R(-)-4-氰基-3-羟基丁酸乙酯 | 141942-85-0

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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: R(-)-4-氰基-3-羟基丁酸乙酯
• 中文别名: 4-氰基-3-羟基-丁酸乙酯；侧链ATS-5；阿托伐他汀钙A5；(R)-(-)-4-氰基-3-羟基丁酸乙酯；阿托伐他汀钙中间体A5；阿托伐他汀钙中间体ATS-5；(R)-(-)-3-羟基-4-氰基丁酸乙酯；阿托伐他汀中间体；(R)-(-)-4-氰-3-羟基丁酸乙酯；阿伐他汀钙ATS-5；4-氰基-3-羟基丁酸乙酯；(R)-4-氰基-3-羟基丁酸乙酯；ATS-5；阿托伐他汀钙中间体 ATS-5；(R)-4-氰基-3-羟基-丁酸乙酯；阿托伐他汀钙 A5
• 英文名称: (R)-ethyl 4-cyano-3-hydroxybutyrate
• 英文别名: ethyl (R)-4-cyano-3-hydroxybutanoate；ethyl (R)-4-cyano-3-hydroxybutyrate；(R)-4-cyano-3-hydroxybutyric acid ethyl ester；(R)-ethyl-(3-hydroxy-4-cyano)-butanoate；(R)-ethyl 4-cyano-3-hydroxybutanoate；ethyl (R)-3-hydroxy-4-cyano-butyrate；ethyl (3R)-4-cyano-3-hydroxybutanoate
• CAS: 141942-85-0
• 化学式: C₇H₁₁NO₃
• mdl: MFCD00270839
• 分子量: 157.169
• InChiKey: LOQFROBMBSKWQY-ZCFIWIBFSA-N

物化性质

• 比旋光度：
  -5 º (neat)
• 沸点：
  270 °C(lit.)
• 密度：
  1.114 g/mL at 25 °C(lit.)
• 闪点：
  >230 °F
• 溶解度：
  可溶于氯仿（少量）、DMSO（少量）、甲醇（少量）
• 稳定性/保质期：
  如果按照规格使用和储存，则不会分解，也未有已知危险反应。请避免与氧化物和酸接触。

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.714
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  1
• 海关编码：
  2926909090
• 安全说明：
  S26,S36
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  请将贮藏器密封保存在阴凉干燥处，并确保工作环境有良好的通风或排气设施。

SDS

Name:	Ethyl (R)-4-cyano-3-hydroxybutanoate 99% Material Safety Data Sheet
Synonym:
CAS:	141942-85-0

Section 1 - Chemical Product MSDS Name:Ethyl (R)-4-cyano-3-hydroxybutanoate 99% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
141942-85-0	Ethyl (R)-4-cyano-3-hydroxybutanoate	99%	unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled.
Chronic:
Not available.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Get medical aid. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.
Extinguishing Media:
Use water spray, dry chemical, or foam. Do NOT use carbon dioxide.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Absorb spill with inert material (e.g. vermiculite, sand or earth), then place in suitable container.

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Section 7 - HANDLING and STORAGE
Handling:
Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 141942-85-0: Personal Protective Equipment Eyes: Not available.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Clear liquid
Color: light yellow
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: > 270 deg C
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: > 190 deg C (> 374.00 deg F)
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: Soluble.
Specific Gravity/Density: 1.114
Molecular Formula: C7H11NO3
Molecular Weight: 157.17

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
High temperatures, incompatible materials, light, exposure to moist air or water.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 141942-85-0 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Ethyl (R)-4-cyano-3-hydroxybutanoate - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
No information available.
IMO
No information available.
RID/ADR
No information available.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 141942-85-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 141942-85-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 141942-85-0 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途：

• 医药中间体，是降血脂药物阿伐他汀钙的主要原料
• 用作药品阿伐他汀的中间体
• 阿伐他汀钙中间体

反应信息

• 作为反应物：
  描述：

  R(-)-4-氰基-3-羟基丁酸乙酯 在 咪唑 、 2,6-二甲基吡啶 、 甲醇 、 sodium chlorite 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 正丁基锂 、 sodium azide 、 sodium dihydrogenphosphate dihydrate 、 2,4,6-三氯苯甲酰氯 、 D(+)-10-樟脑磺酸 、 potassium tert-butylate 、 四丁基氟化铵 、 碘 、 氧气 、 二异丁基氢化铝 、 碳酸氢钠 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 二异丙胺 、 9-硼双环[3.3.1]壬烷 、 间氯过氧苯甲酸 、 三苯基膦 、 三氟乙酸 、 copper(l) chloride 、 palladium dichloride 、 三甲基膦 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， -78.0~75.0 ℃ 、150.0 kPa 条件下， 反应 107.58h， 生成 伊沙匹隆
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF (1S,3S,7S,10R,11S,12S,16R)-7,11-DIHYDROXY-8,8,10,12,16-PENTAMETHYL-3-[(1E)-1-METHYL-2-(2-METHYL-4-THIAZOLYL)ETHENYL]-17-OXA-4-AZABICYCLO[14.1.0]HEPTADECANE-5,9-DIONE AND INTERMEDIATES THEREOF
  [FR] PROCÉDÉ DE PRÉPARATION DE (1S,3S,7S,10R,11S,12S,16R)-7,11-DIHYDROXY-8,8,10,12,16-PENTAMÉTHYL-3-[(1E)-1-MÉTHYL-2-(2-MÉTHYL-4-THIAZOLYL)ÉTHÉNYL]-17-OXA-4-AZABICYCLO[14.1.0]HEPTADÉCANE-5,9-DIONE ET DE SES INTERMÉDIAIRES

