(S)-(-)-methyl 1,4-benzodioxan-2-carboxylate | 650597-66-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (S)-(-)-methyl 1,4-benzodioxan-2-carboxylate
• 英文别名: (S)-methyl 1,4-benzodioxane-2-carboxylate；methyl (3S)-2,3-dihydro-1,4-benzodioxine-3-carboxylate
• CAS: 650597-66-3
• 化学式: C₁₀H₁₀O₄
• mdl: MFCD00297092
• 分子量: 194.187
• InChiKey: SNLAAGHHNZECPE-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-(-)-methyl 1,4-benzodioxan-2-carboxylate 在 盐酸 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 24.0h， 生成 (2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(1H-imidazol-1-yl)methanone
  参考文献：
  名称：

  反应条件如何影响2-取代-1,4-苯并二恶烷衍生物的对映体纯合成？

  摘要：

  几种具有生物活性的化合物在结构上包括对映体2-取代-1,4-苯并二恶烷骨架。因此，影响涉及大多数常见化学反应物的反应的直接外消旋作用是至关重要的问题。因此，必须开发一种不影响对映体过量的完全立体控制的合成路线。建立可靠的手性HPLC方法，使其能够追踪反应并改善合成性能也很重要。在这里，我们报告了两种不同合成子的手性研究，我们专门评估了可以运行的合成途径以提供它们，从而避免了通常在碱性条件下可能发生的外消旋过程。此外，我们开发了独特的手性HPLC方法来拆分对映体，

  DOI：

  10.1002/chir.22968
• 作为产物：
  描述：

  1,4-苯并二烷-2-羧酸 在 sodium hydroxide 、 (+)-Dehydroabietylamine ethanoate 、 硫酸 、 原甲酸三甲酯 作用下， 以 甲醇 为溶剂， 反应 12.5h， 生成 (S)-(-)-methyl 1,4-benzodioxan-2-carboxylate
  参考文献：
  名称：

  A short entry to enantiopure 2-substituted 1,4-benzodioxanes by efficient resolution methods

  摘要：

  (R)-1,4-Benzodioxane-2-carboxilic acid (R)-1 was obtained by resolution of the racemic acid 1 with stoichiometric or nonstoichiometric (+)-dehydroabietylamine (+)-2 in high chemical yield and enantiomeric excess. (S)-1 was isolated from the mother liquors of the crystallisation of (R)-1-(+)-2 and its enantiomeric excess maximised by recrystallisation procedures involving a precipitation under kinetic control or, alternatively, by conversion into the methyl ester followed by a single crystallisation. The different mechanisms of the two S enrichments is well explained by the binary phase diagrams of the acid and of the ester, which show that the former is a racemic compound, whereas the latter a conglomerate. The DSC analyses were extended to 2-hydroxymethyl- and 2-mesyloxymethyl-1,4-benzodioxane, establishing that the alcohol forms a racemic compound, while its mesyl ester a conglomerate. On the basis of these results, different resolution strategies can be designed to obtain useful homochiral 2-substituted 1,4-benzodioxanes coupling the resolution of I via diastereomeric salt formation with the enantiomeric enrichments by recrystallisations, preferably of its conglomerate forming derivatives. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.09.012

文献信息

• Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation
  作者：Xuguang Yin、Yi Huang、Ziyi Chen、Yang Hu、Lin Tao、Qingyang Zhao、Xiu-Qin Dong、Xumu Zhang

  DOI：10.1021/acs.orglett.8b01469

  日期：2018.7.20

  Rh-catalyzed asymmetric hydrogenation of various benzo[b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation

  成功开发了Rh催化的各种苯并[ b ] [1,4]二恶英衍生物的不对称加氢反应，以使用ZhaoPhos和具有高取代度的ZhaoPhos配体的N-甲基化来制备手性2取代的2,3-二氢苯并[1,4]二恶烷衍生物。收率和出色的对映选择性（高达99％的收率，> 99％的对映体过量（ee），周转数（TON）= 24000）。此外，这种不对称氢化方法作为高达10000吨的关键步骤，已成功地用于开发高效的合成路线，以构建一些重要的生物活性分子，例如MKC-242，WB4101，BSF-190555和（R）-恶唑烷·HCl。
• Chemoenzymatic synthesis of piperoxan, prosympal, dibozane, and doxazosin
  作者：Abdul Rouf、Pankaj Gupta、Mushtaq A. Aga、Brijesh Kumar、Asha Chaubey、Rajinder Parshad、Subhash C. Taneja

  DOI：10.1016/j.tetasy.2012.10.018

  日期：2012.12

  The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (+/-)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee similar to 99%, E = 535) at 258 mmol (50 g/L) substrate concentration. (C) 2012 Elsevier Ltd. All rights reserved.
• From 2-Aminomethyl-1,4-benzodioxane Enantiomers to Unichiral 2-Cyano- and 2-Carbonyl-Substituted Benzodioxanes via Dichloroamine
  作者：Cristiano Bolchi、Ermanno Valoti、Valentina Straniero、Paola Ruggeri、Marco Pallavicini

  DOI：10.1021/jo500964y

  日期：2014.7.18

  2-Substituted 1,4-benzodioxanes, such as 2-cyano-, 2-methoxycarbonyl-, 2-aminocarbonyl-, and 2-formyl-1,4-benzodioxane, are key synthons that for the most part are never described as enantiomers or are inadequately characterized for enantiomeric purity. They were prepared by quantitative N,N-dichlorination of (R)- and (S)-2-aminomethyl-1,4-benzodioxane and successive functional group conversions in high yields without any racemization of the stereogenic benzodioxane C(2).