3-氟-4-甲基苯酚 | 452-78-8

• 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 - 苯类化合物 - 酚类
• 中文名称: 3-氟-4-甲基苯酚
• 中文别名: 3-氟对甲酚；2-氟-4-羟基甲苯；3-氟对甲基苯酚
• 英文名称: 3-fluoro-4-methyl phenol
• 英文别名: 3-fluoro-p-cresol；3-Fluoro-4-methylphenol
• CAS: 452-78-8
• 化学式: C₇H₇FO
• mdl: MFCD00143164
• 分子量: 126.13
• InChiKey: GJOOCAXPERKNMN-UHFFFAOYSA-N

物化性质

• 熔点：
  72 °C
• 沸点：
  196 °C
• 密度：
  1.17
• 闪点：
  29 °C
• 稳定性/保质期：

  按规格使用和贮存，不会发生分解，避免与氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  8
• 危险品标志：
  Xi
• 危险类别码：
  R21/22
• 危险品运输编号：
  2922
• 海关编码：
  2908199090
• 安全说明：
  S26,S36/37/39
• 危险性防范说明：
  P273,P305+P351+P338
• 危险性描述：
  H302,H319,H412
• 储存条件：
  密封保存，置于通风干燥处，并远离其他氧化物。

SDS

3-Fluoro-p-cresol Revision number: 5
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: 3-Fluoro-p-cresol

Revision number: 5

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Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
HEALTH HAZARDS
Acute toxicity (Oral) Category 4
Category 4
Acute toxicity (Dermal)
Acute toxicity (Inhalation) Category 4
Category 2
Skin corrosion/irritation
Serious eye damage/eye irritation Category 2A
Not classified
ENVIRONMENTAL HAZARDS
GHS label elements, including precautionary statements
Pictograms or hazard symbols
Signal word Warning
Harmful if swallowed, in contact with skin or if inhaled
Hazard statements
Causes skin irritation
Causes serious eye irritation
Precautionary statements:
Avoid breathing dust/fume/gas/mist/vapours/spray.
[Prevention]
Use only outdoors or in a well-ventilated area.
Do not eat, drink or smoke when using this product.
Wash hands thoroughly after handling.
Wear protective gloves and eye/face protection.
[Response] IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for
breathing. Call a POISON CENTER or doctor/physician if you feel unwell.
IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell.
Rinse mouth.
IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses,
if present and easy to do. Continue rinsing.
If eye irritation persists: Get medical advice/attention.
IF ON SKIN: Gently wash with plenty of soap and water.
If skin irritation occurs: Get medical advice/attention.
Wash contaminated clothing before reuse.
Call a POISON CENTER or doctor/physician if you feel unwell.
3-Fluoro-p-cresol

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Section 2. HAZARDS IDENTIFICATION
[Disposal] Dispose of contents/container through a waste management company authorized by
the local government.

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
Components: 3-Fluoro-p-cresol
>98.0%(GC)
Percent:
CAS Number: 452-78-8
3-Fluoro-4-methylphenol
Synonyms:
Chemical Formula: C7H7FO

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Section 4. FIRST AID MEASURES
Inhalation: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Call a POISON CENTER or doctor/physician if you feel unwell.
Skin contact: Remove/Take off immediately all contaminated clothing. Gently wash with plenty of
soap and water. If skin irritation or rash occurs: Get medical advice/attention.
Eye contact: Rinse cautiously with water for several minutes. Remove contact lenses, if present
and easy to do. Continue rinsing. If eye irritation persists: Get medical
advice/attention.
Call a POISON CENTER or doctor/physician if you feel unwell. Rinse mouth.
Ingestion:
Protection of first-aiders: A rescuer should wear personal protective equipment, such as rubber gloves and air-
tight goggles.

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Section 5. FIRE-FIGHTING MEASURES
Dry chemical, foam, water spray, carbon dioxide.
Suitable extinguishing
media:
Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to
from the chemical: generate poisonous fume.
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
When extinguishing fire, be sure to wear personal protective equipment.
Special protective
equipment for firefighters:

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, Use personal protective equipment. Keep people away from and upwind of spill/leak.
protective equipment and Entry to non-involved personnel should be controlled around the leakage area by
emergency procedures: roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Technical measures: Handling is performed in a well ventilated place. Wear suitable protective equipment.
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a local exhaust if dust or aerosol will be generated.
Advice on safe handling: Avoid contact with skin, eyes and clothing.
Conditions for safe storage, including any
incompatibilities
Storage conditions: Keep container tightly closed. Store in a cool and dark place.
Store under inert gas.
Store away from incompatible materials such as oxidizing agents.
Air-sensitive
3-Fluoro-p-cresol

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Section 7. HANDLING AND STORAGE
Packaging material: Comply with laws.

