4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid | 118528-87-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid
• CAS: 118528-87-3
• 化学式: C₁₀H₁₀Cl₂O₃
• 分子量: 249.094
• InChiKey: TXURVWVBXWPFRO-UHFFFAOYSA-N

物化性质

• 沸点：
  422.1±45.0 °C(Predicted)
• 密度：
  1.447±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid 在 咪唑 、 lithium aluminium tetrahydride 、 jones reagent 、 水 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 72.08h， 生成 4-(3,4-dichlorophenyl)-4-phenyl butanoic acid
  参考文献：
  名称：

  SN2铜酸盐置换活化手性苄醇合成4（S）-（3,4-二氯苯基）-3,4-二氢-1（2H）-萘酮

  摘要：

  报道了制备4（S）-（3,4-二氯苯基）-3,4-二氢-1（2H）-萘酮的两种途径。最有效的途径是通过催化不对称的恶唑硼烷催化的γ-酮酸酯还原反应生成手性苄醇，然后将其活化并以SN2方式用较高级的铜酸盐置换。所得叔丁酯的分子内Friedel-Crafts环化得到标题化合物。

  DOI：

  10.1016/s0040-4020(01)88330-7
• 作为产物：
  描述：

  4-(3,4-二氯苯基)-4-氧代丁酸 在 sodium hydroxide 、 sodium tetrahydroborate 作用下， 反应 18.0h， 生成 4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid
  参考文献：
  名称：

  SN2铜酸盐置换活化手性苄醇合成4（S）-（3,4-二氯苯基）-3,4-二氢-1（2H）-萘酮

  摘要：

  报道了制备4（S）-（3,4-二氯苯基）-3,4-二氢-1（2H）-萘酮的两种途径。最有效的途径是通过催化不对称的恶唑硼烷催化的γ-酮酸酯还原反应生成手性苄醇，然后将其活化并以SN2方式用较高级的铜酸盐置换。所得叔丁酯的分子内Friedel-Crafts环化得到标题化合物。

  DOI：

  10.1016/s0040-4020(01)88330-7

文献信息

• Derivatives of 4-hydroxybutanoic acid and of its higher homologue as ligands of $g(g)-hydroxybutyrate (ghb) receptors, pharmaceutical compositions containing same and pharmaceutical uses
  申请人：Bourguignon Jean-Jacques

  公开号：US20050113366A1

  公开（公告）日：2005-05-26

  The invention concerns the field of synthesis organic chemistry applied to the pharmaceutical field and concerns novel derivatives of 4-hydroxybutanoic acid and its higher homologue, 5-hydroxypentanoic acid, their crotonic homologues, pharmaceutical compositions containing them and their pharmaceutical uses. Said novel derivatives are capable of binding with γ-hydroxybutyrate (GHB)-specific receptors and hence capable of exhibiting agonist or antagonist properties, in particular for treating sleep disorders, anxiety and general diseases of the central nervous system. The invention also concerns compounds of general formula (I) wherein the substituents are as defined in the description.

  该发明涉及合成有机化学领域应用于制药领域，涉及4-羟基丁酸及其较高同系物5-羟基戊酸的新颖衍生物，它们的丁烯酸同系物，含有它们的药物组合物以及它们的药用。所述新颖衍生物能够与γ-羟基丁酸盐（GHB）特异性受体结合，因此能够表现出激动剂或拮抗剂特性，特别用于治疗睡眠障碍、焦虑和中枢神经系统的一般疾病。该发明还涉及一般式（I）的化合物，其中取代基如描述中所定义。
• [EN] PROCESS FOR PREPARING KETONE ENANTIOMER
  申请人：PFIZER INC.