  摘要：

  公开号：

  WO2015087351A3
• 作为产物：
  描述：

  S(-)-4-氯-3-羟基丁酸乙酯 在 sodium cyanide 、 halohydrin dehalogenase 作用下， 以 aq. phosphate buffer 为溶剂， 反应 4.0h， 生成 R(-)-4-氰基-3-羟基丁酸乙酯
  参考文献：
  名称：

  通过卤代醇脱卤酶和硝化酶的一锅双酶级联反应高效合成（R）-3-羟基戊二酸乙酯

  摘要：

  一个有效的单釜bienzymatic乙基的合成（- [R选自乙基（）-3-羟基戊二酸（EHG）小号）-4-氯-3-羟基丁酸酯（ECHB）通过使用重组实现大肠杆菌分别表达细胞或共表达突变的卤代醇脱卤酶基因从根癌农杆菌AD1和腈水解酶基因拟南芥（Arabidopsis thaliana）。高浓度的ECHB和NaCN抑制了腈水解酶的活性。因此，通过批量添加高浓度（最高至0.9 mol L -1）的ECHB和NaCN进行分批实施一锅法。在1.2 mol L -1下成功实现了ECHB到EHG的生物转化一锅两步法浓缩底物。因此，这种一锅双酶转化应可用于合成这些重要的光学纯β-羟基羧酸。

  DOI：

  10.1002/cctc.201500061

文献信息

• Biphasic Bioelectrocatalytic Synthesis of Chiral β-Hydroxy Nitriles
  作者：Fangyuan Dong、Hui Chen、Christian A. Malapit、Matthew B. Prater、Min Li、Mengwei Yuan、Koun Lim、Shelley D. Minteer

  DOI：10.1021/jacs.0c01890

  日期：2020.5.6

  NAD-dependent dehydrogenase, the diaphorase modified biocathode was used to regenerate NADH to support the conversion from ethyl 4-chloroacetoacetate (COBE) to ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE) catalyzed by AdhS. The addition of methyl tert-butyl ether (MTBE) as an organic phase not only increased the uploading of COBE, but also prevented the spontaneous hydrolysis of COBE, extended the lifetime

  两个障碍限制了基于氧化还原酶的不对称合成的应用。一种是消耗高化学计量的还原辅因子。另一个是有机底物、中间体和产物在水相中的低溶解度。为了解决基于氧化还原酶的不对称合成的两个障碍，构建并应用了双相生物电催化系统。在本研究中，研究了乙醇脱氢酶 (AdhS) 和卤代醇脱卤酶 (HHDH) 催化的手性 β-羟基腈的制备作为生物电合成模型，因为它们是他汀类药物合成中的高价值中间体。心肌黄酶 (DH) 被茂钴修饰的聚（烯丙胺）氧化还原聚合物固定在电极表面（DH/Cc-PAA 生物电极）上，以实现有效的生物电催化 NADH 再生。由于 AdhS 是 NAD 依赖性脱氢酶，因此使用心肌黄酶修饰的生物阴极再生 NADH，以支持从 4-氯乙酰乙酸乙酯 (COBE) 向 (S)-4-氯-3-羟基丁酸乙酯 ((S)-CHBE) 的转化由 AdhS 催化。添加甲基叔丁基醚 (MTBE) 作为有机相不仅增加了 COBE
• Experimental and Computation Studies on<i>Candida antarctica</i>Lipase B-Catalyzed Enantioselective Alcoholysis of 4-Bromomethyl-β-lactone Leading to Enantiopure 4-Bromo-3-hydroxybutanoate
  作者：Jung Yun Lim、Nan Young Jeon、A-Reum Park、Bora Min、Bum Tae Kim、Seongsoon Park、Hyuk Lee

