(S)-(+)-(3,5-二氧-4-磷环烷[2,1-A | 252288-04-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: (S)-(+)-(3,5-二氧-4-磷环烷[2,1-A
• 中文别名: (S)-(+)-(3,5-二氧杂-4-磷杂环庚二烯并[2,1-a:3,4-a']二萘-4-基)二乙胺；3,4-A']4-二萘基)二乙基胺；(S)-(+)-(3,5-二氧杂-4-磷杂-环庚三烯并[2,1-a；3,4-a']二萘-4-基)二乙基胺；(S)-(+)-(3,5-二氧-4-磷环烷[2,1-a；3,4-a]4-二萘基)二乙基胺；
• 英文名称: (R)-(-)-(3,5-dioxa-4-phosphacyclohepta[2,1-a:3,4-a']dinaphthalen-4-yl)diethylamine
• 英文别名: N,N-diethyl-12,14-dioxa-13-phosphapentacyclo[13.8.0.02,11.03,8.018,23]tricosa-1(15),2(11),3,5,7,9,16,18,20,22-decaen-13-amine
• CAS: 252288-04-3
• 化学式: C₂₄H₂₂NO₂P
• 分子量: 387.418
• InChiKey: SQKCCVLITFBZPD-UHFFFAOYSA-N

物化性质

• 沸点：
  566.4±33.0 °C(Predicted)
• 稳定性/保质期：

  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

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Section 1: Product Identification
Chemical Name: (S)-(+)-(3,5-Dioxa-4-phospha-cyclohepta[2,1-a;3,4-a']dinaphthalen-4-yl)diethylamine, min. 97%
CAS Registry Number: 252288-04-3
Formula: C24H22NO2P
EINECS Number: none
Chemical Family: organophosphine ligand
Synonym: none

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Section 2: Composition and Information on Ingredients
Ingredient CAS Number Percent ACGIH (TWA) OSHA (PEL)
Title compound 252288-04-3 100% no data no data

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Section 3: Hazards Identification
Emergency Overview: Irritating to skin, eyes and respiratory tract.
Primary Routes of Exposure: Ingestion, inhalation
Eye Contact: Causes slight to mild irritation of the eyes.
Skin Contact: Causes slight to mild irritation of the skin.
Inhalation: Irritating to the nose, mucous membranes and respiratory tract.
Ingestion: No information available on the physiological effects of ingestion. May be harmful if swallowed.
Acute Health Affects: Irritating to skin, eyes and respiratory tract.
Chronic Health Affects: No information on long-term chronic effects.
NTP: No
IARC: No
OSHA: No

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SECTION 4: First Aid Measures
Immediately flush the eyes with copious amounts of water for at least 10-15 minutes. A victim may need
Eye Exposure:
assistance in keeping their eye lids open. Get immediate medical attention.
Wash the affected area with water. Remove contaminated clothes if necessary. Seek medical assistance if
Skin Exposure:
irritation persists.
Remove the victim to fresh air. Closely monitor the victim for signs of respiratory problems, such as difficulty
Inhalation:
in breathing, coughing, wheezing, or pain. In such cases seek immediate medical assistance.
Seek medical attention immediately. Keep the victim calm. Give the victim water (only if conscious). Induce
Ingestion:
vomiting only if directed by medical personnel.

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SECTION 5: Fire Fighting Measures
Flash Point: no data
Autoignition Temperature: no data
Explosion Limits: no data
Extinguishing Medium: carbon dioxide, dry powder or foam
If this product is involved in a fire, fire fighters should be equipped with a NIOSH approved positive pressure
Special Fire Fighting Procedures:
self-contained breathing apparatus and full protective clothing.
Hazardous Combustion and If involved in a fire this material may emit toxic organic fumes and vapors of phosphorus pentoxide.
Decomposion Products:
Unusual Fire or Explosion Hazards: No unusual fire or explosion hazards.

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SECTION 6: Accidental Release Measures
Spill and Leak Procedures: Small spills can be mixed with vermiculite or sodium carbonate and swept up.

