(1S,2R)-1-phenyl-2-acetyl-N,N-diethylcyclopropanecarboxamide | 171889-17-1

• 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: (1S,2R)-1-phenyl-2-acetyl-N,N-diethylcyclopropanecarboxamide
• 英文别名: (1S,2R)-2-acetyl-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
• CAS: 171889-17-1
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: WBLGALSJKLTXAQ-GOEBONIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,2R)-1-phenyl-2-acetyl-N,N-diethylcyclopropanecarboxamide 在 氢气 作用下， 生成 (1S,2R)-1-phenyl-2-<(R)-1-hydroxyethyl>-N,N-diethylcyclopropanecarboxamide
  参考文献：
  名称：

  （+）-和（-）-米那普仑及其构象受限的类似物的合成

  摘要：

  （R）-表氯醇[（R）-5 ]与苯乙腈（6）在NaNH 2的存在下在苯中的反应生成环丙烷衍生物，其被分离为内酯4 [（1 S，2 R）-2-氧-在氰基进行碱性水解后，96％ee的1-苯基-3-氧杂双环[3,1,0]己烷]的收率为67％。化合物4容易地转化为（+）-米那普仑[（+）- 1 ]，由此证实了（+）- 1的绝对立体化学。（1 S，2 R）-1-苯基-2-[（（S）-1-氨乙基]-环丙烷-N，N-diethylcarboxamindes（2），构象受限的1的类似物，还从4合成高对映体纯度。从（S）-表氯醇[（S）-5 ]开始，还合成了它们相应的对映异构体，即（-）-米那普仑[（-）- 1 ]和ent-2 。

  DOI：

  10.1016/0040-4039(95)02221-x
• 作为产物：
  描述：

  (1S,2R)-2-Formyl-1-phenyl-cyclopropanecarboxylic acid diethylamide 在 重铬酸吡啶 、 4 A molecular sieve 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (1S,2R)-1-phenyl-2-acetyl-N,N-diethylcyclopropanecarboxamide
  参考文献：
  名称：

  Conformational Restriction by Repulsion between Adjacent Substituents on a Cyclopropane Ring:  Design and Enantioselective Synthesis of 1-Phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides as Potent NMDA Receptor Antagonists

  摘要：

  Adjacent substituents on a cyclopropane ring mutually exert steric repulsion quite significantly, because they are fixed in eclipsed conformation to each other. Based on this structural feature of the cyclopropane ring, conformationally restricted analogs of milnacipran (1), namely 1-phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides (2, 3, ent-2, and ent-3) were designed as potent NMDA receptor antagonists and were synthesized highly enantioselectively. Reaction of (R)epichlorohydrin [(R)-5] and phenylacetonitrile (6) in the presence of NaNH2 in benzene gave a chiral cyclopropane derivative that was isolated as lactone 4 with 96% ee in 67% yield, after alkaline hydrolysis of the cyano group. The nucleophilic addition reaction of Grignard reagents to aldehyde 10, which was readily prepared from 4, proceeded highly selectively from the si-face to afford addition products 11 in high yields. Although hydride reduction of the corresponding ketone 15b, prepared from 11b, with L-Selectride also proceeded highly diastereo selectively, the facial selectivity was reversed to give the re-face addition product 11b. On the other hand, reduction of 15 with DIBAL-H afforded the si-face addition product 12 in high yields. These results suggested that these nucleophilic addition reactions proceeded via either the bisected s-trans or s-cis conformation of the cyclopropylcarbonyl derivatives. From 11 and 12, the target conformationally resticted analogs, 2 and 3, were synthesized, respectively. Starting from (S)-epichlorohydrin [(S)-5], their corresponding enantiomers, ent-a and ent-3, were also synthesized. The structures of the conformationally restricted analogs detected by the X-ray crystallographic analysis suggested that their conformations can be restricted as we hypothesized. Thus, a new method for restricting the conformation of cyclopropane derivatives has been developed.

