1-苄基-4-哌啶甲醇 | 67686-01-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-苄基-4-哌啶甲醇
• 中文别名: (1-苯基-4-哌啶基)甲醇；N-苄基-4-哌啶甲醇；N-苄基哌啶-4-甲醇；1-苄基-4-羟甲基哌啶；1-苄基哌啶-4-甲醇；(1-苄基哌啶-2)-甲醇
• 英文名称: 1-benzyl-4-piperidinemethanol
• 英文别名: (1-benzylpiperidin-4-yl)methanol；N-benzyl-4-piperidinemethanol；1-benzyl-4-hydroxymethyl-piperidine；N-benzyl-4-hydroxymethylpiperidine；N-benzylpiperidine-4-methanol；(N-benzylpiperidin-4-yl)methanol；(1-benzyl-4-piperidyl)methanol
• CAS: 67686-01-5
• 化学式: C₁₃H₁₉NO
• mdl: MFCD00831014
• 分子量: 205.3
• InChiKey: FLQPYEOKVZYXRL-UHFFFAOYSA-N

物化性质

• 沸点：
  135-138°C (0.2 mmHg)
• 密度：
  1.056±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933399090
• 安全说明：
  S24/25
• WGK Germany：
  3
• 危险性防范说明：
  P280,P305+P351+P338,P310
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  室温

SDS

Name:	(1-Benzyl-4-piperidyl)methanol 97% Material Safety Data Sheet
Synonym:
CAS:	67686-01-5

Section 1 - Chemical Product MSDS Name:(1-Benzyl-4-piperidyl)methanol 97% Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
67686-01-5	(1-Benzyl-4-piperidyl)methanol	97	unlisted

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

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Not available.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. May be harmful if swallowed.
Inhalation:
May cause 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.
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, carbon dioxide, or chemical foam.

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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:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 67686-01-5: 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: Liquid
Color: colorless
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: Not available.
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C13H19NO
Molecular Weight: 205

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents, acids, reducing agents, acid chlorides.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 67686-01-5 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(1-Benzyl-4-piperidyl)methanol - 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: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 67686-01-5: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 67686-01-5 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 67686-01-5 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

简介

1-苄基-4-哌啶甲醇作为盐酸多奈哌齐的重要中间体，属于乙酰胆碱酯酶抑制剂，是一种长效治疗阿尔茨海默病（Alzheimer's disease, AD）的药物。该药由日本卫材株式会社研制开发，于1997年在美国首次上市，并已在世界70多个国家销售。

产品特点

1-苄基-4-哌啶甲醇的特点是剂量低、毒副作用小且耐受性好，在阿尔茨海默症治疗药物中占据重要地位。

合成方法

文献报道，以1-苄基-4-哌啶酮为原料，在氢化钠存在下与三甲基碘氧化锍（Me3S(O)I）进行Corey-Chaykovsky反应得到环氧化物，再经四氢铝锂开环得到目标产物。该合成路线的两步收率为42.3%。

反应信息

• 作为反应物：
  描述：

  1-苄基-4-哌啶甲醇 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以96%的产率得到1-苄基-4-哌啶甲醛
  参考文献：
  名称：

  Industrially Scalable Synthesis of Anti-alzheimer Drug Donepezil

  摘要：

  本文描述了一种简单、高效且具有工业可扩展性的多奈哌齐盐酸盐的全合成。文章还报告了合成多奈哌齐中间体2-(1-苄基哌啶-4-yl甲烯基)-5,6-二甲氧基茚-1-酮的X射线研究。2-(1-苄基哌啶-4-yl甲烯基)-5,6-二甲氧基茚-1-酮的晶体结构分析显示，其在空间组P121/c1中以单斜晶系结晶，晶胞参数为：a = 17.2992(7) Å，b = 10.1999(4) Å，c = 11.9539(5) Å，β = 103.450(2)°，体积V = 2051.42(15) ų，Z = 4。

  DOI：

  10.14233/ajchem.2017.20716
• 作为产物：
  描述：

  N-乙烯基咔唑 在 氢气 作用下， 70.0 ℃ 、370.01 kPa 条件下， 反应 3.0h， 以99.1%的产率得到1-苄基-4-哌啶甲醇
  参考文献：
  名称：

  一种N-乙基咔唑的合成方法

  摘要：

  一种N‑乙基咔唑的合成方法，涉及N‑乙基咔唑。在N‑甲基吡咯烷酮溶剂中，将咔唑与去质子剂进行成盐反应，生成咔唑盐，继续通入乙炔反应后，得到N‑乙烯基咔唑；在生成的N‑乙烯基咔唑有机溶剂中，再加入Pd催化剂，在助剂中进行氢化反应，得到N‑乙基咔唑。优选了一系列特殊的催化剂，通过催化加氢工艺可以有效实现N‑乙基咔唑的绿色合成，减少三废排放。加氢过程中，催化剂可重复使用，降低成本。加氢工艺制备得到的N‑乙基咔唑产品质量更高。不需要传统烷基化试剂(硫酸二乙酯、碳酸乙酯、卤乙烷等)及有毒有机溶剂参与，无废液排放问题，是一条真正符合绿色清洁的生产工艺。

  公开号：

  CN107488140B

文献信息

• [EN] PYRROLOPYRIMIDINES<br/>[FR] PYRROLOPYRIMIDINES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2009016132A1

  公开（公告）日：2009-02-05

  The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are polo-like kinase (PLKs) inhibitors useful for the treatment of disease states mediated by PLK, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumour growth, rheumatoid arthritis, restenosis and atherosclerosis.