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SECTION 7: Handling and Storage
Store in a tightly sealed container under an inert atmosphere of nitrogen or argon. Keep in a cool, dry, well
Handling and Storage:
ventilated place.

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SECTION 8: Exposure Controls and Personal Protection
Eye Protection: Always wear approved safety glasses when handling a chemical substance in the laboratory.
Skin Protection: Wear protective clothing and gloves.
Ventilation: Handle the material in an efficient fume hood.
If ventilation is not available a respirator should be worn. The use of respirators requires a Respirator
Respirator:
Protection Program to be in compliance with 29 CFR 1910.134.
Ventilation: Handle the material in an efficient fume hood.
Additional Protection: No additional protection required.

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SECTION 9: Physical and Chemical Properties
Color and Form: white powder
Molecular Weight: 387.41
Melting Point: no data
Boiling Point: no data
Vapor Pressure: no data
Specific Gravity: no data
Odor: not determined
Solubility in Water: insoluble

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SECTION 10: Stability and Reactivity
Stability: moisture sensitive
Hazardous Polymerization: no hazardous polymerization
Conditions to Avoid: none
Incompatibility: strong oxidizing agents
Decomposition Products: carbon monoxide, carbon dioxide, nitrogen and phosphorus oxides and organic fumes.

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SECTION 11: Toxicological Information
RTECS Data: No information available in the RTECS files.
Carcinogenic Effects: no data
Mutagenic Effects: no data
Tetratogenic Effects: no data

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SECTION 12: Ecological Information
Ecological Information: No information available

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SECTION 13: Disposal Considerations
Disposal: Dispose of according to local, state and federal regulations.

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SECTION 14: Transportation
Shipping Name (CFR): Non-hazardous
Hazard Class (CFR): NA
Additional Hazard Class (CFR): NA
Packaging Group (CFR): NA
UN ID Number (CFR): NA
Shipping Name (IATA): Non-hazardous
Hazard Class (IATA): NA
Additional Hazard Class (IATA): NA
Packaging Group (IATA): NA
UN ID Number (IATA): NA

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SECTION 15: Regulatory Information
TSCA: Not listed in the TSCA inventory
SARA (Title 313): Title compound not listed
Second Ingredient: none

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (S)-(+)-(3,5-二氧-4-磷环烷[2,1-A 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以98%的产率得到
  参考文献：
  名称：

  手性磷试剂的合成及其对苯乙酮N-苯基亚胺不对称硼烷还原反应的催化活性

  摘要：

  以 L-脯氨酸、D-樟脑、(+)- 或 (-)-1,1'-联萘-2,2'-二醇、(-)-α-苯乙胺为原料合成了 11 种手性三价或四价磷试剂，初步研究了它们作为催化剂在苯乙酮N-苯基亚胺不对称硼烷还原反应中的应用。N-苯基α-苯乙胺以良好的收率获得，具有低至中等的对映选择性。© 2003 Wiley Periodicals, Inc. 杂原子化学 14:546–550, 2003; 在线发表于 Wiley InterScience (www.interscience.wiley.com)。DOI 10.1002/hc.10190

  DOI：

  10.1002/hc.10190
• 作为产物：
  描述：

  (R)-1,1'-Bi-2-naphthol 在 三乙胺 、 三氯化磷 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成 (S)-(+)-(3,5-二氧-4-磷环烷[2,1-A
  参考文献：
  名称：

  通过使用单齿亚磷酰胺配体对有机三氟硼酸钾的高对映选择性共轭加成。

  摘要：

  描述了亚磷酰胺配体在不存在水的情况下在铑催化的有机三氟硼酸钾向各种烯酮的不对称共轭加成中的使用。已经通过使用高通量筛选方法对有效催化剂进行了系统的研究。最初，我们筛选了反应条件，催化剂前体和聚焦的配体库。在下一步中，我们使用了单齿配体组合方法，最后我们通过在机器人中进行并行合成（即时配体库）建立了96种不同的亚磷酰胺的文库，并在环己烯酮的乙烯基化（高达88％对映异构体）中对其进行了测试。过量的ee）和4-苯基-3-丁烯-2-一（最高ee的42％）。通过使用苯基三氟硼酸钾对环己烯酮的丙烯酸化，得到具有99％ee的3-苯基环己酮。

