4-(2-(苄基(叔丁基)氨基)-1-羟基乙基)-2-(羟甲基)苯酚 | 24085-03-8

• 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 - 苯和取代衍生物
• 中文名称: 4-(2-(苄基(叔丁基)氨基)-1-羟基乙基)-2-(羟甲基)苯酚
• 英文名称: α-[(benzyl-tert-butylamino)methyl]-m-xylene-4,α,α'-triol
• 英文别名: α¹-Benzyl-tert-butylaminomethyl-4-hydroxy-m-xylol-α¹,α³-diol；N-Benzyl albuterol；4-[2-[benzyl(tert-butyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol
• CAS: 24085-03-8
• 化学式: C₂₀H₂₇NO₃
• 分子量: 329.439
• InChiKey: NZBXAYHLQSMNQS-UHFFFAOYSA-N

物化性质

• 沸点：
  496.0±33.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)
• LogP：
  2.79

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2922509090
• WGK Germany：
  3

SDS

Name:	1-(4-Hydroxy-3-hydroxymethylphenyl)-2-(tert-butylbenzylamino)ethanol Material Safety Data Sheet
Synonym:
CAS:	24085-03-8

Section 1 - Chemical Product MSDS Name:1-(4-Hydroxy-3-hydroxymethylphenyl)-2-(tert-butylbenzylamino)ethanol Material Safety Data Sheet
Synonym:

---

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
24085-03-8	1-(4-Hydroxy-3-hydroxymethylphenyl)-2-		246-013-7

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

---

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.

---

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.

---

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.

---

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.

---

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.

---

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# 24085-03-8: 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.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Crystalline powder
Color: white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 114 - 118 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C20H27NO3
Molecular Weight: 329.44

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Will not occur.

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 24085-03-8 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
1-(4-Hydroxy-3-hydroxymethylphenyl)-2-(tert-butylbenzylamino)ethanol - Not listed by ACGIH, IARC, or NTP.

---

Section 12 - ECOLOGICAL INFORMATION

---

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

---

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.

---

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# 24085-03-8: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 24085-03-8 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 24085-03-8 is not listed on the TSCA inventory.
It is for research and development use only.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

应用广泛，4-(2-(苄基(叔丁基)氨基)-1-羟基乙基)-2-(羟甲基)苯酚不仅可用作有机合成中间体，还可作为医药中间体。它主要应用于实验室的研发过程以及化工生产的各个环节中。

反应信息

• 作为反应物：
  描述：

  4-(2-(苄基(叔丁基)氨基)-1-羟基乙基)-2-(羟甲基)苯酚 在 氢气 、 镍 作用下， 以 异丙醇 为溶剂， 60.0 ℃ 、413.68 kPa 条件下， 以90%的产率得到沙丁胺醇
  参考文献：
  名称：

  雷尼镍/异丙醇的新应用：减少有机化合物的高效系统

  摘要：

  摘要 在温和的温度和压力条件下，在异丙醇中用阮内镍催化加氢各种有机底物。与其他催化剂系统的比较证明了雷尼镍/异丙醇的优越性。

  DOI：

  10.1080/00397919708004201
• 作为产物：
  描述：

  N-苄基沙丁胺醇盐酸盐 在 sodium hydroxide 、 sodium tetrahydroborate 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 以81%的产率得到4-(2-(苄基(叔丁基)氨基)-1-羟基乙基)-2-(羟甲基)苯酚
  参考文献：
  名称：

  高通量筛选和反应分析相结合的方法来开发串联催化加氢合成沙丁胺醇

  摘要：

  描述了一种高通量筛选和反应谱分析相结合的方法，用于缩合成沙丁胺醇的两种还原反应。优化研究显示了弱酸性条件的有益作用，以及使用水作为助溶剂。使用Pd / C催化剂持续形成脱氧杂质导致了反应谱研究的开始，该研究表明快速脱苄基后形成的酮中间体是脱氧杂质的唯一来源，这表明更快速的酮氢化应将这种脱氧减至最小。已经开发出了基于这些见解的双重催化剂方法，与仅含钯的系统相比，钯/铂和钌/铂催化剂系统具有更高的选择性。基于表明脱氧副反应在脱苄基酮中间体的浓度中是一级反应的反应曲线，将用于快速和选择性酮氢化的Pt催化剂与已知进行选择性脱苄基的Pd和Ru催化剂配对。这些双重催化剂工艺的优化导致了重结晶后以20 g规模证明以49％分离产率制备沙丁胺醇的条件。

  DOI：

  10.1021/acs.oprd.7b00261

文献信息

• 一种沙丁胺醇杂质化合物及其制备方法、检测方法和用途
  申请人：仁合诚益医药技术（天津）有限公司

  公开号：CN112920064A

  公开（公告）日：2021-06-08

  本发明公开了一种沙丁胺醇杂质化合物及其制备方法、检测方法和用途，属于医药技术领域，沙丁胺醇杂质化合物是由沙丁胺醇分子结构中的酚羟基发生烷基取代反应而产生的，本发明首次公开了一种沙丁胺醇杂质化合物及其制备方法，弥补了目前制备该杂质方法的空缺，并且制备方法操作简单，后处理方便，并且制备出的沙丁胺醇杂质纯度高。
• 一种硫酸沙丁胺醇中间体的制备方法
  申请人：重庆康刻尔制药有限公司

