1-BOC-哌啶-3-羧酸 | 163438-09-3

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - BOC-氨基酸
• 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-BOC-哌啶-3-羧酸
• 英文名称: BOC-nipecotic acid
• 英文别名: N-(tert-butyloxycarbonyl)nipecotic acid；1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid；1-(tert-butoxycarbonyl)-3-piperidinecarboxylic acid；(±)-N-Boc-nipecotic acid；1-Boc-piperidine-3-carboxylic acid；1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid
• CAS: 163438-09-3；71381-75-4；84358-12-3
• 化学式: C₁₁H₁₉NO₄
• mdl: MFCD00673775
• 分子量: 229.276
• InChiKey: NXILIHONWRXHFA-UHFFFAOYSA-N

物化性质

• 熔点：
  159-162 °C(lit.)
• 沸点：
  353.2±35.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)
• 稳定性/保质期：
  常温常压下稳定，避免与强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.818
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933399090
• 危险品运输编号：
  NONH for all modes of transport
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338
• 储存条件：
  常温下应存放在密封容器中，并避免光照。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
(R)-1-Boc-piperidine-3-carboxylic acid
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
(R)-1-Boc-piperidine-3-carboxylic acid
Ingredient name:
CAS number: 163438-09-3

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C11H19NO4
Molecular weight: 229.3

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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, nitrogen oxides.

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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

概述

N-Boc-3-哌啶甲酸是一种有机中间体，可通过哌啶-3-羧酸进行Boc保护而得到。

合成方法

将哌啶-3-羧酸（1.29g，10mmol）溶解在THF（20mL）中，加入4N氢氧化钠水溶液（5mL），再加入二碳酸二叔丁酯（2.62g，12mmol）。反应混合物搅拌6小时后，用3NHCl（7mL）酸化，并用乙酸乙酯萃取三次。用水（2X）和盐水洗涤合并的有机萃取物，然后干燥、过滤并真空浓缩，最终得到白色固体N-Boc-3-哌啶甲酸，产率为2.11g。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  N-Boc-3-哌啶甲酸乙酯	ethyl N-(t-butyloxycarbonyl)nipecotate	130250-54-3	C13H23NO4	257.33
  1-Boc-3-羟甲基哌啶	tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate	116574-71-1	C11H21NO3	215.293
  1-Boc-3-羟甲基吡咯烷	tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate	114214-69-6	C10H19NO3	201.266

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  N-Boc-3-哌啶甲酸甲酯	1-tert-butyl 3-methyl piperidine-1,3-dicarboxylate	148763-41-1	C12H21NO4	243.303
  ——	piperidine-1,3-dicarboxylic acid 3-allyl ester 1-tert-butyl ester	1263773-92-7	C14H23NO4	269.341
  ——	piperidine-1,3-dicarboxylic acid 3-((E)-but-2-enyl)ester 1-tert-butyl ester	1263773-82-5	C15H25NO4	283.368
  ——	piperidine-1,3-dicarboxylic acid 3-((E)-but-2-enyl) ester 1-tert-butyl ester	1263773-70-1	C15H25NO4	283.368
  1-Boc-哌啶-3-甲醛	3-formylpiperidine-1-carboxylic acid tert-butyl ester	118156-93-7	C11H19NO3	213.277
  N-Boc-3-甲基-3-哌啶甲酸甲酯	1-tert-butyl 3-methyl 3-methylpiperidine-1,3-dicarboxylate	888952-55-4	C13H23NO4	257.33
  1-Boc-3-羟甲基哌啶	tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate	116574-71-1	C11H21NO3	215.293
  ——	piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-(3,3-difluoro-allyl) ester	1263774-17-9	C14H21F2NO4	305.322
  3-(2-丙基)-1,3-哌啶二羧酸-1-(1,1-二甲基乙基)酯	3-allylpiperidine-1,3-dicarboxylic acid 1-tert-butyl ester	959236-11-4	C14H23NO4	269.341
  3-乙酰基哌啶-1-羧酸叔丁酯	tert-butyl 3-acetylpiperidine-1-carboxylate	858643-92-2	C12H21NO3	227.304

