(S)-4-氯-3-羟基丁酸甲酯 | 86728-93-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 中文名称: (S)-4-氯-3-羟基丁酸甲酯
• 中文别名: 4-氯-3-羟基丁酸甲酯；(R/S)4-氯-3-羟基丁酸甲酯；(3S)-4-氯-3-羟基丁酸甲酯
• 英文名称: methyl (S)-4-chloro-3-hydroxybutanoate
• 英文别名: (S)-4-chloro-3-hydroxybutyric acid methyl ester；(S)-methyl 3-hydroxy-4-chloroacetoacetate；methyl (S)-(-)-4-chloro-3-hydroxybutyrate；methyl (S)-4-chloro-3-hydroxybutyrate；methyl 4-choro-(S)-3-hydroxybutanoate；methyl S-4-chloro-3-hydroxybutyrate；(S)-methyl-4-chloro-3-hydroxybutyrate；methyl (3S)-4-chloro-3-hydroxybutanoate
• CAS: 86728-93-0
• 化学式: C₅H₉ClO₃
• 分子量: 152.578
• InChiKey: WMRINGSAVOPXTE-BYPYZUCNSA-N

物化性质

• 沸点：
  248.6±20.0 °C(Predicted)
• 密度：
  1.232±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (S)-Methyl-4-chloro-3-hydroxybutyrate
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: (S)-Methyl-4-chloro-3-hydroxybutyrate
CAS number: 86728-93-0

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C5H9ClO3
Molecular weight: 152.6

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, hydrogen chloride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (S)-4-氯-3-羟基丁酸甲酯 在 sodium tetrahydroborate 、 盐酸 、 水 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 13.0h， 以98%的产率得到(S)-4-氯-1,3-丁二醇
  参考文献：
  名称：

  WO2008/93955

  摘要：

  公开号：
• 作为产物：
  描述：

  4-氯乙酰乙酸甲酯 在 [RuCl2(benzene)]2 、 氢气 作用下， 以 甲醇 为溶剂， 52.0 ℃ 、5.0 MPa 条件下， 反应 24.0h， 以92%的产率得到
  参考文献：
  名称：

  内置具有手性BINAP配体的共轭微孔聚合物，可作为不对称氢化的有效催化剂†

  摘要：

  合成了一系列具有可调BET表面积的基于手性（R）-BINAP配体（BINAP-CMPs）的手性共轭微孔聚合物（CMP）。这些固体催化剂在与钌物种配位后，对于β-酮酯的不对称氢化显示出高活性和对映选择性。而且，CMP可以实现空间隔离。通过防止二聚体和三聚体的形成，BINAP-CMP对于Ir催化的奎奴定不对称氢化显示出比BINAP高得多的活性。

  DOI：

  10.1039/c5cy00038f

文献信息

• Biocatalytic Cascade for the Synthesis of Enantiopure β-Azidoalcohols and β-Hydroxynitriles
  作者：Joerg H. Schrittwieser、Iván Lavandera、Birgit Seisser、Barbara Mautner、Wolfgang Kroutil

  DOI：10.1002/ejoc.200900091

  日期：2009.5

  one-pot reaction sequence starting from prochiral α-chloroketones leading to enantiopure β-azidoalcohols and β-hydroxynitriles is described. Asymmetric bioreduction of α-chloroketones by hydrogen transfer catalysed by an alcohol dehydrogenase (ADH) established the stereogenic centre in the first step to furnish enantiopure chlorohydrin intermediates. Subsequent biocatalysed ring closure to the epoxide

  描述了从前手性 α-氯酮开始导致对映纯 β-叠氮醇和 β-羟基腈的三步、两酶、一锅反应序列。通过由醇脱氢酶 (ADH) 催化的氢转移对 α-氯酮进行不对称生物还原，在第一步中建立了立体中心，以提供对映纯的氯醇中间体。随后通过非选择性卤代醇脱卤酶 (Hhe) 催化环氧化物的生物催化闭环和用叠氮化物 N3- 或氰化物 CN- 的亲核开环进行完全保留构型，得到对映体纯的 β-叠氮醇和 β-羟基腈，分别。合成了各种光学纯 β-叠氮醇和 β-羟基腈的两种对映异构体。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
• Efficient asymmetric synthesis of chiral alcohols using high 2-propanol tolerance alcohol dehydrogenase <i>Sm</i>ADH2 <i>via</i> an environmentally friendly TBCR system
  作者：Zeyu Yang、Hengwei Fu、Wenjie Ye、Youyu Xie、Qinghai Liu、Hualei Wang、Dongzhi Wei

  DOI：10.1039/c9cy01794a

  日期：——

  Alcohol dehydrogenases (ADHs) together with the economical substrate-coupled cofactor regeneration system play a pivotal role in the asymmetric synthesis of chiral alcohols; however, severe challenges concerning the poor tolerance of enzymes to 2-propanol and the adverse effects of the by-product, acetone, limit its applications, causing this strategy to lapse. Herein, a novel ADH gene smadh2 was identified