  DOI：

  10.1021/jo0487810
• 作为试剂：
  描述：

  2-环己烯-1-酮 、 3-甲氧基苯硼酸 在 bis(ethylene)rhodium acetylacetonate 氢氧化钾 、 (S)-(+)-(3,5-二氧-4-磷环烷[2,1-A 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.0h， 以84%的产率得到(R)-3-(3-methoxyphenyl)cyclohexanone
  参考文献：
  名称：

  铑-单齿亚磷酰胺配合物在碱基存在下催化芳基硼酸与烯酮的不对称共轭加成

  摘要：

  在基于 (R)-二元醇和二烷基胺的手性亚磷酰胺配体存在下，进行铑 (I) 催化的芳基硼酸与 α,β-不饱和羰基化合物的 1,4-加成反应。在碱如 KOH 和 Et 3 N 的存在下，反应显着加速，使反应在 50°C 下在 6 小时内完成。添加到 2-环己烯酮后实现了高达 99% 的对映选择性，尽管它们对 2-环戊烯酮 (79% ee)、2-环庚烯酮 (77% ee) 和无环烯酮 (31-43% ee) 效果较差。

  DOI：

  10.1055/s-2003-39315

文献信息

• [EN] SUBSTITUTED PHENYL CYCLOALKYL PYRROLIDINE (PIPERIDINE) SPIROLACTAMS AND AMIDES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] SPIROLACTAMES ET AMIDES DE PHÉNYLCYCLOALKYLPYRROLIDINE (PIPÉRIDINE) SUBSTITUÉS, LEUR PRÉPARATION ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI SA

  公开号：WO2011143150A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims respectively a series of substituted phenyl cycloalkyl pyrrolidine (piperidine) spirolactams and amides of formula (I) (Ia) and formula (Ib) as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted phenyl cycloalkyl pyrrolidine (piperidine) spirolactams and amides of formula (Ia) and (Ib), and intermediates therefor.

  本发明分别公开和声明了一系列取代苯基环烷基吡咯烷（哌啶）螺内酰胺和酰胺的化合物，其化学式如下（I）（Ia）和（Ib）。更具体地，本发明的化合物是H3受体调节剂，因此在治疗和/或预防包括与中枢神经系统相关的多种疾病在内的由H3受体调节的疾病中特别有用。此外，本发明还公开了取代苯基环烷基吡咯烷（哌啶）螺内酰胺和酰胺的制备方法，以及其中间体。
• Synthesis and application in asymmetric C–C bond formation of solution phase ligand libraries of monodentate phosphoramidites
  作者：Ate Duursma、Laurent Lefort、Jeroen A. F. Boogers、André H. M. de Vries、Johannes G. de Vries、Adriaan J. Minnaard、Ben L. Feringa

  DOI：10.1039/b404996a

  日期：——

  A library of 96 unique monodentate phosphoramidite ligands has been synthesized in solution and used in the asymmetric conjugate addition of potassium vinyltrifluoroborate to enones resulting in up to 88% ee.

  合成了96种独特的单齿膦酰胺配体库，并在不对称共轭加成反应中应用于乙酸乙烯基三氟硼酸钾与烯酮的反应，产物的对映体过量率最高可达88%。
• Synthesis, characterization, and catalytic application of a new chiral P,N-indene ligand derived from (R)-BINOL
  作者：Dominik Wechsler、Gabriele Schatte、Mark Stradiotto