反应信息

• 作为反应物：
  描述：

  1-BOC-哌啶-3-羧酸 在 palladium on activated charcoal lithium aluminium tetrahydride 、 ammonium acetate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， -15.0~150.0 ℃ 、303.98 kPa 条件下， 反应 38.5h， 生成 tert-butyl 3-[2-amino-3-cyano-6-(2-hydroxyphenyl)-4-pyridinyl]-1-piperidinecarboxylate
  参考文献：
  名称：

  新型IKK-β抑制剂的合成与构效关系。第2部分：提高体外活性。

  摘要：

  合成了一系列的2-氨基-3-氰基-4-烷基-6-（2-羟基苯基）吡啶衍生物，并将其评估为IkappaB激酶β（IKK-β）抑制剂。氨基吡啶基团取代核心吡啶环上4位的芳香族基团导致激酶酶和细胞效能的显着增加，并提供了具有低于100 nM的IC（50）值的强效IKK-β抑制剂。

  DOI：

  10.1016/j.bmcl.2004.05.040
• 作为产物：
  描述：

  3-哌啶甲酸乙酯 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 1-BOC-哌啶-3-羧酸
  参考文献：
  名称：

  新型杂环螺3-（N-甲基-N-苯基氨基）-2 H-叠氮基的合成及其作为氨基酸等价物在模型三肽制备中的应用

  摘要：

  描述了基于酰胺烯酸酯和二氯代氯代磷酸酯之间反应的新型杂环基3-氨基-2H-叠氮基的合成。已经表明该化合物是有用的氨基酸当量，并且以良好的总产率实现了模型三肽的合成。

  DOI：

  10.1016/s0040-4020(01)87199-4

文献信息

• 크로만 유도체 및 이를 유효성분으로 함유하는 신생혈관성 안질환 또는 암의 예방 또는 치료용 약학적 조성물
  申请人：Gachon University of Industry-Academic cooperation Foundation 가천대학교 산학협력단(220040376324) BRN ▼129-82-07687

  公开号：KR20200124630A

  公开（公告）日：2020-11-03

  본 발명은 크로만 유도체인 하기 화학식 1의 화합물, 이의 수화물, 이의 입체 이성질체, 또는 이의 약학적으로 허용 가능한 염을 포함하는 암 또는 신생혈관과 관련된 질환 치료용 약학적 조성물을 제공한다. [화학식 1] (상기 화학식 1에서 R, R, R, R, R, R, R은 발명의 설명에서 정의한 바와 같다.)

  本发明提供了一种用于治疗与癌症或新生血管有关的疾病的药学组合物，其中包括化学式1的某种克隆衍生物化合物、其水合物、其立体异构体或其药学上可接受的盐。【化学式1】（其中R，R，R，R，R，R，R如上述化学式1中所定义）。
• MACROCYCLIC COMPOUNDS AND THEIR USE AS KINASE INHIBITORS
  申请人：Combs Andrew Paul

  公开号：US20090286778A1

  公开（公告）日：2009-11-19

  The present invention relates to macrocyclic compounds of Formula I: or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK/ALK inhibitors useful in the treatment of JAK/ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

  本发明涉及以下化学式I的大环化合物： 或其药用可接受盐或季铵盐，其中所述成员在此提供，并且它们的组成物和使用方法，这些JAK/ALK抑制剂在治疗JAK/ALK相关疾病中有用，例如炎症和自身免疫性疾病以及癌症。
• Carbonic anhydrase activators: amino acyl/dipeptidyl histamine derivatives bind with high affinity to isozymes I, II and IV and act as efficient activators
  作者：Claudiu T. Supuran、Andrea Scozzafava