  DOI：10.1002/adsc.201200901

  日期：2013.6.17

  including statins, were synthesized from rac‐4‐bromomethyl‐β‐lactone through kinetic resolution. Candida antarctica lipase B (CAL‐B) enantioselectively catalyzes the ring opening of the β‐lactone with ethanol to yield ethyl (R)‐4‐bromo‐3‐hydroxybutanoate with high enantioselectivity (E>200). The unreacted (S)‐4‐bromomethyl‐β‐lactone was converted to ethyl (S)‐4‐bromo‐3‐hydroxybutanoate (>99% ee), which can

  光学纯的4-溴-3-羟基丁酸酯的两个对映异构体，是他汀类各种生物活性化合物合成中的重要手性结构单元，是通过动力学拆分从rac -4-溴甲基-β-内酯合成的。南极假丝酵母脂肪酶B（CAL-B）用乙醇对映体催化β-内酯的开环，生成对映选择性高（E > 200）的（R）-4-溴3-3-羟基丁酸乙酯。未反应的（S）-4-溴甲基-β-内酯转化为（S）-4-溴-3-羟基丁酸乙酯（> 99％ee），可以进一步转化为乙基（R）-4-氰基-3-羟基丁酸酯，通过乙醇中酸催化的开环反应 分子建模表明，快速反应对映异构体（R）-溴甲基-β-内酯的立体中心距离正在反应的羰基碳约2Å。此外，反应缓慢的对映体（S）-4-溴甲基-β-内酯在溴取代基和Leu278残基的侧链之间遇到空间位阻，而反应快速的对映体没有任何空间冲突。
• NOVEL PROCESS FOR THE SYNTHESIS OF 5-(4-FLUOROPHENYL)-1-[2-((2R,4R)-4-HYDROXY-6-OXO-TETRAHYDRO-PYRAN-2-YL)-ETHYL]-2-ISOPROPYL-4-PHENYL-1H-PYRROLE-3-CARBOXYLIC ACID PHENYLAMIDE
  申请人：——

  公开号：US20020133026A1

  公开（公告）日：2002-09-19

  An improved process for the preparation of 5-(4-fluorophenyl)-1-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-2-isopropyl-4-phenyl-1H-pyrrole-3-carboxylic acid phenylamide by a novel synthesis is described where methyl cyanoacetate is converted in eight operations or fewer to the desired product, as well as other valuable intermediates used in the process.

  描述了一种通过新型合成制备5-(4-氟苯基)-1-[2-((2R,4R)-4-羟基-6-氧代-四氢吡喃-2-基)-乙基]-2-异丙基-4-苯基-1H-吡咯烷-3-羧酸苯酰胺的改进工艺，其中将甲基氰乙酸酯在八个或更少的步骤中转化为所需产品，以及在该过程中使用的其他有价值的中间体。
• Continuous flow chemistry: a discovery tool for new chemical reactivity patterns
  作者：Jan Hartwig、Jan B. Metternich、Nikzad Nikbin、Andreas Kirschning、Steven V. Ley

  DOI：10.1039/c4ob00662c

  日期：——

  Continuous flow chemistry as a process intensification tool is well known. However, its ability to enable chemists to perform reactions which are not possible in batch is less well studied or understood. Here we present an example, where a new reactivity pattern and extended reaction scope has been achieved by transferring a reaction from batch mode to flow. This new reactivity can be explained by

  作为过程增强工具的连续流化学是众所周知的。然而，其使化学家进行批量反应不可能的能力的研究或了解较少。在这里，我们提供一个示例，其中通过将反应从分批模式转移到流动模式，实现了新的反应模式和扩展的反应范围。这种新的反应性可以通过抑制回混和精确控制流动反应器装置中的温度来解释。
• [EN] IMPROVED SYNTHETON SYNTHESIS<br/>[FR] SYNTHESE DE SYNTHETON AMELIORE
  申请人：SK ENERGY AND CHEMICAL INC

  公开号：WO2004031131A1

  公开（公告）日：2004-04-15

  The present disclosure relates to an improved synthesis of the commercially important syntheton ECHB starting from the readily available 3-hydroxy-Ϝ-butyrolactone. The reaction employs a single pot procedure without isolation or purification of the intermediates. It has the advantage over procedures previously employed in the art of using reagents and conditions which minimize undesired side reactions and which can be readily employed at commercial scale. The product is produced in high yield and is readily purified to provide an excellent intermediate for further synthesis of commercially important products such as L-carnitine and the pharmaceutically important active substances used in HMG-coA reductase inhibitor products such as Lipitorè.

  本公开涉及一种改进的合成方法，用于从易获得的3-羟基-Ϝ-丁内酯出发合成商业重要的合成物ECHB。该反应采用一锅法进行，无需分离或纯化中间体。与先前在艺术中使用的程序相比，它具有优势，使用试剂和条件可以最大程度地减少不良副反应，并且可以轻松在商业规模上使用。产物产率高，并且可以轻松纯化，为进一步合成商业重要产品（如左旋肉碱和用于HMG-CoA还原酶抑制剂产品（如利普妥）中的药用重要活性物质）提供优质中间体。