  本发明涉及化合物或其药用盐，制备它们的方法，含有它们的药物组合物以及它们在治疗中的用途。该发明特别涉及一类极化样激酶（PLKs）抑制剂化合物，用于治疗由PLK介导的疾病状态，特别是PLK4，特别是在治疗涉及异常细胞增殖的病理过程中有用的化合物，如肿瘤生长、类风湿性关节炎、再狭窄和动脉粥样硬化。
• Structure−Activity Relationship Studies of Novel 4-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-1-(3-phenylpropyl)piperidine Analogs:  Synthesis and Biological Evaluation at the Dopamine and Serotonin Transporter Sites
  作者：Aloke K. Dutta、Cen Xu、Maarten E. A. Reith

  DOI：10.1021/jm9506581

  日期：1996.1.1

  Several analogs of the potent dopamine (DA) transporter ligand 4-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-1-(3-phenylpropyl)piperidine, 1b, were made and biologically evaluated for their binding at the DA and serotonin (5HT) transporters in rat striatal membranes. Different alkyl chain lengths and substitutions were introduced in these molecules to generate an optimum activity and selectivity for the

  制备了强效多巴胺（DA）转运蛋白配体4- [2- [双（4-氟苯基）-甲氧基]乙基] -1-（3-苯基丙基）哌啶的类似物1b，并对其在生物学上的结合进行了生物学评估。大鼠纹状体膜中的DA和血清素（5HT）转运蛋白。在这些分子中引入了不同的烷基链长度和取代基，以产生针对DA转运蛋白的最佳活性和选择性。通常，未取代的和氟取代的化合物对于DA转运蛋白是最活跃和最具选择性的。化合物4- [2-（二苯基甲氧基）乙基] -1-苄基哌啶9a显示出高效价，并且在该系列化合物中对DA转运蛋白的选择性最高（5HT / DA = 49）。发现其中一些新颖的类似物比原始GBR 12909分子在DA转运蛋白上的结合更具选择性，
• COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
  申请人：CHIESI FARMACEUTICI S.p.A.

  公开号：US20160235734A1

  公开（公告）日：2016-08-18

  Compounds of formula I, defined herein, act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for treating broncho-obstructive and inflammatory diseases.

  具有本公式I定义的化合物既作为毒蕈碱受体拮抗剂又作为β2肾上腺素能受体激动剂，并且用于治疗支气管阻塞和炎症性疾病。
• Compounds IV
  申请人：Higginbottom Michael

  公开号：US20090203695A1

  公开（公告）日：2009-08-13

  The present application relates to new compounds of formula (I), to pharmaceutical compositions comprising the compounds, to processes for their preparation, and to the use of the compounds as leptin receptor modulator mimetics in the preparation of medicaments against conditions associated with weight gain, type 2 diabetes and dyslipidemias.

  本申请涉及式(I)的新化合物，包含该化合物的药物组合物，它们的制备过程，以及将这些化合物用作瘦素受体调节剂拟态物，用于制备治疗与体重增加、2型糖尿病和高脂血症相关的药物。
• Nickel-Catalyzed Hydrogen-Borrowing Strategy for α-Alkylation of Ketones with Alcohols: A New Route to Branched <i>gem</i>-Bis(alkyl) Ketones
  作者：Jagadish Das、Khushboo Singh、Mari Vellakkaran、Debasis Banerjee

  DOI：10.1021/acs.orglett.8b02256

  日期：2018.9.21

  The α-alkylation of ketones using an earth-abundant and nonprecious NiBr2/L1 system is reported. This nickel-catalyzed reaction could be performed in gram scale and successfully applied in the synthesis of donepezil (Alzheimer’s drug) and functionalization of steroid hormones and fatty acid derivatives. Synthesis of N-heterocycles, methylation of ketones, and one-pot double alkylation to bis-hetero

  据报道，使用一种地球上丰富的非贵重的NiBr 2 / L1系统对酮进行α-烷基化。该镍催化的反应可以以克为单位进行，并成功地用于多奈哌齐的合成（阿尔茨海默氏病药物）以及类固醇激素和脂肪酸衍生物的功能化。N-杂环的合成，酮的甲基化以及使用两种不同的醇和单一催化剂将一锅双烷基化为双-杂芳基酮，拓宽了催化规程的范围。使用定义的Ni-H物种和氘标记实验的初步机理研究确定了借用氢策略的参与。