(1,1-diethoxy-ethyl)(difluoromethyl)-phosphinic acid ethyl ester | 139474-89-8

• 分子结构分类: 有机化合物 - 有机磷化合物 - 有机膦酸及其衍生物
• 英文名称: (1,1-diethoxy-ethyl)(difluoromethyl)-phosphinic acid ethyl ester
• 英文别名: difluoromethyl-(1,1-diethoxy-ethyl)-phosphinic acid ethyl ester；ethyl (difluoromethyl)(1,1-diethoxyethyl)phosphinate；ethyl, 1,1-diethoxyethyl(difluoromethyl)phosphinate；ethyl 1,1-diethoxyethyl(difluoromethyl)phosphinate；1-[difluoromethyl(ethoxy)phosphoryl]-1,1-diethoxyethane
• CAS: 139474-89-8
• 化学式: C₉H₁₉F₂O₄P
• 分子量: 260.218
• InChiKey: FKDGWAGBRMBRHB-UHFFFAOYSA-N

物化性质

• 沸点：
  245.6±50.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1,1-diethoxy-ethyl)(difluoromethyl)-phosphinic acid ethyl ester 在 三甲基氯硅烷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 48.0h， 以100%的产率得到ethyl (difluoromethyl)phosphinate
  参考文献：
  名称：

  GABA的膦酸类似物。1.新的强效和选择性GABAB激动剂。

  摘要：

  抗痉挛剂和肌肉松弛剂巴氯芬1是对双小分子不敏感的GABA B受体的有效选择性激动剂。多年来，获得出色的GABA B激动剂的努力一直没有成功。我们描述了两个新系列的GABA B激动剂的合成和生物学特性，在体外和体内，最好的化合物比巴氯芬更有效。它们是通过用次膦酸或甲基次膦酸残基取代GABA或巴氯芬衍生物的羧酸基团而获得的。出人意料的是，GABA的乙基和高级烷基次膦酸衍生物产生了新型GABAB拮抗剂，在本系列的第2部分中对此进行了描述。

  DOI：

  10.1021/jm00017a015
• 作为产物：
  描述：

  ethyl (1,1-diethoxyethyl)phosphinate 以 四氢呋喃 、 氟里昂-22 、 水 为溶剂， 生成 (1,1-diethoxy-ethyl)(difluoromethyl)-phosphinic acid ethyl ester
  参考文献：
  名称：

  Substituted propane-phosphinic acid compounds

  摘要：

  式I的化合物##STR1##其中R表示具有2个或更多碳原子的脂肪族、环脂族、环脂族-脂肪族或芳基脂肪族基团，其中R.sup.1、R.sup.2和R.sup.3中的一个代表氢或脂肪族、环脂族、芳基脂肪族或芳香族基团，R.sup.1、R.sup.2和R.sup.3中的另一个是氢或在R.sup.1和R.sup.2的情况下是羟基，而R.sup.1、R.sup.2和R.sup.3中的剩余一个是氢，或者R表示甲基，R.sub.1表示氢或羟基，R.sub.2表示芳香族基团，R.sub.3表示氢，它们的盐具有GABA.sub.B-拮抗性质，可用作GABA.sub.B-拮抗剂。当在式II的化合物中获得时##STR2##其中R、R.sup.1、R.sup.2和R.sup.3具有其先前的含义，Z表示--NH.sub.2，R.sup.4表示羟基保护基R.sup.5或者当R.sup.1和R.sup.3表示氢且R.sup.2表示氢或烷基时，表示碱金属或铵离子R.sup.6，或者Z表示受保护或潜在的氨基团Z.degree.，而R.sup.4表示氢或羟基保护基R.sup.5，任何一个R.sup.5或R.sup.6基团被氢取代，和/或任何一个Z.degree.基团被转化为--NH.sub.2。

  公开号：

  US05051524A1

文献信息

• Phosphinic Acid Analogs of GABA. 2. Selective, Orally Active GABAB Antagonists
  作者：Wolfgang Froestl、Stuart J. Mickel、Georg von Sprecher、Peter J. Diel、Roger G. Hall、Ludwig Maier、Dietrich Strub、Vito Melillo、Peter A. Baumann

  DOI：10.1021/jm00017a016

  日期：1995.8

  In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al.(5) described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in, vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in Various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.
• Alkylation of <i>H</i>-Phosphinate Esters under Basic Conditions
  作者：Isabelle Abrunhosa-Thomas、Claire E. Sellers、Jean-Luc Montchamp

  DOI：10.1021/jo062436o

  日期：2007.4.1

  An efficient and general procedure was developed for the direct alkylation of H-phosphinate esters with LHMDS at low temperature. The simplicity of the reaction allows the use of various H-phosphinate esters and takes place with a wide range of electrophiles. The approach can be employed to access some GABA analogues or precursors to GABA analogues. The isolated yields are moderate to good. This is the first report of an alkylation with a secondary iodide or a primary chloride.
• Synthesis and reactivity studies of α,α-difluoromethylphosphinates
  作者：Isabelle Abrunhosa-Thomas、Laëtitia Coudray、Jean-Luc Montchamp

  DOI：10.1016/j.tet.2010.04.036

  日期：2010.6

  The preparation and reactivity of some a,alpha-difluorophosphinates are investigated. Alkylation of H-phosphinates with LiHMDS and ClCF2H gives the corresponding alpha,alpha-difluorophosphinates in good yield. Deprotonation of these reagents with alkyllithium or LDA is then studied. Subtle electronic effects translate into significant differences in the deprotonation/alkylation of the two 'Ciba-Geigy reagents' (EtO)(2)CRP(O)(OEt)H (R=H, Me). On the other hand, attempted methylation of difluoromethyl-octyl-phosphinic acid butyl ester resulted in the exclusive alkylation of the octyl chain. Finally, reaction with carbonyl compounds results in the formation of 1,1 -difluoro-2-phosphinoyl compounds. (C) 2010 Elsevier Ltd. All rights reserved.
• US5013863A
  申请人：——

  公开号：US5013863A

  公开（公告）日：1991-05-07
• US5051524A
  申请人：——

  公开号：US5051524A

  公开（公告）日：1991-09-24