1-(3-羟基金刚烷-1-基)乙酮 | 39917-38-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(3-羟基金刚烷-1-基)乙酮
• 中文别名: 3-羟基-1-乙酰金刚烷；1-(3-羟基-1-金刚烷)-乙酮
• 英文名称: 3-hydroxy-1-adamantyl methyl ketone
• 英文别名: 1-acetyl-3-hydroxyadamantane；1-(3-hydroxyadamantan-1-yl)ethanone；3-hydroxy-1-acetyladamantane；3-hydroxy-1-adamantane methyl ketone；1-hydroxy-3-acetyladamantane；1-(3-Hydroxy-1-adamantyl)ethanone
• CAS: 39917-38-9
• 化学式: C₁₂H₁₈O₂
• mdl: MFCD03147416
• 分子量: 194.274
• InChiKey: ISGGLYJERYAKTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.916
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2914400090

反应信息

• 作为反应物：
  描述：

  1-(3-羟基金刚烷-1-基)乙酮 在 三氯化铝 、 硫酸 作用下， 反应 17.0h， 生成 1-acetyl-3-phenyladamantane
  参考文献：
  名称：

  摘要：

  DOI：

  10.1023/a:1026090119628
• 作为产物：
  描述：

  1-金刚烷甲酮 在 二甲基二环氧乙烷 作用下， 以 丙酮 为溶剂， 反应 24.0h， 生成 1-(3-羟基金刚烷-1-基)乙酮
  参考文献：
  名称：

  Linear Free Energy Relationship Studies of the Dimethyldioxirane C-H Bond Insertion Reaction

  摘要：

  The relative rates of reaction of a series of p-substituted cumenes with dimethyldioxrane have been studied. The products are the corresponding cumyl alcohols. Treatment of the rate data with the Hammett substituent constants reveals that the insertion reaction is an electrophilic process with rho = -2.76. Similar treatment of the data with the Brown-Okamoto substituent constants gives rho(+) = -1.61. The second-order rate constants for the reaction of a series of substituted adamantanes with dimethyldioxirane were also determined. Again, the products are the corresponding adamantanols. The rate constants were correlated with several types of substituent constants. The best correlations were obtained with the Taft sigma(*) and sigma(I) constants which gave rho(*) = -1.08 and rho(I) -2.39, respectively. Thus, the insertion reaction in this aliphatic system is also electrophilic.

  DOI：

  10.1021/jo00122a059

文献信息

• [EN] FUSED-RING COMPOUNDS, PHARMACEUTICAL COMPOSITION AND USES THEREOF<br/>[FR] COMPOSÉS À CYCLES CONDENSÉS, COMPOSITION PHARMACEUTIQUE ET UTILISATIONS ASSOCIÉES
  申请人：SHANGHAI DE NOVO PHARMATECH CO LTD

  公开号：WO2016131380A1

  公开（公告）日：2016-08-25

  This disclosure is related to a fused-ring compound of formula (I) and/or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the fused ring compound of formula (I) and/or a pharmaceutically acceptable salt thereof, preparation methods thereof, and use thereof in modulating activity of indoleamine 2, 3-dioxygenase (IDO) and/or tryptophan 2, 3-dioxygenase (TDO). This disclosure further provides methods of treating IDO and/or TDO-associated diseases, including cancer, viral infection and autoimmune diseases.

  这份披露涉及到式(I)的融合环化合物和/或其药学上可接受的盐，包括式(I)的融合环化合物和/或其药学上可接受的盐的药物组合物，其制备方法，以及在调节吲哚胺2,3-二氧化酶(IDO)和/或色氨酸2,3-二氧化酶(TDO)活性中的应用。这份披露还提供了治疗IDO和/或TDO相关疾病的方法，包括癌症、病毒感染和自身免疫疾病。
• Adamantanemethanol derivatives and production processes thereof
  申请人：Daicel Chemical Industries, Ltd.

  公开号：US06344590B1

  公开（公告）日：2002-02-05

  An adamantanemethanol derivative of the invention is represented by the following formula (1), wherein Ra is a hydrogen atom or a hydrocarbon group; Rb is a hydrocarbon group having a carbon atom, to which carbon atom at least one hydrogen atom is bonded, at a bonding site with the adjacent carbon atom; Rc, Rd and Re are each a hydrogen atom, a hydroxyl group which may be protected by a protective group or the like; provided that a hydroxyl group protected by a protective group or the like is bonded to at least one carbon atom constituting the adamantane skeleton when Ra is a hydrogen atom or a methyl group and Rb is a methyl group; and at least one substituent, in addition to the HO—C(Ra)(Rb)— group indicated in the formula (1), is bonded to the adamantane ring when one of Ra and Rb is a methyl group and the other is an ethyl group.

