2-氯-1-(3,4-二氟苯基)乙酮 | 51336-95-9

• 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 - 有机氧化合物
• 中文名称: 2-氯-1-(3,4-二氟苯基)乙酮
• 中文别名: 3`,4`-二氟-2-氯苯乙酮；2-氯-3',4'-二氟苯乙酮
• 英文名称: 2-chloro-1-(3,4-difluorophenyl)ethan-1-one
• 英文别名: 2-chloro-1-(3,4-difluorophenyl)ethanone；2-chloro-1-(3,4-difuorophenyl)ethanone；2-chloro-3',4'-difluoroacetophenone；2-chloro-1-(3,4-difluorophenyl)-ethanone；2-chloro-1-(3,4-difluoro-phenyl)-ethanone；2-chloro-1-(3,4-difluoro-phenyl)ethanone
• CAS: 51336-95-9
• 化学式: C₈H₅ClF₂O
• mdl: MFCD03966888
• 分子量: 190.577
• InChiKey: VMEDAWUIKFAFJQ-UHFFFAOYSA-N

物化性质

• 熔点：
  31-32 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  256.3±25.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)
• 溶解度：
  溶于甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi,C
• 海关编码：
  2914700090
• 包装等级：
  II
• 危险类别：
  8
• 危险性防范说明：
  P234,P260,P264,P280,P301+P330+P331+P310,P303+P361+P353+P310+P363,P304+P340+P310,P305+P351+P338+P310,P390,P405,P406,P501
• 危险品运输编号：
  3261
• 危险性描述：
  H290,H314
• 储存条件：
  存储条件：2-8℃，干燥，避光

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 2-Chloro-1-(3,4-difluoro-phenyl)-ethanone
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: 2-Chloro-1-(3,4-difluoro-phenyl)-ethanone
CAS number: 51336-95-9

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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, refrigerated.
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: C8H5ClF2O
Molecular weight: 190.6

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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, hydrogen fluoride.

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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

制备方法与用途

2-氯-1-(3,4-二氟苯基)乙酮是一种重要的精细化工中间体，广泛用于有机合成及医药实验研究。

其制备步骤如下：

迅速称取10.2g无水三氯化铝（研细），加入干燥的四口烧瓶中。立即加入11.4mL邻二氟苯（已干燥），并安装电动搅拌器、温度计和恒压滴液漏斗（装有纯化的乙酸酐）。球形冷凝管上部接一装有无水氯化钙的干燥管，并配有有毒气体吸收装置（吸收液为5% NaOH溶液）。

在匀速搅拌下，从恒压滴液漏斗中缓慢滴加乙酸酐。调节滴加速度，使反应温度保持在60℃以下。滴加过程中温度上升，有大量白色气体逸出，溶液颜色加深，滴加完毕后，溶液呈淡紫色胶黏。用油浴加热回流反应直至无HCl气体逸出，溶液变浅棕色。

撤去气体吸收装置并冷却烧瓶，将其置于冷水浴中，在搅拌下加入一定量的冰水混合物。固体物质全部溶解（若未完全溶解，可滴加少量浓盐酸）。将反应物转入分液漏斗中，分离有机层和水层。水层用甲苯分两次萃取后合并，再用5% NaOH溶液、蒸馏水分别洗涤至水层pH值等于7。

旋转蒸发除去甲苯及少量水分的混合物并回收溶剂，残余液体减压蒸馏收集25mmHg下125-126℃的馏分（常压下，2-氯-1-(3,4-二氟苯基)乙酮的沸点为245～247℃），最终得到棕色油状液体。

反应信息

• 作为反应物：
  描述：

  2-氯-1-(3,4-二氟苯基)乙酮 在 sodium hypochlorite 、 氯化亚砜 、 水 、 烟酰胺腺嘌呤双核苷酸磷酸盐 、 碳酸氢钠 、 sodium carbonate 、 CDX-023 、 sodium hydroxide 、 sodium t-butanolate 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 14.17h， 生成 替格瑞洛
  参考文献：
  名称：

  [EN] A METHOD FOR PREPARING (1S)-2-CHLORO-1-(3,4-DIFLUOROPHENYL) ETHANOL
  [FR] PROCÉDÉ DE PRÉPARATION DE (1S)-2-CHLORO-1-(3,4-DIFLUOROPHÉNYL)ÉTHANOL

  摘要：

  The invention relates to a process for preparation of compound of formula (I) by reacting 2-chloro-1-(3,4-difluorophenyl)ethanone of formula (II) in a buffer and in the presence of an enzymeCDX-023and co-enzyme NADP.