  公开号：WO1993012062A1

  公开（公告）日：1993-06-24

  (EN) A novel multi-step process for preparing the (4S^_-enantiomer of 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone in a highly-optically pure form is disclosed. The process involves (1) first esterifying 4-(3,4-dichlorophenyl)-4-ketobutanoic acid with isopropylene or isobutylene to form the corresponding isopropyl or t^_e^_r^_t^_.-butyl 4-(3,4-dichlorophenyl)-4-ketobutanoate; (2) then reducing the ketobutanoic acid ester obtained in the first step with an asymmetric carbonyl reducing agent to form the corresponding chiral isopropyl or t^_e^_r^_t^_.-butyl 4-(3,4-dichlorophenyl)-(4R^_)-hydroxybutanoate; (3) then sulfonylating the (4R^_)-hydroxybutanoic acid ester with methanesulfonyl, benzenesulfonyl or p^_-toluenesulfonyl chloride or bromide in the presence of a standard base to yield the corresponding isopropyl or t^_e^_r^_t^_.-butyl 4-(3,4-dichlorophenyl)-(4R^_)-sulfonyloxybutanoate; (4) next subjecting the 4-sulfonyloxybutanoic acid ester obtained in the third step to a copper-coupling reaction with dilithium diphenyl(cyano)cuprate of the formula $g(F)2Cu(CN)Li2 to effect a stereochemical displacement of the organic (4R^_)-sulfonyloxy group of the (4R^_)-sulfonyloxybutanoic acid ester by the phenyl group of the dilithium diphenylcuprate reagent and so selectively form the corresponding isopropyl or t^_e^_r^_t^_.-butyl 4-(3,4-dichlorophenyl)-(4R^_)-phenylbutanoate, and (5) thereafter cyclizing the stereospecific (4R^_)-phenylated n-butanoic acid ester in the presence of a protic or Lewis acid catalyst to finally yield the desired (4S^_)-4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone compound in a highly-optically pure form. The latter compound, which is a novel (4S^_)-enantiomer per se, has utility as an intermediate that ultimately leads to pure c^_i^_s^_-(1S^_)(4S^_)N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine (sertraline), which is a known antidepressant agent. The aforementioned isopropyl and t^_e^_r^_t^_.-butyl esters of 4-(3,4-dichlorophenyl)-(4R^_)-hydroxybutanoic acid, as well as their corresponding (4R^_)-methanesulfonyl, (4R^_)-benzenesulfonyl and (4R^_)-p^_-toluenesulfonyl derivatives, are also novel compounds, as are the aforementioned isopropyl and t^_e^_r^_t^_.-butyl esters of 4-(3,4-dichlorophenyl)-(4R^_)-phenylbutanoic acid as well as the aforesaid acid per se. These novel chiral compounds are all useful as key intermediates in the overall process of the present invention.(FR) Nouveau procédé de préparation en plusieurs étapes de l'énantiomère-(4S^_)- de 4-(3,4-dichlorophényle)-3,4-dihydro-1(2H)-naphtlanénone, sous forme extrêmement pure du point de vue optique. Dans ce procédé, (1) on estérifie tout d'abord du 4-(3,4-diclorophényle)-4-acide cétobutanoïque avec de l'isopropylène ou de l'isobutylème pour former l'isopropyle ou t^_e^_r^_t^_.-butyle 4-(3,4-dichlorophényle)-4-cétobutanoate correspondant; (2) on réduit ensuite l'ester d'acide cétobutanoïque obtenue dans l'étape (1) avec un agen de réduction au carbonyle asymétrique pour former l'isopropyle chiral ou le t^_e^_r^_t^_.-butyle 4-(3,4-dichlorophényle)(4R^_)-hydroxybutanoate correspondant; (3) on sulfonylate l'ester d'acide (4R^_)-hydroxybutanoïque avec du méthanesulfonyle, du benzènesulfonyle ou du chlorure ou du bromure de p^_-toluènesulfonyle en présence d'une base standard pour produire l'isopropyle ou le t^_e^_r^_t^_.-butyle 4-(3,4-dichlorophényle)-(4R^_)-sulfonyloxybutanoate correspondant; (4) on soumet l'ester d'acide 4-sulfonyl-oxybutanoïque obtenu dans l'étape (3) à une réaction de couplage par le cuivre avec du dilithium diphényle (cyano) cuprate de formule $g(F)2Cu(CN)Li2 pour effectuer un déplacement stéréochimique du groupe organique (4R^_)-sulfonyloxy de l'ester d'acide (4R^_)-sulfonyloxybutanoïque par le groupe phényle du réactif au dilithium diphénylcuprate et pour former ainsi de manière sélective l'isopropyle ou le t^_e^_r^_t^_.-butyle 4-(3,4-dichlorophényle)-(4R^_)-phénylbutanoate correspondant; et (5) on cyclise l'ester d'acide n-butanoïque (4R^_)-phényle stéréospécifique en présence d'un catalyseur d'acide protique ou d'acide Lewis pour produire finalement le composé désiré de (4S^_)-4-(3,4-dichlorophényle)-3,4-dihydro-1(2H)-naphthalénone sous forme extrêmement pure du point de vue optique. Ce composé qui est un nouvel énantiomère-(4S^_) en soi est utile comme intermédiaire qui conduit à produire de la c^_i^_s^_-(1S^_)(4S^_)-N-méthyle-4-(3,4-dichlorophényle)-1,2,3,4-tétrahydro-1-naphthalèneamine (sertraline) pure qui est un agent antidépresseur connu. Les procédents esters d'isopropyle et de t^_e^_r^_t^_.-butyle de 4-(3,4-dichlorophényle)-(4R^_)- acide hydroxybutanoïque ainsi que leurs dérivés correspondants (4R^_)-p^_-toluènesulfonyle sont également de noveaux composés, tout comme les esters d'isopropyle et de t^_e^_r^_t^_.-butyle précédemment décrits de 4-(3,4-dichlorophényle)-(4R^_)- acide phénylbutanoïque ainsi que l'acide précité en lui-même. Tous ces nouveaux composés chiraux sont utiles comme intermédiaires dans le procédé global de cette invention.