  DOI：

  10.1021/jo9518056

文献信息

• Synthesis of (+)- and (−)-milnaciprans and their conformationally restricted analogs
  作者：Satoshi Shuto、Shizuka Ono、Yukako Hase、Noriko Kamiyama、Akira Matsuda

  DOI：10.1016/0040-4039(95)02221-x

  日期：1996.1

  converted to (+)-milnacipran [(+)-1], by which the absolute stereochemistry of (+)-1 was confirmed. (1S,2R)-1-Phenyl-2-[(S)-1-aminoethyl]-cyclopropane-N,N-diethylcarboxamindes (2), a conformationally restricted analog of 1, was also synthesized in high enantiomeric purity from 4. Starting from (S)-epichlorohydrin [(S)-5], their corresponding enantiomers, namely (−)-milnacipran [(−)-1] and ent-2, were

  （R）-表氯醇[（R）-5 ]与苯乙腈（6）在NaNH 2的存在下在苯中的反应生成环丙烷衍生物，其被分离为内酯4 [（1 S，2 R）-2-氧-在氰基进行碱性水解后，96％ee的1-苯基-3-氧杂双环[3,1,0]己烷]的收率为67％。化合物4容易地转化为（+）-米那普仑[（+）- 1 ]，由此证实了（+）- 1的绝对立体化学。（1 S，2 R）-1-苯基-2-[（（S）-1-氨乙基]-环丙烷-N，N-diethylcarboxamindes（2），构象受限的1的类似物，还从4合成高对映体纯度。从（S）-表氯醇[（S）-5 ]开始，还合成了它们相应的对映异构体，即（-）-米那普仑[（-）- 1 ]和ent-2 。
• Conformational Restriction by Repulsion between Adjacent Substituents on a Cyclopropane Ring:  Design and Enantioselective Synthesis of 1-Phenyl-2-(1-aminoalkyl)-<i>N,N</i>-diethylcyclopropanecarboxamides as Potent NMDA Receptor Antagonists
  作者：Satoshi Shuto、Shizuka Ono、Yukako Hase、Noriko Kamiyama、Hironao Takada、Kanako Yamasihita、Akira Matsuda

  DOI：10.1021/jo9518056

  日期：1996.1.1

  Adjacent substituents on a cyclopropane ring mutually exert steric repulsion quite significantly, because they are fixed in eclipsed conformation to each other. Based on this structural feature of the cyclopropane ring, conformationally restricted analogs of milnacipran (1), namely 1-phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides (2, 3, ent-2, and ent-3) were designed as potent NMDA receptor antagonists and were synthesized highly enantioselectively. Reaction of (R)epichlorohydrin [(R)-5] and phenylacetonitrile (6) in the presence of NaNH2 in benzene gave a chiral cyclopropane derivative that was isolated as lactone 4 with 96% ee in 67% yield, after alkaline hydrolysis of the cyano group. The nucleophilic addition reaction of Grignard reagents to aldehyde 10, which was readily prepared from 4, proceeded highly selectively from the si-face to afford addition products 11 in high yields. Although hydride reduction of the corresponding ketone 15b, prepared from 11b, with L-Selectride also proceeded highly diastereo selectively, the facial selectivity was reversed to give the re-face addition product 11b. On the other hand, reduction of 15 with DIBAL-H afforded the si-face addition product 12 in high yields. These results suggested that these nucleophilic addition reactions proceeded via either the bisected s-trans or s-cis conformation of the cyclopropylcarbonyl derivatives. From 11 and 12, the target conformationally resticted analogs, 2 and 3, were synthesized, respectively. Starting from (S)-epichlorohydrin [(S)-5], their corresponding enantiomers, ent-a and ent-3, were also synthesized. The structures of the conformationally restricted analogs detected by the X-ray crystallographic analysis suggested that their conformations can be restricted as we hypothesized. Thus, a new method for restricting the conformation of cyclopropane derivatives has been developed.