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Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Engineering controls: Install a closed system or local exhaust as possible so that workers should not be
exposed directly. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator. Follow local and national regulations.
Hand protection: Protective gloves.
Eye protection: Safety glasses. A face-shield, if the situation requires.
Skin and body protection: Protective clothing. Protective boots, if the situation requires.

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Solid
Physical state (20°C):
Form: Crystal- Lump
Colour: White - Pale reddish yellow
Odour: No data available
pH: No data available
Melting point/freezing point:29°C (Freezing point)
Boiling point/range: 196°C
Flash point: No data available
Flammability or explosive
limits:
Lower: No data available
No data available
Upper:
Relative density: 1.17
Solubility(ies):
[Water] No data available
[Other solvents] No data available

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Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide, Hydrogen fluoride
products:

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Section 11. TOXICOLOGICAL INFORMATION
Acute Toxicity: No data available
Skin corrosion/irritation: No data available
Serious eye No data available
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
IARC = No data available
NTP = No data available
Reproductive toxicity: No data available

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Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
No data available
Fish:
Crustacea: No data available
No data available
Algae:
Persistence / degradability: No data available
No data available
Bioaccumulative
potential(BCF):
3-Fluoro-p-cresol

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Section 12. ECOLOGICAL INFORMATION
Mobility in soil
No data available
Log Pow:
Soil adsorption (Koc): No data available
No data available
Henry's Law
constant(PaM3/mol):

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Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system.
Observe all federal, state and local regulations when disposing of the substance.

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Section 14. TRANSPORT INFORMATION
Does not correspond to the classification standard of the United Nations
Hazards Class:
UN-No: Not listed

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Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用 3-氟-4-甲基苯酚可用作有机合成中间体和医药中间体，主要用于实验室研发过程和化工生产过程中。

制备 将5-甲氧基-2-甲基苯胺（5.0g，36mmol）、盐酸（7.6mL的12M溶液，91mmol）和水（11mL）的混合物在60℃加热15分钟直至完全溶解。将反应混合物冷却至0℃，逐滴加入NaNO₂（2.5g，36mmol）水溶液（内温≤7℃）。将反应混合物在0℃搅拌30分钟，小心地加入HBF₄的0℃溶液（5.3mL的48％溶液，40mmol）。在0℃搅拌反应混合物20分钟，滤出形成的棕色固体，用冰水（3×10mL）和水（2×10mL）洗涤。将固体在高真空下干燥20小时，然后加热至停止放出BF₃（白色烟雾），直至反应完全。将得到的棕色油状物分配在乙酸乙酯和水中。将有机相干燥（Na₂SO₄），减压浓缩后用Kugelrohr球管蒸馏器蒸馏，得到3-氟-4-甲基苯甲醚（1.6g，产率31%），为无色油状物。

向3-氟-4-甲基苯甲醚（1.62g，11.6mmol）在CH₂Cl₂（10mL）中的-70℃溶液逐滴加入BBr₃（10mL，12mmol）。将反应混合物在-70℃搅拌10分钟，然后温热至0℃并在0℃下搅拌2小时。再将其温热至室温，减压浓缩后，残余物分配在水中和EtOAc中。有机相用水洗，用Na₂SO₄干燥，再次减压浓缩得到3-氟-4-甲基苯酚（1.1g，产率75%），为油状物。

化学性质： 淡黄色油状液体

反应信息

• 作为反应物：
  描述：

  3-氟-4-甲基苯酚 在 苄基三乙基氯化铵 、 硝酸 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 5-氟-4-甲基-2-硝基苯甲醚
  参考文献：
  名称：

  EGFR抑制剂2-苯氨基嘧啶衍生物的设计、合成及生物学评价

  摘要：

   [显示省略]

  DOI：

  10.1016/j.bmcl.2024.129648
• 作为产物：
  描述：

  3-氟-4-甲基苯胺 在 tetrafluoroboric acid 、 sodium nitrite 作用下， 生成 3-氟-4-甲基苯酚
  参考文献：
  名称：

  Brown et al., Journal of the Chemical Society, 1949, p. Spl. 113

  摘要：

  DOI：

文献信息

• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：PFIZER

  公开号：WO2014068527A1

  公开（公告）日：2014-05-08

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

  本文披露了一种与Bruton's酪氨酸激酶（BTK）形成共价键的化合物。公开了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。公开了使用BTK抑制剂的方法，单独或与其他治疗剂联合治疗自身免疫疾病或症状、异源免疫疾病或症状、癌症，包括淋巴瘤，以及炎症性疾病或症状的方法。 (化学式I)
• Substituted N, N-disubstituted diamino compounds useful for inhibiting cholesteryl ester transfer protein activity
  申请人：——