  公开号：CN109761828A

  公开（公告）日：2019-05-17

  沙丁胺醇是一种β受体激动剂，目前沙丁胺醇的制备工艺，主要还是以原研工艺为主，原研工艺以对羟基苯乙酮为起始物料，经过氯甲基化，酯化，溴代，胺化，水解，还原制备得到沙丁胺醇。现有硫酸沙丁胺醇中间体的合成方法分多个步骤合成，操作繁琐，且制备过程中产物损失大，工艺时间较长。本发明一种硫酸沙丁胺醇中间体的制备方法是，化合物Ⅰ在还原剂的作用下还原羰基得到化合物Ⅱ，然后加入脱苄基试剂进行脱苄基反应得到硫酸沙丁胺醇中间体Ⅲ。本发明采用“一锅法”直接由化合物Ⅰ制备硫酸沙丁胺醇中间体Ⅲ，减少操作步骤，缩短了反应时间，提高了反应收率。
• Synthesis, Isolation and Characterization of Process-Related Impurities in Salbutamol Sulphate
  作者：Yogesh Kumar Sharma、Dau Dayal Agarwal、Sudesh Bhure、Rajendra Nath Mukharjee、Pramod Kumar Sahu、Santosh Bhardwaj

  DOI：10.1155/2011/230231

  日期：——

  Three known and one unknown impurities in salbutamol sulphate bulk drug at level 0.1% (ranging from 0.05-0.1%) were detected by gradient reverse phase high performance liquid chromatography. These impurities were preliminarily identified by the mass number of the impurities. Different experiments were conducted and finally synthesized and characterized the known and unknown imputities.

  通过梯度反相高效液相色谱法，在沙丁胺醇硫酸盐原料药中检测到三种已知和一种未知杂质，其含量为0.1%（范围为0.05-0.1%）。这些杂质通过其质量数进行初步鉴定。进行了不同的实验，最终合成和表征了已知和未知的杂质。
• 4 hydroxy-alpha'aminomethyl-m-xylene-alpha' alpha**3-diols
  申请人：ALLEN HANBURYS LIMITED

  公开号：US03644353A1

  公开（公告）日：1972-02-22

  1,200,886. Phenylaminoethanol derivatives. ALLEN &; HANBURYS Ltd. 15 Sept., 1967 [23 Sept., 1966; 21 April, 1967], Nos. 42590/66 and 18383/67. Heading C2C. Racemic and optically active compounds of the general formula (R 1 =H or C 1-6 alkyl; R 2 =H or PhCH 2 ; R 3 = H, C 1-6 alkyl optionally substituted by hydroxy amino or heterocyclic groups, or cycloalkyl, aralkyl or aroxyalkyl each optionally substituted; X = C 1-6 hydroxyalkyl, hydroxyar (C 1-6 alkyl), COOH, COO(C 1-6 alkyl), CONHOH, CONHNH 2 or CONR 5 R 6 in which R 5 , 6 =H, aralkyl or C 1-6 alkyl optionally substituted by hydroxyl or amino groups or NR 5 R 6 = heterocyclic group) and their acid addition salts are prepared by (a) reducing a compound of the formula (X, R 1 , 2 , 3 are as above or are convertible thereto), if desired with protection of the phenolic OH group, or (b) reacting a compound of the formula (Hal = halogen) or with R 2 R 3 NH, optionally followed by (i) esterification when X=COOH, (ii) conversion of a compound in which X = COO(C 1-6 alkyl) to a compound in which X = CH 2 OH, CONHOH, CONHNH 2 or CONR 5 R 6 , (iii) conversion of a compound in which X= halogen to an organometallic compound and reaction with an aldehyde or ketone, (iv) salt formation and/or (v) resolution. The preparation; of starting -materials for process (a) by standard methods is described. The compounds of the invention possess either stimulant or blocking, actions on #- adrenergic receptors, and may be administered in the form of pharmaceutical preparations containing them in association with a carrier.

  1,200,886. 苯胺乙醇衍生物。ALLEN＆HANBURYS有限公司。1967年9月15日[1966年9月23日；1967年4月21日]，编号42590/66和18383/67。C2C类。通式为(R1=H或C1-6烷基; R2=H或PhCH2; R3=H，C1-6烷基，可选地取代羟基，氨基或杂环基团，或环烷基，芳基烷基或芳基氧基烷基，每个可选地取代; X=C1-6羟基烷基，羟基ar（C1-6烷基），COOH，COO（C1-6烷基），CONHOH，CONHNH2或CONR5R6其中R5,6=H，芳基烷基或可选地取代羟基或氨基基团或NR5R6=杂环基）及其酸加成盐可通过（a）还原式（X，R1,2,3与上述相同或可转化为上述）的化合物，如有必要，保护酚羟基，或（b）与R2R3NH的化合物反应，可选地后跟（i）酯化当X=COOH时，（ii）将X=COO（C1-6烷基）的化合物转化为X=CH2OH，CONHOH，CONHNH2或CONR5R6的化合物，（iii）将X=卤素的化合物转化为有机金属化合物并与醛或酮反应，（iv）盐形成和/或（v）分辨率。所述方法的起始材料的制备通过标准方法进行。本发明的化合物具有对#-肾上腺素能受体的兴奋或阻断作用，并可以在药物制剂中与载体结合后给予。
• 一种沙丁胺醇中间体的制备方法
  申请人：上海方予健康医药科技有限公司

  公开号：CN115448847A

  公开（公告）日：2022-12-09

  本发明涉及一种沙丁胺醇中间体的制备方法，该方法的反应路线如下： 该方法包括如下步骤：(1)将化合物IV与含硼试剂在有机溶剂A中反应，以形成化合物V；(2)向步骤(1)得到的产物中加入水和有机溶剂B，搅拌，分层，有机相浓缩至干，得油状物；(3)向步骤(2)得到的产物中加入水和有机溶剂C，溶解后，调酸，然后调碱，分层得到有机相；(4)将步骤(3)得到的有机相，调酸，然后调碱，分层，干燥，浓缩后得到产品。本发明通过控制pH值就可以除去残留的硼元素，操作简便，易于控制。