(S)-2-methyl-3-(2'-bromo-5'-methoxyphenyl)propionic acid | 203380-43-2

• 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)-2-methyl-3-(2'-bromo-5'-methoxyphenyl)propionic acid
• 英文别名: (2S)-3-(2-bromo-5-methoxyphenyl)-2-methylpropanoic acid
• CAS: 203380-43-2
• 化学式: C₁₁H₁₃BrO₃
• 分子量: 273.126
• InChiKey: OUMJKBFCSIGAMA-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-methyl-3-(2'-bromo-5'-methoxyphenyl)propionic acid 在 硼烷四氢呋喃络合物 作用下， 生成 (2S)-(2'-bromo-5'-methoxyphenyl)-2-methylpropan-1-ol
  参考文献：
  名称：

  一种新型的三氧化铬催化的伯醇氧化为羧酸

  摘要：

  报道了新颖的CrO 3催化的伯醇氧化为羧酸。在湿式MeCN中，仅用1-2 mol％的CrO 3和2.5当量的H 5 IO 6即可顺利进行氧化，从而以极佳的收率得到羧酸。对于具有相邻手性中心的醇，未观察到明显的外消旋作用。仲醇被干净地氧化成酮。

  DOI：

  10.1016/s0040-4039(98)00987-3
• 作为产物：
  描述：

  2-溴-5-甲氧基苯甲酸 在 盐酸 、 sodium tetrahydroborate 、 氯化亚砜 、 三氟化硼乙醚 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 (S)-2-methyl-3-(2'-bromo-5'-methoxyphenyl)propionic acid
  参考文献：
  名称：

  Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist

  摘要：

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.

  DOI：

  10.1021/jo991292t

文献信息

• Asymmetric conjugate addition reaction
  申请人：Merck & Co., Inc.

  公开号：US06353110B1

  公开（公告）日：2002-03-05

  This invention relates to a key intermediate in the synthesis of an endothelin antagonist the synthesis of this key intermediate via an asymmetric conjugate addition reaction.

  这项发明涉及一种内皮素拮抗剂合成中的关键中间体，通过不对称共轭加成反应合成这种关键中间体。
• A novel chromium trioxide catalyzed oxidation of primary alcohols to the carboxylic acids
  作者：Mangzhu Zhao、Jing Li、Zhiguo Song、Richard Desmond、David M. Tschaen、Edward J.J. Grabowski、Paul J. Reider

  DOI：10.1016/s0040-4039(98)00987-3

  日期：1998.7

  A novel CrO3 catalyzed oxidation of primary alcohols to the carboxylic acids is reported. The oxidation proceeds smoothly with only 1–2 mol % of CrO3 and 2.5 equivalents of H5IO6 in wet MeCN to give the carboxylic acids in excellent yield. No significant racemization is observed for alcohols with adjacent chiral centers. Secondary alcohols are cleanly oxidized to ketones.

  报道了新颖的CrO 3催化的伯醇氧化为羧酸。在湿式MeCN中，仅用1-2 mol％的CrO 3和2.5当量的H 5 IO 6即可顺利进行氧化，从而以极佳的收率得到羧酸。对于具有相邻手性中心的醇，未观察到明显的外消旋作用。仲醇被干净地氧化成酮。
• Oxidation of Primary Alcohols to Carboxylic Acids with Sodium Chlorite Catalyzed by TEMPO and Bleach
  作者：Mangzhu Zhao、Jing Li、Eiichi Mano、Zhiguo Song、David M. Tschaen、Edward J. J. Grabowski、Paul J. Reider

  DOI：10.1021/jo982143y

  日期：1999.4.1
• OXIDATION OF PRIMARY ALCOHOLS TO CARBOXYLIC ACIDS WITH SODIUM CHLORITE CATALYZED BY TEMPO AND BLEACH: 4-METHOXYPHENYLACETIC ACID
  作者：Zhao, Matthew M.、Li, Jing、Mano, Eiichi、Song, Zhiguo J.、Tschaen, David M.、Ghosh, Arun、Sieser, Jamie、Cai, Weiling、Kelly, Sarah E.

  DOI：10.15227/orgsyn.081.0195

  日期：——
• Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist
  作者：Zhiguo J. Song、Mangzhu Zhao、Richard Desmond、Paul Devine、David M. Tschaen、Richard Tillyer、Lisa Frey、Richard Heid、Feng Xu、Bruce Foster、Jing Li、Robert Reamer、Ralph Volante、Edward J. J.Grabowski,、Ulf H. Dolling、Paul J. Reider、Shigemitsu Okada、Yoshiaki Kato、Eiichi Mano

  DOI：10.1021/jo991292t

  日期：1999.12.1

  An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans-trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis-1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO2) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.