t-4-bromo-3-hydroxy-r-1-cyclohexanecarboxylic acid | 138008-17-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: t-4-bromo-3-hydroxy-r-1-cyclohexanecarboxylic acid
• 英文别名: (+/-)-4t-bromo-3c-hydroxy-cyclohexane-r-carboxylic acid；(+/-)-4t-Brom-3c-hydroxy-cyclohexan-r-carbonsaeure；(1R,3R,4R)-4-bromo-3-hydroxycyclohexane-1-carboxylic acid
• CAS: 138008-17-0
• 化学式: C₇H₁₁BrO₃
• 分子量: 223.067
• InChiKey: LUJDSUZGQFVQRA-HSUXUTPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  t-4-bromo-3-hydroxy-r-1-cyclohexanecarboxylic acid 在 sodium hydroxide 作用下， 以 异丙醇 为溶剂， 反应 96.0h， 生成 (1S,3R,4R)-4-hydroxy-3-methoxycyclohexane-1-carboxylic acid
  参考文献：
  名称：

  Regiochemical control of the ring-opening of 1,2-epoxides by means of chelating processes. 2. Synthesis and reactions of the cis- and trans-oxides of 4-[(benzyloxy)methyl]cyclohexene, 3-cyclohexenemethanol, and methyl 3-cyclohexenecarboxylate

  摘要：

  The synthesis of the diastereoisomeric epoxides cis-1b-d and trans-2b-d and the products of their ring-opening by various nucleophiles are described. The results of the ring-openings of the trans-epoxides 2b-d can be rationalized by combining stereoelectronic and conformational arguments. However, the regioselectivity of the ring-openings of the cis-epoxides 1b-d can, in principle, be influenced by the chelation of a metal ion by the oxygen atom of the epoxy group and that of the substituent on the 4-position. The results of the reactions of the cis-epoxides 1b-d indicate that, to some degree, chelation is indeed a factor. How important a factor it is is dependent both on the reaction conditions and on the concentration and nature of the metal ion. In the ring-openings of the cis-epoxides 1b and 1d, chelation seems to be a larger factor than it is in the ring-openings of cis-epoxide 1c. However, in no case is chelation as large a factor as it was in the ring-openings of the cis-epoxide 1a, which was studied earlier. On the other hand, the autocatalyzed methanolysis, under neutral conditions, of epoxy acid 1e, followed by CH2N2 methylation of the crude product, afforded a mixture of the two regioisomeric hydroxy ethers in which the C-2-type compound predominates. This result suggests that intramolecular hydrogen bonding may determine the reactive conformation of 1e.

  DOI：

  10.1021/jo00031a018
• 作为产物：
  描述：

  (1RS,4RS,5RS)-4-bromo-6-oxabicyclo<3.2.1>octan-7-one 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以14.4 g的产率得到t-4-bromo-3-hydroxy-r-1-cyclohexanecarboxylic acid
  参考文献：
  名称：

  Regiochemical control of the ring-opening of 1,2-epoxides by means of chelating processes. 2. Synthesis and reactions of the cis- and trans-oxides of 4-[(benzyloxy)methyl]cyclohexene, 3-cyclohexenemethanol, and methyl 3-cyclohexenecarboxylate

  摘要：

  The synthesis of the diastereoisomeric epoxides cis-1b-d and trans-2b-d and the products of their ring-opening by various nucleophiles are described. The results of the ring-openings of the trans-epoxides 2b-d can be rationalized by combining stereoelectronic and conformational arguments. However, the regioselectivity of the ring-openings of the cis-epoxides 1b-d can, in principle, be influenced by the chelation of a metal ion by the oxygen atom of the epoxy group and that of the substituent on the 4-position. The results of the reactions of the cis-epoxides 1b-d indicate that, to some degree, chelation is indeed a factor. How important a factor it is is dependent both on the reaction conditions and on the concentration and nature of the metal ion. In the ring-openings of the cis-epoxides 1b and 1d, chelation seems to be a larger factor than it is in the ring-openings of cis-epoxide 1c. However, in no case is chelation as large a factor as it was in the ring-openings of the cis-epoxide 1a, which was studied earlier. On the other hand, the autocatalyzed methanolysis, under neutral conditions, of epoxy acid 1e, followed by CH2N2 methylation of the crude product, afforded a mixture of the two regioisomeric hydroxy ethers in which the C-2-type compound predominates. This result suggests that intramolecular hydrogen bonding may determine the reactive conformation of 1e.

  DOI：

  10.1021/jo00031a018

文献信息

• Development of an Efficient Manufacturing Process for a Key Intermediate in the Synthesis of Edoxaban
  作者：Makoto Michida、Hideaki Ishikawa、Takeshi Kaneda、Shinya Tatekabe、Yoshitaka Nakamura

  DOI：10.1021/acs.oprd.8b00413

  日期：2019.4.19

  We report the development of a novel synthetic method to access a key intermediate in the synthesis of edoxaban. The main features of the new synthetic method are an improvement in the approach for the synthesis of a key chiral bromolactone, application of an interesting cyclization reaction utilizing neighboring group participation to construct a differentially protected 1,2-cis-diamine, and implementation

  我们报告了一种新型合成方法的开发，该方法可用于合成edoxaban的关键中间体。新的合成方法的主要特征是对关键手性溴内酯的合成方法进行了改进，利用邻近基团的参与进行有趣的环化反应以构建差异保护的1,2-顺式-二胺以及应用了塞子技术-流反应器技术可使不稳定的中间体反应成几百公斤规模。通过实施这些更改，可明显提高制备依多沙班的总产量，并导致更高效，更环保的生产过程。
• Lefamulin的中间体化合物及其在Lefamulin制备中的应用
  申请人：郑州依米花手性药物研究有限公司

  公开号：CN111170893B

  公开（公告）日：2022-04-26

  本发明公开了一种Lefamulin的中间体化合物及其在Lefamulin制备中的应用，以期解决现有技术中Lefamulin制备成本高、收率低的技术问题。本发明提供一种中间体化合物及其制备方法，并将上述中间体化合物在制备Lefamulin或Lefamulin相关的医药中间体中的应用。本发明克服了现有技术的生产过程中碰到的手性氧化缺乏手性诱导，造成目标化合物转化率非常低、成本非常高、工业化生产困难的缺陷；工业化应用时能够有效降低生产成本，且可以有效控制三废的产生，具有显著的经济效益和社会效益。
• Grewe et al., Chemische Berichte, 1956, vol. 89, p. 1978,1986
  作者：Grewe et al.

  DOI：——

  日期：——