(R)-(-)-3-奎宁醇 | 25333-42-0

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 中文名称: (R)-(-)-3-奎宁醇
• 中文别名: 3-奎宁醇；(R)-奎宁环-3-醇；(R)-(-)-喹宁环-3-醇；R-3-奎宁环醇；(R)-(-)-氮杂双环[2,2,2]辛烷-3-醇；(R)-(-)-3-喹宁醇；(R)-(-)-1-氮杂双环[2.2.2]辛-3-醇；(R)-3-奎宁环醇
• 英文名称: (R)-quinuclidin-3-ol
• 英文别名: (R)-3-quinuclidinol；3-(R)-quinuclidinol；(R)-(-)-3-Quinuclidinol；(3R)-1-azabicyclo[2.2.2]octan-3-ol
• CAS: 25333-42-0
• 化学式: C₇H₁₃NO
• 分子量: 127.186
• InChiKey: IVLICPVPXWEGCA-ZETCQYMHSA-N

物化性质

• 熔点：
  217-224 °C
• 比旋光度：
  -44.5 º (c=3, 1N HCl)
• 沸点：
  120 °C (20.2527 mmHg)
• 密度：
  1.0083 (rough estimate)
• LogP：
  -2.8 at 20℃ and pH7
• 稳定性/保质期：

  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 安全说明：
  S16,S26,S36/37/39,S45
• 危险品运输编号：
  UN 3263
• 海关编码：
  2933990090
• 危险品标志：
  C
• 危险类别码：
  R34,R11

SDS

Name:	(R)-(-)-3-Quinuclidinol 99+% (GC) Material Safety Data Sheet
Synonym:	(R)-(-)-1-Azabicyclo[2.2.2]Octan-3-Ol; (R)-(-)-3-Hydroxyquinuclidine
CAS:	25333-42-0

Section 1 - Chemical Product MSDS Name:(R)-(-)-3-Quinuclidinol 99+% (GC) Material Safety Data Sheet
Synonym:(R)-(-)-1-Azabicyclo[2.2.2]Octan-3-Ol; (R)-(-)-3-Hydroxyquinuclidine

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
25333-42-0	(R)-(-)-3-Quinuclidinol	99+%	246-857-6

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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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. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or 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:

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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. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Runoff from fire control or dilution water may cause pollution.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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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# 25333-42-0: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
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: Powder
Color: white - beige
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: 120 deg C @ 27.00mb
Freezing/Melting Point: 217 - 220 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: 1
Decomposition Temperature:
Solubility in water: 100g/100ml water
Specific Gravity/Density:
Molecular Formula: C7H13NO
Molecular Weight: 127.19

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 25333-42-0 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(R)-(-)-3-Quinuclidinol - 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
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 25333-42-0: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 25333-42-0 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 25333-42-0 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：盐酸戊乙奎醚和索菲那新中间体

反应信息

• 作为反应物：
  描述：

  (R)-(-)-3-奎宁醇 在 palladium over charcoal 甲酸铵 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 Naronapride
  参考文献：
  名称：

  WO2007/149929

  摘要：

  公开号：
• 作为产物：
  描述：

  N-乙酸乙酯-4-哌啶甲酸乙酯 在 potassium tert-butylate 、 水 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 9.83h， 生成 (R)-(-)-3-奎宁醇
  参考文献：
  名称：

  一种光学活性3-奎宁醇的制备方法

  摘要：

  本发明涉及一种中间体的合成方法，属于有机合成领域。具体说是一种操作简便，成本低廉，适用于工业化生产的光学活性3‑奎宁醇的制备方法。以4‑哌啶甲酸为起始原料，通过酯化，亲核取代，Dieckmann缩合，脱羧，成盐，还原，乙酰化，化学拆分等得到中间体光学活性3‑奎宁醇。上述的反应式如下：

  公开号：

  CN107721999A
• 作为试剂：
  描述：

  2-phenyl-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid 在 叠氮磷酸二苯酯 、 三乙胺 、 (R)-(-)-3-奎宁醇 作用下， 以 甲苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.67h， 生成 2-phenyl-5,6-dihydro-4H-cyclopenta[b]thiophene-3-amine
  参考文献：
  名称：

  EP2119716

  摘要：

  公开号：

文献信息

• Engineering an Enantioselective Amine Oxidase for the Synthesis of Pharmaceutical Building Blocks and Alkaloid Natural Products
  作者：Diego Ghislieri、Anthony P. Green、Marta Pontini、Simon C. Willies、Ian Rowles、Annika Frank、Gideon Grogan、Nicholas J. Turner

