(S)-3-(4-chlorophenyl)-4-nitrobutanoic acid | 750649-51-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (S)-3-(4-chlorophenyl)-4-nitrobutanoic acid
• 英文别名: (3S)-3-(4-chlorophenyl)-4-nitrobutanoic acid
• CAS: 750649-51-5
• 化学式: C₁₀H₁₀ClNO₄
• 分子量: 243.647
• InChiKey: KYJIWWFRFAYPGO-MRVPVSSYSA-N

物化性质

• 熔点：
  78-79 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  417.9±40.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(4-chlorophenyl)-4-nitrobutanoic acid 在 镍 氢气 、 盐酸 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、506.62 kPa 条件下， 反应 24.0h， 以91%的产率得到S(-)-巴氯芬盐酸盐
  参考文献：
  名称：

  Synthesis of both enantiomers of baclofen using (R)- and (S)-N-phenylpantolactam as chiral auxiliaries

  摘要：

  Esterification of racemic 4-nitro-3-(4-chlorophenyl)butanoic acid with (R)- or (S)-N-phenylpantolactam as the chiral auxiliary allowed us to obtain the (3R,3'R)- or (3S,3'S)-nitro esters with > 98:2 dr after column chromatography. Hydrolysis of the resulting diastereopure nitro esters gave the corresponding enantiopure nitro acids, which were readily converted in high yields into either (R)- or (S)-baclofen hydrochloride. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.05.021
• 作为产物：
  描述：

  对氯肉桂酸 在 盐酸 、 4-二甲氨基吡啶 、 lithium hydroxide 、 氯化亚砜 、 苄基三乙基氯化铵 、 potassium carbonate 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 25.0h， 生成 (S)-3-(4-chlorophenyl)-4-nitrobutanoic acid
  参考文献：
  名称：

  Synthesis of both enantiomers of baclofen using (R)- and (S)-N-phenylpantolactam as chiral auxiliaries

  摘要：

  Esterification of racemic 4-nitro-3-(4-chlorophenyl)butanoic acid with (R)- or (S)-N-phenylpantolactam as the chiral auxiliary allowed us to obtain the (3R,3'R)- or (3S,3'S)-nitro esters with > 98:2 dr after column chromatography. Hydrolysis of the resulting diastereopure nitro esters gave the corresponding enantiopure nitro acids, which were readily converted in high yields into either (R)- or (S)-baclofen hydrochloride. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.05.021

文献信息

• A short and convenient chemoenzymatic synthesis of both enantiomers of 3-phenylGABA and 3-(4-chlorophenyl)GABA (Baclofen)
  作者：Fulvia Felluga、Valentina Gombac、Giuliana Pitacco、Ennio Valentin

  DOI：10.1016/j.tetasy.2005.02.019

  日期：2005.4

  Both enantiomers of the pharmacologically active GABA analogues 4-amino-3-phenyl and 4-amino-3-(4-chlorophenyl)butyric acid (Baclofen) with high enantiomeric excesses were synthesized by a chemoenzymatic method involving α-chymotrypsin mediated kinetic resolutions of the corresponding 3-phenyl- and 3-(4-chlorophenyl)-4-nitrobutyric acid methyl ester precursors.

  具有高对映体过量的药理活性GABA类似物4-氨基-3-苯基和4-氨基-3-（4-氯苯基）丁酸（Baclofen）的两种对映体均通过化学酶法合成，涉及α-胰凝乳蛋白酶介导的动力学拆分。相应的3-苯基-和3-（4-氯苯基）-4-硝基丁酸甲酯前体。
• Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen, Phenibut, and Fluorophenibut
  作者：Sándor B. Ötvös、Patricia Llanes、Miquel A. Pericàs、C. Oliver Kappe

  DOI：10.1021/acs.orglett.0c03100

  日期：2020.10.16

  The two-step flow asymmetric synthesis of chiral γ-nitrobutyric acids as key intermediates of the GABA analogues baclofen, phenibut, and fluorophenibut is reported on a multigram scale. The telescoped process comprises an enantioselective Michael-type addition facilitated by a polystyrene-supported heterogeneous organocatalyst under neat conditions followed by in situ-generated performic acid-mediated

  作为 GABA 类似物巴氯芬、苯布丁和氟苯丁酸关键中间体的手性 γ-硝基丁酸的两步流不对称合成已在多克规模上得到报道。该叠套工艺包括在纯条件下由聚苯乙烯负载的非均相有机催化剂促进的对映选择性迈克尔型加成，然后原位产生过甲酸介导的醛氧化。与以前的批量方法相比，在生产率和可持续性方面取得了重大进步，可以轻松获取有价值的光学活性物质。
• Highly Enantioselective Organocatalytic Conjugate Addition of Nitromethane to α,β-Unsaturated Aldehydes: Three-Step Synthesis of Optically Active Baclofen
  作者：Liansuo Zu、Hexin Xie、Hao Li、Jian Wang、Wei Wang

  DOI：10.1002/adsc.200700353

  日期：2007.12.10

  An efficient, organocatalytic, highly enantioselective, conjugate addition reaction of nitromethane with α,β-unsaturated aldehydes has been developed. The process serves as the key step for a practical 3-step synthesis of chiral baclofen, an antispastic drug.

  已经开发了硝基甲烷与α，β-不饱和醛的有效的，有机催化的，高度对映选择性的共轭加成反应。该方法是手性巴氯芬（一种抗痉挛性药物）的实际3步合成的关键步骤。
• One-Pot Synthesis of (<i>S</i>)-Baclofen via Aldol Condensation of Acetaldehyde with Diphenylprolinol Silyl Ether Mediated Asymmetric Michael Reaction as a Key Step
  作者：Yujiro Hayashi、Daisuke Sakamoto、Daichi Okamura

  DOI：10.1021/acs.orglett.5b02839

  日期：2016.1.4

  An efficient asymmetric total synthesis of (S)-baclofen was accomplished via a one-pot operation from commercially available materials using sequential reactions, such as aldol condensation of acetaldehyde, diphenylprolinol silyl ether mediated asymmetric Michael reaction of nitromethane, Kraus–Pinnick oxidation, and Raney Ni reduction. Highly enantioenriched baclofen was obtained in one pot with a

  （S）-baclofen的有效不对称全合成反应是通过一锅操作使用顺序反应从市售材料完成的，该反应依次为乙醛的醛醇缩合，二苯基脯氨醇甲硅烷基醚介导的硝基甲烷不对称迈克尔反应，Kraus-Pinnick氧化和阮内妮还原。在一个锅中以4个反应的高收率获得了高度对映体富集的巴氯芬。
• Diphenylprolinol Silyl Ether as Catalyst of an Asymmetric, Catalytic, and Direct Michael Reaction of Nitroalkanes with α,β-Unsaturated Aldehydes
  作者：Hiroaki Gotoh、Hayato Ishikawa、Yujiro Hayashi

  DOI：10.1021/ol702545z

  日期：2007.12.1

  A catalytic enantioselective direct conjugate addition of nitroalkanes to alpha,beta-unsaturated aldehydes using diphenylprolinol silyl ether as an organocatalyst has been developed. Using this methodology as a key step, short syntheses of therapeutically useful compounds have also been accomplished.

  已经开发了使用二苯基脯氨醇甲硅烷基醚作为有机催化剂将硝基烷烃催化对映选择性直接共轭加成到α，β-不饱和醛上的方法。使用该方法作为关键步骤，也已经完成了对治疗有用化合物的短合成。