  该发明的一种金刚烷甲醇衍生物由以下式（1）表示，其中Ra是氢原子或烃基；Rb是具有碳原子的烃基，该碳原子上至少有一个氢原子与相邻碳原子结合在一起；Rc、Rd和Re分别是氢原子、可能被保护基团保护的羟基或类似物；前提是当Ra是氢原子或甲基且Rb是甲基时，至少一个被保护基团保护的羟基与构成金刚烷骨架的至少一个碳原子结合在一起；当Ra和Rb中的一个是甲基而另一个是乙基时，除了式（1）中指示的HO—C（Ra）（Rb）—基团之外，至少有一个取代基与金刚烷环结合。
• An Efficient and Practical Method for the Synthesis of Saxagliptin Intermediate 2-(3-Hydroxy-1-adamantane)-2-oxoacetic Acid and Its Optimization
  作者：Qi Liao、Lan Jiang、Cong Li、Yaling Shen、Min Wang、Chengkun Cao、Xiangnan Hu

  DOI：10.1155/2019/5375670

  日期：2019.10.10

  A mild and relatively simple way for preparation of 2-(3-hydroxy-1-adamantane)-2-oxoacetic acid (I) was reported. It was prepared from 1-adamantanecarboxylic acid (II) via sulfuric acid/nitric acid to get 3-hydroxy-1-adamantanecarboxylic acid (III); treated with the one-pot method through acylation, condensation, and decarboxylation to obtain 3-hydroxy-1-acetyladamantane (IV); and finally oxidized

  报道了一种温和且相对简单的制备 2-(3-羟基-1-金刚烷)-2-氧代乙酸 (I) 的方法。由1-金刚烷甲酸(II)经硫酸/硝酸制得3-羟基-1-金刚烷甲酸(III)；用一锅法酰化、缩合、脱羧得到3-羟基-1-乙酰金刚烷(IV)；最后用高锰酸钾（KMnO4）氧化得到目标化合物（I）。总收率约为60%，为沙格列汀中间体的商业化生产提供了新思路。
• An Improved Synthetic Method of Saxagliptin Intermediate 3-Hydroxy-1- acetyladamantane and Its Characterization
  作者：Run Gan、Jing Zhou、Jie Li、Ming Zhang、Xue Jiang、Xiangnan Hu

  DOI：10.2174/1570178613666160830160805

  日期：2016.10.25

  method started from 1-adamantanecarboxylic acid via oxidation by sulfuric acid/nitric acid, then VHA reagent (SOCl2/DMF) and sodium diethyl malonate were used in one-pot through acylation, substitution, decarboxylation and alkalization to give the target compound. It is an improved method that VHA reagent (SOCl2/DMF) was used in the step of acylation which effectively enhanced the total yield up to 74%

  报道了一种改进的具有高产率和简单步骤的3-羟基-1-乙酰金刚烷的合成方法。3-羟基-1-乙酰金刚烷是沙格列汀用于2型糖尿病（T2DM）的重要中间体。它的合成方法从1-金刚烷羧酸经硫酸/硝酸氧化开始，然后通过酰化，取代，脱羧和碱化反应一锅使用VHA试剂（SOCl2 / DMF）和丙二酸二乙酯钠，得到目标化合物。这种改进的方法是在酰化步骤中使用VHA试剂（SOCl2 / DMF），有效地将总收率提高了74％，并且通过一锅法有效地简化了操作。合成的目标化合物已经通过单晶X射线衍射表征。
• A facile and economic method for the synthesis of (S)-N-Boc-3′-hydroxyadamantylglycine
  作者：Jie Li、Xue Jiang、Run Gan、Ming Zhang、Xinmei Pan、Xiangnan Hu

  DOI：10.1007/s11164-015-2398-2

  日期：2016.6

  ic acid (4), then through oximation, reduction and (Boc)2O protection to give the N -Boc-3′-hydroxyadamantylglycine(6), then was treated with quinidine to get (S)- N -Boc-3′-hydroxyadamantylglycine(I) and quinine to get (R)– N -Boc-3′-hydroxyadamantylglycine(II). Finally, Compound II was racemized by dicyclohexylcarbodiimide (DCC) and sodium hydride (NaH) to afford compound 6. In this route, the overall

  （S） -N -Boc-3'-羟基金刚烷基甘氨酸 （I）是沙格列汀用于2型糖尿病（T2DM）的重要中间体。由1-金刚烷羧酸（1）与硫酸/硝酸，VHA试剂（SOCl 2 / DMF）和丙二酸二乙酯钠温和反应制得，然后进行水解，脱羧，碱化和氧化处理，得到2-（ 3-羟基-1-金刚烷基）-2-氧乙酸（4），然后通过肟化，还原和（Boc）2 O保护得到 N - Boc -3'-羟基金刚烷基甘氨酸 （6），然后用奎尼丁处理得到（S） -N -Boc-3′-羟基金刚烷基甘氨酸 （I）和奎宁得到（R）– N -Boc-3'-羟基金刚烷基甘氨酸（II）。最后，用二环己基碳二亚胺（DCC）和氢化钠（NaH）使化合物II消旋，得到化合物6。在这种方法中，制备化合物I的总产率为约35％，对映体过量（ee）达到99％。该途径为制备（S） -N -Boc-3'-羟基金刚烷基甘氨酸 提供了新思路 。