  本发明揭示了一种新的多步骤制备高度光学纯度的(4S^_)-4-(3,4-二氯苯基)-3,4-二氢-1(2H)-萘酮的过程。该过程包括(1)首先用异丙烯或异丁烯酯化4-(3,4-二氯苯基)-4-酮丁酸，形成相应的异丙基或叔丁基4-(3,4-二氯苯基)-4-酮丁酸酯；(2)然后用不对称的羰基还原剂还原第一步得到的酮丁酸酯，形成相应的手性异丙基或叔丁基4-(3,4-二氯苯基)-(4R^_)-羟基丁酸酯；(3)然后在标准碱的存在下，用甲磺酰、苯磺酰或p^_-甲苯磺酰氯或溴磺酰化(4R^_)-羟基丁酸酯，得到相应的异丙基或叔丁基4-(3,4-二氯苯基)-(4R^_)-磺酰氧基丁酸酯；(4)接下来将第三步得到的4-磺酰氧基丁酸酯与$g(F)2Cu(CN)Li2的二锂二苯基(氰)铜反应，使有机(4R^_)-磺酰氧基团被二锂二苯基铜试剂的苯基选择性地置换，从而选择性地形成相应的异丙基或叔丁基4-(3,4-二氯苯基)-(4R^_)-苯基丁酸酯；(5)然后在质子性或路易斯酸催化剂的存在下，环化立体选择性的(4R^_)-苯基化正丁酸酯，最终得到所需的高度光学纯度的(4S^_)-4-(3,4-二氯苯基)-3,4-二氢-1(2H)-萘酮化合物。后者是一种新的(4S^_)-对映体，可用作导致纯c^_i^_s^_-(1S^_)(4S^_)N-甲基-4-(3,4-二氯苯基)-1,2,3,4-四氢-1-萘胺(舍曲林)的中间体，后者是一种已知的抗抑郁剂。前述4-(3,4-二氯苯基)-(4R^_)-羟基丁酸酯的异丙基和叔丁基酯，以及它们相应的(4R^_)-甲磺酰、(4R^_)-苯磺酰和(4R^_)-p^_-甲苯磺酰衍生物，也是新的化合物，同样，前述4-(3,4-二氯苯基)-(4R^_)-苯基丁酸酯的异丙基和叔丁基酯以及上述酸本身也是新的化合物。这些新的手性化合物都可用作本发明的整体过程中的关键中间体。
• Process for preparing sertraline intermediates
  申请人：Pfizer, Inc.

  公开号：US04839104A1

  公开（公告）日：1989-06-13

  A novel three-step process for preparing 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid is disclosed, which involves (1) reducing 4-(3,4-dichlorophenyl)-4-ketobutanoic acid to 4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid; (2) then converting the intermediate hydroxy acid formed in the first step to 5-(3,4-dichlorophenyl)-dihydro-2(3H)-furanone, and (3) thereafter reacting the resulting gamma-butyrolactone compound with benzene in a Friedel-Crafts type reaction to form the desired final product. The latter compound is known to be useful as an intermediate leading to 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone and ultimately, to cis-(1S)(4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthal ene amine (sertraline), which is known to be a preferred anti-depressant agent in the field of medicinal chemistry. The aforementioned 5-(3,4-dichlorophenyl)-dihydro-2(3H)-furanone and 4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid are both novel compounds. There is also disclosed a novel process for converting 5-(3,4-dichlorophenyl)-dihydro-2(3H)-furanone directly to 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone, as well as an alternate novel process for converting 4-(3,4-dichlorophenyl)-4-hydroxybutanoic acid directly to this same key intermediate.

  本文介绍了一种制备4-(3,4-二氯苯基)-4-苯基丁酸的新型三步法，包括(1)将4-(3,4-二氯苯基)-4-酮丁酸还原为4-(3,4-二氯苯基)-4-羟基丁酸；(2)然后将第一步中形成的中间体羟基酸转化为5-(3,4-二氯苯基)-二氢-2(3H)-呋喃酮；(3)随后在Friedel-Crafts类型反应中将所得的γ-丁内酯化合物与苯反应，形成所需的最终产物。后者化合物已知可用作导向4-(3,4-二氯苯基)-3,4-二氢-1(2H)-萘酮的中间体，最终导向cis-(1S)(4S)-N-甲基-4-(3,4-二氯苯基)-1,2,3,4-四氢-1-萘胺(舍曲林)，后者已知为医药化学领域中首选的抗抑郁剂。前述的5-(3,4-二氯苯基)-二氢-2(3H)-呋喃酮和4-(3,4-二氯苯基)-4-羟基丁酸均为新型化合物。本文还介绍了一种将5-(3,4-二氯苯基)-二氢-2(3H)-呋喃酮直接转化为4-(3,4-二氯苯基)-3,4-二氢-1(2H)-萘酮的新型方法，以及将4-(3,4-二氯苯基)-4-羟基丁酸直接转化为同一关键中间体的另一种新型方法。
• Friedel-Crafts synthesis of 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone, a key intermediate in the preparation of the antidepressant sertraline
  作者：George J. Quallich、Michael T. Williams、Robert C. Friedmann

  DOI：10.1021/jo00303a046

  日期：1990.8
• Process for preparing a 4,4-diphenylbutanoic acid derivative
  申请人：PFIZER INC.

  公开号：EP0295050B1

  公开（公告）日：1991-04-17