  公开号：

  WO2023223335A1
• 作为产物：
  描述：

  1,2-二氟苯 以96%的产率得到
  参考文献：
  名称：

  BERCHER H.; EHLERS D.; GRISK A., PHARMAZIE , 1976, 31, NO 6, 351-354;

  摘要：

  DOI：

文献信息

• [EN] METALLOENZYME INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE MÉTALLOENZYMES
  申请人：VPS 3 INC

  公开号：WO2018165520A1

  公开（公告）日：2018-09-13

  Provided are compounds having HDAC6 modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by HDAC6.

  提供具有HDAC6调节活性的化合物，以及通过HDAC6介导的治疗疾病、疾病或症状的方法。
• Direct Synthesis of 3-Acylindoles through Rhodium(III)-Catalyzed Annulation of<i>N</i>-Phenylamidines with α-Cl Ketones
  作者：Jianhui Zhou、Jian Li、Yazhou Li、Chenglin Wu、Guoxue He、Qiaolan Yang、Yu Zhou、Hong Liu

  DOI：10.1021/acs.orglett.8b03383

  日期：2018.12.7

  versatile 3-acylindoles through Rh(III)-catalyzed C–H activation and annulation cascade of N-phenylamidines with α-Cl ketones was developed, in which α-Cl ketones serve as unusual one-carbon (sp3) synthons. This strategy features high regioselectivity, efficiency, wide substrate tolerance, and mild reaction conditions, which further underscore its synthetic utility in drug molecule synthesis.

  在本研究中，开发了一种新的合成策略，可通过Rh（III）催化的C–H活化和N-苯基am与α-Cl酮的环合级联反应直接生产通用的3-acylindoles ，其中α-Cl酮用作不寻常的一碳（sp 3）合成子。该策略具有较高的区域选择性，效率，宽的底物耐受性和温和的反应条件，这进一步强调了其在药物分子合成中的合成效用。
• Indol-3-yl-carbonyl-spiro-piperidine derivatives as Vla receptor antagonists
  申请人：Bissantz Caterina

  公开号：US20070027173A1

  公开（公告）日：2007-02-01

  The invention relates to indol-3-yl-carbonyl-spiro-piperidine derivatives which act as V1a receptor antagonists and which are represented by Formula I: wherein the spiro-piperidine head group A and the residues R 1 , R 2 and R 3 are as defined herein. The invention further relates to pharmaceutical compositions containing such compounds, methods for preparing the compounds and pharmaceutical compositions, and their use in the treatment of dysmenorrhea, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, obsessive compulsive disorder, anxious and depressive disorders.

  本发明涉及作为V1a受体拮抗剂的吲哚-3-基-甲酰基-螺环-哌啶衍生物，其由公式I表示：其中，螺环-哌啶头基A以及残基R1、R2和R3如本文所述定义。本发明进一步涉及含有此类化合物的药物组合物，制备化合物和药物组合物的方法，以及它们在治疗痛经、高血压、慢性心力衰竭、血管升压素不适当分泌、肝硬化、肾病综合征、强迫症、焦虑和抑郁障碍中的用途。
• NOVEL PROCESSES FOR THE PREPARATION OF PHENYLCYCLOPROPYLAMINE DERIVATIVES AND USE THEREOF FOR PREPARING TICAGRELOR
  申请人：Khile Anil Shahaji

  公开号：US20130165696A1

  公开（公告）日：2013-06-27

  Provided herein are novel processes for the preparation of phenylcyclopropylamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of a substantially pure ticagrelor intermediate, trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. Provided further herein are novel acid addition salts of trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine, and process for their preparation. The intermediate and its acid addition salts are useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity.

  本文提供了一种制备苯基环丙胺衍生物的新型工艺，这些衍生物在三唑并[4,5-d]嘧啶化合物的制备中是有用的中间体。特别提供了一种新颖、商业可行且在工业上具有优势的工艺，用于制备一种基本纯的替卡格雷中间体，即trans-(1R,2S)-2-(3,4-二氟苯基)-环丙胺。此外，本文还提供了trans-(1R,2S)-2-(3,4-二氟苯基)-环丙胺的新型酸加盐，以及其制备工艺。该中间体及其酸加盐对于高产率和纯度制备替卡格雷或其药用可接受盐是有用的。
• [EN] SYNTHESIS OF 2-(3,4-DIFLUOROPHENYL)CYCLOPROPANAMINE DERIVATIVES AND SALTS<br/>[FR] SYNTHÈSE DE DÉRIVÉS DE LA 2-(3,4-DIFLUOROPHÉNYL)CYCLOPROPANAMINE ET DE SELS DE CELLE-CI
  申请人：SANDOZ AG

  公开号：WO2013144295A1

  公开（公告）日：2013-10-03

  The present invention relates to the field of organic synthesis and describes the synthesis of specific intermediates suitable for the preparation of triazolopyrimidine compounds such as ticagrelor.

  本发明涉及有机合成领域，并描述了适用于制备三唑吡咯嘧啶类化合物（如替卡格雷）的特定中间体的合成。