  DOI：10.1016/j.jorganchem.2009.02.015

  日期：2009.5

  with triethylamine afforded the crystallographically characterized enantiopure P,N-indene 3 in 71% isolated yield. In the course of rhodium coordination chemistry studies involving 3, the formation of the isolable complex [(κ2-P,N-3)(κ1-P,N-3)RhCl] (7) (81%) was observed, thereby confirming the propensity of this new ligand to form LnRh(3)2 complexes. Such coordination chemistry behavior may contribute

  将2-二甲基氨基茚基锂化，然后用[（R）-（1,1'-联萘-2,2'-二基）]氯亚磷酸酯淬灭，并用三乙胺处理，得到晶体学特征为对映体纯的对映体P，N-茚3，分离出71％屈服。在涉及铑配位化学研究过程3，形成的可分离配合物[（κ 2 - P，ñ - 3）（κ 1 - P，N- 3）的RhCl]（7）（81％）中观察到，从而证实了这种新配体形成L n Rh（3）2的倾向复合体。在本文所述的不对称氢化和氢化硅烷化研究中，这种配位化学行为可能部分导致由3和铑前体配合物的混合物表现出的通常较差的催化性能。
• Amino Acid Based Phosphoramidite Ligands for the Rhodium-Catalyzed Asymmetric Hydrogenation
  作者：Pierre-Alain R. Breuil、Joost N. H. Reek

  DOI：10.1002/ejoc.200901044

  日期：2009.12

  were obtained; up to 97 % ee is obtained for the asymmetric hydrogenation of 4 with Sb-1e. For ligands with two sources of chirality match/mismatch effects are observed, the diastereoisomer Sb-1b giving higher selectivity than the diastereoisomer Rb-1b for most of the substrates. The set of phosphoramidite ligands having the flexible and cheap biphenol backbone is developed to study the ability of the

  合成了两组具有 BINOL 主链（Sb-1a-e 和 Rb-1a）或柔性双酚主链（2a-c 和 2f）的基于氨基酸的亚磷酰胺配体，并在不同功能化烯烃的铑催化氢化中进行了评估：衣康酸二甲酯(3)、2-乙酰氨基丙烯酸甲酯(4)、α-乙酰氨基肉桂酸甲酯(5)和N-(3,4-二氢-2-萘基)乙酰胺(6)。氨基酸片段可以在三个位置 (R1–R3) 进行修饰，从而产生模块化配体。改变氨基酸片段 R1 位置的初始实验表明，缬氨酸基亚磷酰胺配体 Sb-1b 对当前研究的四种底物中的三种形成最具选择性的铑催化剂。其他位置（R2 和 R3）的修饰调整了配体结构，从而提高了选择性；4 与 Sb-1e 的不对称氢化获得高达 97% 的 ee。对于具有两个手性匹配/错配效应来源的配体，对于大多数底物，非对映异构体 Sb-1b 比非对映异构体 Rb-1b 具有更高的选择性。开发了一组具有灵活且廉价的双酚主链的亚磷酰胺
• PHOSPHORAMIDITE LIGAND AND PRODUCTION METHOD OF ALLYLIC AMINE USING THE SAME
  申请人：CARREIRA Erick M.

  公开号：US20090054689A1

  公开（公告）日：2009-02-26

  The present invention provides a production method of an allylic amine represented by the formula (III): wherein R 3 is as defined in the specification, which comprises reacting by an allylic alcohol represented by the formula (II): wherein R 3 is as defined in the specification, with sulfamic acid, in the presence of a phosphoramidite ligand represented by the formula (I): wherein each symbol is as defined in the specification, and an iridium complex. According to the present invention, a primary allylic amine can be produced directly from an allylic alcohol, without use of an activator for an allylic alcohol and conversion of an allylic alcohol into an activated compound thereof.

  本发明提供了一种制备烯丙胺的生产方法，烯丙胺的化学式为(III)，其中R3如规范中定义，该方法包括使用磷酰胺配体(I)和铱配合物，在磺酸的存在下，将烯丙醇(II)与磺酸反应。根据本发明，可以直接从烯丙醇中生产出主要的烯丙胺，而无需使用烯丙醇的活化剂，也无需将烯丙醇转化为其活化化合物。