  公开号：US20020120011A1

  公开（公告）日：2002-08-29

  The invention relates to substituted polycyclic aryl and heteroaryl tertiary-heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Preferred tertiary-heteroalkylamine compounds are substituted N,N-disubstituted diamines. A preferred specific N,N-disubstituted diamine is the compound: 1

  这项发明涉及替代多环芳基和杂环芳基的三级杂烷基胺化合物，可用作胆固醇酯转移蛋白（CETP；血浆脂质转移蛋白-I）的抑制剂，以及用于治疗动脉粥样硬化和其他冠状动脉疾病的化合物、组合物和方法。首选的三级杂烷基胺化合物是取代的N,N-二取代二胺。首选的具体N,N-二取代二胺化合物是：1
• Visible Light-Induced Borylation of C–O, C–N, and C–X Bonds
  作者：Shengfei Jin、Hang. T. Dang、Graham C. Haug、Ru He、Viet D. Nguyen、Vu T. Nguyen、Hadi D. Arman、Kirk S. Schanze、Oleg V. Larionov

  DOI：10.1021/jacs.9b12519

  日期：2020.1.22

  photocatalytic borylation method that can effect borylation of a wide range of substrates, including strong C‒O bonds, remains elusive. Herein, we report a general, metal-free visible light-induced photocatalytic borylation platform that enables borylation of electron rich derivatives of phenols and anilines, chloroarenes, as well as other haloarenes. The reac-tion exhibits excellent functional group

  硼酸是中心重要的功能基序和合成前体。可见光诱导的硼酸化可以提供结构多样化的硼酸盐，但一种广泛有效的光催化硼酸化方法可以影响包括强 C-O 键在内的多种底物的硼化，仍然难以实现。在此，我们报告了一种通用的、无金属的可见光诱导光催化硼化平台，该平台能够对苯酚和苯胺、氯芳烃以及其他卤代芳烃的富电子衍生物进行硼化。该反应表现出优异的官能团耐受性，正如一系列结构复杂底物的硼化反应所证明的那样。值得注意的是，该反应是由吩噻嗪催化的，这是一种简单的有机光催化剂，MW< 200通过质子耦合电子转移机制介导了以前无法实现的可见光诱导的苯酚衍生物单电子还原，还原电位为~-3 V vs SCE。机理研究指出了光催化剂-碱相互作用的关键作用。
• PYRROLOPYRAZINE-SPIROCYCLIC PIPERIDINE AMIDES AS MODULATORS OF ION CHANNELS
  申请人：Hadida Ruah Sara Sabina

  公开号：US20120196869A1

  公开（公告）日：2012-08-02

  The invention relates to pyrrolopyrazine-spirocyclic piperidine amide compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  这项发明涉及对离子通道具有抑制作用的吡咯吡嘧啶-螺环哌啶酰胺化合物。该发明还提供了包括该发明化合物的药学上可接受的组合物，以及使用这些组合物治疗各种疾病的方法。
• Discovery of DS-6930, a potent selective PPARγ modulator. Part II: Lead optimization
  作者：Tsuyoshi Shinozuka、Tomoharu Tsukada、Kunihiko Fujii、Eri Tokumaru、Kousei Shimada、Yoshiyuki Onishi、Yumi Matsui、Satoko Wakimoto、Masanori Kuroha、Tsuneaki Ogata、Kazushi Araki、Jun Ohsumi、Ryoko Sawamura、Nobuaki Watanabe、Hideki Yamamoto、Kazunori Fujimoto、Yoshiro Tani、Makoto Mori、Jun Tanaka

  DOI：10.1016/j.bmc.2018.09.005

  日期：2018.10

  synthesized compound (II) for the avoidance of hepatotoxicity. The replacement of the left-hand side benzene with 2-pyridine resulted in the substantial loss of potency. Because poor membrane permeability was responsible for poor potency in vitro, the adjustment of lipophilicity was examined, which resulted in the discovery of dimethyl pyridine derivative (I, DS-6930). In preclinical studies, DS-6930 demonstrated

  为了避免肝毒性，尝试降低先前合成的化合物（II）的亲脂性。用2-吡啶代替左手侧苯导致效力的实质损失。由于差的膜通透性导致体外效价差，因此对亲脂性的调节进行了检查，从而发现了二甲基吡啶衍生物（I，DS-6930）。在临床前研究中，DS-6930表现出较高的PPARγ激动剂效价，且血浆葡萄糖降低明显。DS-6930在体内进行毒理学评估后维持与PPARγ相关的副作用减少，并没有显示出肝毒性。辅助因子募集测定表明，显着募集了一些辅助因子，例如RIP140和PGC1，而几个典型因子并未受到影响。这种选择性辅因子募集是由于DS-6930的独特结合模式引起的。钙盐DS-6930b被认为是有效的胰岛素增敏剂，无水肿，可在T2DM患者中进行临床评估。