  醇脱氢酶（ADHs）与经济的底物偶联辅因子再生系统一起在手性醇的不对称合成中起着关键作用。然而，有关酶对2-丙醇的耐受性差以及副产物丙酮的不利影响的严峻挑战限制了其应用，从而导致了该策略的失效。本文中，通过传统的基因组挖掘技术从嗜麦芽单胞菌中鉴定出一种新的ADH基因smadh 2 。将该基因克隆到大肠杆菌细胞中，然后表达以产生Sm ADH2。mADH2具有较宽的底物谱，即使在10.5 M（80％，v / v）浓度下也表现出出色的耐受性和对2-丙醇的卓越活性。此外，成功设计了新型恒温鼓泡塔反应器（TBCR）系统，以减轻气流对副产物丙酮的抑制作用，并连续补充2-丙醇。为了绿色合成，可以同时回收有机废物。在可持续系统中，在不增加外部辅酶的情况下，以高底物负载（> 150 g L -1）合成结构多样的手性醇。其中，约780 g L -1（6 M）乙酰乙酸乙酯在2.5 h内具有99.9％ee和7488
• Shifting the equilibrium of a biocatalytic cascade synthesis to enantiopure epoxides using anion exchangers
  作者：Joerg H. Schrittwieser、Iván Lavandera、Birgit Seisser、Barbara Mautner、Jeffrey H. Lutje Spelberg、Wolfgang Kroutil

  DOI：10.1016/j.tetasy.2009.02.035

  日期：2009.3

  successfully employed to shift the equilibrium of a one-pot, two-step, two-enzyme cascade reaction affording enantiopure epoxides starting from prochiral α-chloroketones. The α-chloroketones were asymmetrically reduced employing an alcohol dehydrogenase and then transformed further to the corresponding epoxides employing halohydrin dehalogenases. Each epoxide enantiomer could be obtained with up to 93% conversion

  负载氢氧化物的阴离子交换剂已成功用于改变一锅，两步，两酶级联反应的平衡，从而提供从前手性α-氯酮开始的对映体纯环氧化合物。用醇脱氢酶不对称还原α-氯酮，然后用卤代醇脱卤酶将其进一步转化为相应的环氧化物。可以以对映体纯的形式（＞ 99％ee）以高达93％的转化率获得每种环氧对映体。与以前的研究相反，由于α-氯酮还原过程中有利于卤代醇的形成，因此可以减少氢化物供体（2-丙醇）的量。
• Efficient Asymmetric Synthesis of Ethyl (<i>S</i>)-4-Chloro-3-hydroxybutyrate Using Alcohol Dehydrogenase <i>Sm</i>ADH31 with High Tolerance of Substrate and Product in a Monophasic Aqueous System
  作者：Zeyu Yang、Wenjie Ye、Youyu Xie、Qinghai Liu、Rong Chen、Hualei Wang、Dongzhi Wei

  DOI：10.1021/acs.oprd.0c00088

  日期：2020.6.19

  Bioreductions catalyzed by alcohol dehydrogenases (ADHs) play an important role in the synthesis of chiral alcohols. However, the synthesis of ethyl (S)-4-chloro-3-hydroxybutyrate [(S)-CHBE], an important drug intermediate, has significant challenges concerning high substrate or product inhibition toward ADHs, which complicates its production. Herein, we evaluated a novel ADH, SmADH31, obtained from

  醇脱氢酶（ADHs）催化的生物还原在手性醇的合成中起重要作用。然而，重要的药物中间体（（S）-4-氯-3-羟基丁酸乙酯（[ S）-CHBE]）的合成对于高底物或产物对ADH的抑制作用具有重大挑战，这使其生产变得复杂。本文中，我们评估了一种新的ADH，即Sm ADH31，它从嗜麦芽单胞菌的嗜麦芽孢杆菌基因组中获得，其可以耐受极高浓度（6 M）的底物和产物。的共表达的Sm ADH31和葡萄糖脱氢酶从枯草芽孢杆菌在大肠杆菌意味着高达660克L-在单相水性体系中，–1（4.0 M）4-氯乙酰乙酸乙酯已完全转化为（S）-CHBE，其ee值> 99.9％，时空产率高（2664 g L –1 d –1）。分子动力学模拟揭示了Sm ADH31的高活性和立体选择性。此外，由于Sm ADH31具有较宽的底物谱，因此还以高浓度（100–462 g L –1）合成了其他五种光学纯手性醇。所有这些化合物均充当重要的药物中间体，证明了Sm
• Mesoporous cross-linked polymer copolymerized with chiral BINAP ligand coordinated to a ruthenium species as an efficient heterogeneous catalyst for asymmetric hydrogenation
  作者：Qi Sun、Xiangju Meng、Xiao Liu、Xiaoming Zhang、Yan Yang、Qihua Yang、Feng-Shou Xiao

  DOI：10.1039/c2cc35192g

  日期：——

  We report here a successful preparation of a heterogeneous chiral catalyst from copolymerization of mesoporous cross-linked polymer with chiral BINAP ligands, followed by coordination of the BINAP with a ruthenium species, which exhibits high activity, excellent enantioselectivity, and extraordinary recyclability in asymmetric hydrogenation.

  我们在这里报告了一种成功的非均相手性催化剂的制备方法，该方法是由中孔交联聚合物与手性BINAP配体共聚，然后将BINAP与钌物种配位，该化合物在不对称氢化中表现出高活性，优异的对映选择性和出色的可回收性。