  DOI：10.1021/ja4051235

  日期：2013.7.24

  catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development

  开发用于生产对映异构纯手性胺的经济高效且可持续的催化方法是制药和精细化工行业面临的关键挑战。据估计，40-45% 的候选药物含有手性胺，这突显了这一挑战，这推动了对以高产率和对映体过量提供目标结构的广泛适用的合成方法的需求。在此，我们描述了来自黑曲霉 (MAO-N) 的单胺氧化酶变体“工具箱”的开发和应用，该变体显示出显着的底物范围和对空间要求基序的耐受性，包括一个新变体，它对含有以下物质的底物表现出高活性和对映选择性氨基二苯甲烷（二苯甲基胺）模板。通过将合理的结构导向工程与高通量筛选相结合，可以扩大 MAO-N 的底物范围以适应含有大量芳基取代基的胺底物。这些工程化的 MAO-N 生物催化剂已应用于去消旋反应，用于高效不对称合成仿制药活性药物成分索利那新和左西替利嗪以及天然产物 (R)-coniine、(R)-eleagnine 和 (R)-leptaflorine . 我们还报告了一种新的
• [EN] A NOVEL 4-METHYLBENZENESULPHONATE SALT AND A PROCESS FOR PREPARING A PHARMACEUTICAL COMPOSITION COMPRISING THE SALT<br/>[FR] NOUVEAU SEL 4-MÉTHYLBENZÈNESULPHONATE ET PROCÉDÉ DE PRÉPARATION D'UNE COMPOSITION PHARMACEUTIQUE COMPRENANT LE SEL
  申请人：ASTRAZENECA AB

  公开号：WO2010144043A1

  公开（公告）日：2010-12-16

  The invention provides a 4-methylbenzenesulphonate salt of the muscarinic antagonist (R)- 1-(4-fluorophenethyl)-3-((S)-2-phenyl-2-(piperidin-1 -yl)propanoyloxy)-1- azoniabicyclo[2.2.2]octane and its use in therapy,as well as a process for preparing a pharmaceutical composition comprising the salt and its use in therapy.

  这项发明提供了马来酸甲基苯磺酸盐（R）-1-（4-氟苯乙基）-3-（（S）-2-苯基-2-（哌啶-1-基）丙酰氧基）-1-氮杂双环[2.2.2]辛烷的肌肉收缩素拮抗剂，以及用于治疗的方法，以及制备包含该盐的药物组合物的方法和用途。
• 一种阿地溴铵合成及纯化的新方法
  申请人：安徽赛诺制药有限公司

  公开号：CN108794464A

  公开（公告）日：2018-11-13

  本发明公开了一种阿地溴铵合成及纯化的新方法，该方法使用四氢呋喃，使用的卤代烷作为引发剂，采用酸化后溶剂萃取和重结晶获得成品，本发明公开的制备工艺反应条件温和，操作简便，收率高，成品纯度高，为国内该项工艺作出突破性进展。
• [EN] A PROCESS FOR PREPARING ACLIDINIUM BROMIDE AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE BROMURE D'ACLIDINIUM ET DE SES INTERMÉDIAIRES
  申请人：GBR LABORATORIES PVT LTD

  公开号：WO2018150437A1

  公开（公告）日：2018-08-23

  Provided herein is a process for synthesis of aclidinium bromide and intermediates thereof, wherein the process for the preparation of aclidinium bromide increases the % yield of aclidinium bromide by about 70% to 90%.

  本文提供了一种合成阿克利迪尼溴化物及其中间体的方法，其中用于制备阿克利迪尼溴化物的方法将阿克利迪尼溴化物的产率提高约70%至90%。
• Antimuscarinic bronchodilators
  申请人：Pfizer Inc.

  公开号：US05292749A1

  公开（公告）日：1994-03-08

  ##STR1## 3-Quinuclidinyl butanoate and propanoate antimuscarinic bronchodilators, particularly useful in the treatment of chronic obstructive airways disease and asthma, of formula (1), and their pharmaceutically acceptable salts, wherein X is either (a) a phenyl group optionally substituted by one or two substituents each independently selected from halo. CF.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy and hydroxy or (b) a thienyl group; and "Het" is either (a) a 5-membered nitrogen-containing heterocyclic group attached to the adjacent carbon atom either by a carbon or a ring nitrogen atom and which is selected from imidazolyl, pyrazolyl, triazolyl and tetrazolyl. (b) an oxadiazolyl or thiadiazolyl group attached to the adjacent carbon atom by a carbon atoms, or (c) a 6-membered nitrogen-containing heterocyclic group attached to the adjacent carbon atom by a carbon atom and selected from pyridinyl, pyrazinyl, pyrimidinyl and pyridazinyl, "Het" being optionally substituted by up to two substituents each independently selected from halo, CF.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, amino and azido; and m is 1 or 2.

  3-喹啉基丁酸丁酯和丙酸丙酯抗胆碱能支气管扩张剂，特别适用于慢性阻塞性气道疾病和哮喘的治疗，其化学式（1），及其药学上可接受的盐，其中X是（a）苯基，可选择一个或两个取代基，每个取代基独立选择自卤素、三氟甲基、C1-C4烷基、C1-C4烷氧基和羟基，或（b）噻吩基；“Het”是（a）5-成员含氮杂环基，通过相邻碳原子或环氮原子连接到相邻碳原子，可选择自咪唑基、吡唑基、三唑基和四唑基，或（b）通过碳原子连接到相邻碳原子的氧代二唑基或硫代二唑基，或（c）通过碳原子连接到相邻碳原子的6-成员含氮杂环基，可选择自吡啶基、吡嗪基、嘧啶基和吡啶嗪基，“Het”可选择一个或两个取代基，每个取代基独立选择自卤素、三氟甲基、C1-C4烷基、C1-C4烷氧基、羟基、氨基和叠氮基；m为1或2。