzyl-N-α-methylbenzylamino)hexanoate
• 英文别名: methyl (3R)-3-[benzyl-[(1R)-1-phenylethyl]amino]hexanoate
• CAS: 210294-87-4
• 化学式: C₂₂H₂₉NO₂
• 分子量: 339.478
• InChiKey: MZGIQMLJJYICHX-WIYYLYMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (+)-(3R,αR)-3-(N-benzyl-N-α-methylbenzylamino)hexanoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 10.0h， 生成 Methyl (3R)-3-aminohexanoate
  参考文献：
  名称：

  从对映体纯的β-氨基酯合成2,4,5-三取代的哌啶的一般方法。拟Distomin B三乙酸盐和拟Distomin F的全合成。

  摘要：

  对映纯β-氨基酯与丙烯酸甲酯的迈克尔加成反应，然后进行狄克曼缩合和烯醇甲硅烷基化，得到烯醇醚6，其通过阮内-镍在80atm和80℃下通过催化氢化而得到2,4,5-高非对映选择性的三取代哌啶。在这种情况下，Ni-H从2-烷基的方向攻击CC双键，以提供其中2,4,5-三取代的基团彼此都是顺式的产物。在没有N-Boc保护基的情况下氢化烯醇醚13得到产物15，其中4-羟基和5-酯部分反式为2-烷基。通过使用非对映选择性氢化产物9d和9e作为关键中间体，合成假乙酸二乙素B和乙酸假二素F。

  DOI：

  10.1021/jo000447q
• 作为产物：
  描述：

  反式-2-己烯甲酯 、 (R)-(+)-N-苄基-1-苯乙胺 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.25h， 以77%的产率得到methyl (+)-(3R,αR)-3-(N-benzyl-N-α-methylbenzylamino)hexanoate
  参考文献：
  名称：

  Asymmetric synthesis of 1,3-aminoketals

  摘要：

  The asymmetric synthesis of alpha-chiral 1,3-aminoketals 1, useful chiral building blocks for piperidine preparation, was achieved in seven steps involving highly diastereoselective 1,4-addition of Davies' lithium amide to an alpha,beta-unsaturated ester. Problems of partial racernization observed during transformation of the ester moiety into a keto function, via a Weinreb amide, were solved using non-conventional experimental conditions. This procedure allowed the preparation of the title compounds in > 90% enantiomeric excess. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2005.09.024

文献信息

• A One-Pot Formal [4 + 2] Cycloaddition Approach to Substituted Piperidines, Indolizidines, and Quinolizidines. Total Synthesis of Indolizidine (−)-209I
  作者：Shanghai Yu、Wei Zhu、Dawei Ma

  DOI：10.1021/jo051080y

  日期：2005.9.1

  delivers substituted piperidines in good yields. This transformation goes through a cascade Michael addition/alkylation process and represents a facile one-pot formal [4 + 2] cycloaddition approach to piperidine ring. Using secondary cyclic γ-chloropropylamines as substrates, this process produces substituted indolizidines or quinolizidines. On the basis of this approach, indolizidine (−)-209I is elaborated

  在70-83°C下加热i -PrOH中取代的N-苄基γ-氯丙胺，共轭炔酸或炔酮，碳酸钠和催化量的碘化钠的混合物，可得到高产率的取代哌啶。该转化经历级联的迈克尔加成/烷基化过程，代表对哌啶环的简便的一锅形式[4 + 2]环加成方法。使用仲环状γ-氯丙胺作为底物，该方法产生取代的吲哚并咪唑或喹唑烷。在此方法的基础上，由11个步骤从2-己酸甲酯精制了吲哚唑烷（-）-209I。
• Polyfunctionalized pyrrolidinones via the coupling of N,N-disubstituted β-amino esters with ethyl glyoxalate
  作者：Dawei Ma、Jiqing Jiang

  DOI：10.1016/s0957-4166(98)00016-0

  日期：1998.2

  N,N-Disubstituted amino esters were prepared by stereoselective conjugate addition of (S)- or (R)-lithium N-benzyl-N-α-methylbenzylamide to α,β-unsaturated esters. The couplings of the formed esters with ethyl glyoxalate followed by hydrogenation afforded 5-alkyl-4-carboethoxy-3-hydroxy-pyrrolidinones stereoselectively.

  通过将（S）-或（R）-锂N-苄基-N -α-甲基苄基酰胺立体选择性共轭加成到α，β-不饱和酯上来制备N，N-二取代的氨基酯。形成的酯与乙二醛乙酯的偶联，然后氢化，立体选择性地得到5-烷基-4-羰基乙氧基-3-羟基-吡咯烷酮。
• Diastereoselective synthesis of 2,4,5-trisubstituted piperidines from enantiopure β-amino esters
  作者：Dawei Ma、Haiying Sun

  DOI：10.1016/s0040-4039(99)00537-7

  日期：1999.4

  Reaction of (R)-beta-amino esters with methyl acrylate followed by Dieckmann condensation and enol silylation afforded the enol ethers 5, which were hydrogenated with catalysis by Raney-Ni to provide 2,4,5-trisubstituted piperidines with high diastereoselectivity. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Asymmetric synthesis of 1,3-aminoketals
  作者：Annabelle Bariau、Jean-Louis Canet、Pierre Chalard、Yves Troin

  DOI：10.1016/j.tetasy.2005.09.024

  日期：2005.11

  The asymmetric synthesis of alpha-chiral 1,3-aminoketals 1, useful chiral building blocks for piperidine preparation, was achieved in seven steps involving highly diastereoselective 1,4-addition of Davies' lithium amide to an alpha,beta-unsaturated ester. Problems of partial racernization observed during transformation of the ester moiety into a keto function, via a Weinreb amide, were solved using non-conventional experimental conditions. This procedure allowed the preparation of the title compounds in > 90% enantiomeric excess. (c) 2005 Elsevier Ltd. All rights reserved.
• General Route to 2,4,5-Trisubstituted Piperidines from Enantiopure β-Amino Esters. Total Synthesis of Pseudodistomin B Triacetate and Pseudodistomin F
  作者：Dawei Ma、Haiying Sun

  DOI：10.1021/jo000447q

  日期：2000.9.1

  The Michael addition reaction of enantiopure beta-amino esters with methyl acrylate followed by Dieckmann condensation and enol silylation affords the enol ethers 6, which are hydrogenated with catalysis by Raney-Ni at 80 atm and 80 degrees C to provide 2,4, 5-trisubstituted piperidines with high diastereoselectivity. In this case Ni-H attacks the C-C double bond from the direction of the 2-alkyl group

  对映纯β-氨基酯与丙烯酸甲酯的迈克尔加成反应，然后进行狄克曼缩合和烯醇甲硅烷基化，得到烯醇醚6，其通过阮内-镍在80atm和80℃下通过催化氢化而得到2,4,5-高非对映选择性的三取代哌啶。在这种情况下，Ni-H从2-烷基的方向攻击CC双键，以提供其中2,4,5-三取代的基团彼此都是顺式的产物。在没有N-Boc保护基的情况下氢化烯醇醚13得到产物15，其中4-羟基和5-酯部分反式为2-烷基。通过使用非对映选择性氢化产物9d和9e作为关键中间体，合成假乙酸二乙素B和乙酸假二素F。