  DOI：10.1016/s0968-0896(99)00227-8

  日期：1999.12

  a series of compounds with the general formula AA-Hst (AA = amino acyl; dipeptidyl). The new derivatives were assayed as activators of three carbonic anhydrase (CA) isozymes, hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound form). Efficient activation was observed against all three isozymes, but especially against hCA I and bCA IV, with affinities in the nanomolar range for the best compounds

  组胺（Hst）与四溴邻苯二甲酸酐反应，并用三苯甲基磺酰氯保护其咪唑部分，然后进行肼解反应，得到N-1-三苯甲基磺酰-组胺，这是一种关键中间体，在其氨基乙基部分被进一步衍生。在咪唑类和氨基部分脱保护后，在碳二亚胺存在下，关键中间体与N-Boc-氨基酸/二肽（Boc-AA）反应，得到了一系列通式为AA-Hst的化合物（AA =氨基酰基；二肽基）。分析了新衍生物作为三种碳酸酐酶（CA）同工酶的激活剂，它们分别是hCA I，hCA II（胞质形式）和bCA IV（膜结合形式）。观察到针对所有三种同工酶的有效活化，尤其是针对hCA I和bCA IV的活化，其最佳化合物的亲和力在纳摩尔范围内。另一方面，hCA II可以被约10-20 nM的亲和力激活。这类新型的CA激活剂可能导致针对CA缺乏综合症（一种骨骼，脑和肾脏的遗传性疾病）的药物/诊断剂的开发。
• Generation and Cross-Coupling of Organozinc Reagents in Flow
  作者：Ananda Herath、Valentina Molteni、Shifeng Pan、Jon Loren

  DOI：10.1021/acs.orglett.8b03156

  日期：2018.12.7

  formation of organozinc reagents and subsequent cross-coupling with aryl halides and activated carboxylic acids is reported. Formation of organozinc reagents is achieved by pumping organic halides, in the presence of ZnCl2 and LiCl, through an activated Mg-packed column under flow conditions. This method provides efficient in situ formation of aryl, primary, secondary, and tertiary alkyl organozinc reagents

  报道了一种通用的流动合成方法，用于原位形成有机锌试剂，然后与芳基卤化物和活化的羧酸进行交叉偶联。有机锌试剂的形成是通过在流动条件下将有机卤化物在ZnCl 2和LiCl的存在下泵送通过活化的Mg填充柱来实现的。该方法可有效地原位形成芳基，伯，仲和叔烷基有机锌试剂，随后将其在下游进行Negishi或脱羧Negishi交叉偶联反应的伸缩。所描述的方法提供了使用有机锌试剂获得各种C–C键的方法，这些试剂否则在商业上是不可用的，或者在传统的间歇反应条件下难以制备。
• Visible-Light-Mediated Alkylation of Thiophenols via Electron Donor–Acceptor Complexes Formed between Two Reactants
  作者：Yi-Ping Cai、Fang-Yuan Nie、Qin-Hua Song

  DOI：10.1021/acs.joc.1c01433

  日期：2021.9.3

  A metal-free, photocatalyst-free, photochemical system was developed for the direct alkylation of thiophenols via electron donor–acceptor (EDA) complexes (KEDA = 145 M–1) between two reactants, N-hydroxyphthalimide esters as acceptors and thiophenol anions as donors, in the presence of a tertiary amine. The EDA complexes in the reaction system have a broad range of visible-light absorption (400–650

  开发了一种无金属、无光催化剂的光化学系统，用于通过两种反应物之间的电子供体 - 受体 (EDA) 配合物 ( K EDA = 145 M –1 )直接烷基化苯硫酚，N-羟基邻苯二甲酰亚胺酯作为受体和苯硫酚阴离子作为供体，在叔胺的存在下。反应体系中的 EDA 配合物具有广泛的可见光吸收范围（400-650 nm），可以在阳光下有效触发反应。

表征谱图