1-(4-[2-pyrrolidinoethoxy]phenyl)-2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalene

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(4-[2-pyrrolidinoethoxy]phenyl)-2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalene
• 英文别名: (1RS,2SR)-1-(4-[2-pyrrolidinoethoxy]phenyl)-2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalene；cis-1-{2-[4-(2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-phenoxy]ethyl}pyrrolidine；1-[2-[4-[(1S,2R)-6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl]phenoxy]ethyl]pyrrolidine
• 化学式: C₂₉H₃₃NO₂
• 分子量: 427.587
• InChiKey: NAPIZYZVKMASNP-LMSSTIIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-[2-pyrrolidinoethoxy]phenyl)-2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalene 在 三溴化硼 作用下， 生成 拉索昔芬
  参考文献：
  名称：

  新型强效非甾体雌激素受体激动剂/拮抗剂CP-336156（一种二芳基四氢萘）的发现和临床前药理作用。

  摘要：

  DOI：

  10.1021/jm980048b
• 作为产物：
  描述：

  N-(2-氯乙基)吡咯烷 在 palladium dihydroxide 氢气 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-[2-pyrrolidinoethoxy]phenyl)-2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  通过新型三组分偶联反应快速合成拉索昔芬和萘夫昔定

  摘要：

  在 HfCl 4 存在下，通过 4-新戊酰氧基苯甲醛 (5)、肉桂基三甲基硅烷 (6) 和苯甲醚之间的新型三组分偶联反应，简单有效地合成 lasofoxifene (4)，一种可能的缓解骨质疏松症的候选药物是插图。进行偶联产物的连续阳离子环化、烯烃形成和双键迁移，以通过非常简洁的程序提供拉索昔芬 (4) 和萘福昔定 (3) 的常见合成中间体。

  DOI：

  10.1246/cl.2007.40

文献信息

• An<i>ortho</i>-Quinodimethane Route to Lasofoxifene and U23469
  作者：Hiroto Yoshida、Ryuma Yoshida、Masashi Mukae、Joji Ohshita、Ken Takaki

  DOI：10.1246/cl.2011.1272

  日期：2011.11.5

  Lasofoxifene, a third-generation selective estrogen receptor modulator, could be synthesized via regio- and stereoselective [4 + 2] cycloaddition between an ortho-quinodimethane and a borylalkene. This protocol was also applicable to the synthesis of antiestrogen U23469.

  拉索昔芬是一种第三代选择性雌激素受体调节剂，可通过原位二甲烷和硼烷烃之间的[4 + 2]环加成反应进行区域和立体选择性合成。该方法也适用于合成抗雌激素 U23469。
• METHOD FOR THE PREPARATION OF LASOFOXIFENE
  申请人：Lustig Petr

  公开号：US20100256394A1

  公开（公告）日：2010-10-07

  A method of preparing (−)-cis-(5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol D-tartrate-lasofoxifene of formula 1, comprising the following steps a) Preparation of cis-1-2-[4-(2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-phenoxy]ethyl}pyrrolidine of formula (3) by alkylation of cis-1-(4-hydroxyphenyl)-2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalene with 1-(2-chloroethyl)pyrrolidine base or its salt, b) Deprotection of the hydroxyl group in the substance of formula (3) by the effect of hydrobromic acid generating cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol hydrobromide of formula (2a), c) Conversion of the substance of formula (2a) into cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol of formula (2b), d) Preparation of lasofoxifene of formula (1) by conversion into the corresponding diasteroisomer by reaction with D-tartaric acid and crystallization.

  制备(−)-顺式-(5R,6S)-6-苯基-5-[4-(2-吡咯烷-1-基乙氧)苯基]-5,6,7,8-四氢萘-2-醇D-酒石酸盐-拉索福辛的方法，包括以下步骤：a）通过将顺式-1-2-[4-(2-苯基-6-甲氧基-1,2,3,4-四氢萘-1-基)-苯氧基]乙基}吡咯烷的式（3）与1-(2-氯乙基)吡咯烷碱或其盐烷基化，制备式（3）的化合物；b）通过氢溴酸作用去保护式（3）中的羟基，生成式（2a）的顺式-6-苯基-5-[4-(2-吡咯烷-1-基乙氧)苯基]-5,6,7,8-四氢萘-2-醇氢溴酸盐；c）将式（2a）的化合物转化为式（2b）的顺式-6-苯基-5-[4-(2-吡咯烷-1-基乙氧)苯基]-5,6,7,8-四氢萘-2-醇；d）通过与D-酒石酸反应并结晶，将化合物转化为相应的对映异构体，制备式（1）的拉索福辛。
• Synthesis of Lasofoxifene, Nafoxidine and Their Positional Isomers via the Novel Three-Component Coupling Reaction
  作者：Kenya Nakata、Yoshiyuki Sano、Isamu Shiina

  DOI：10.3390/molecules15106773

  日期：——

  A Lewis acid-mediated three-component coupling reaction was successfully applied for the synthesis of lasofoxifene (1), nafoxidine (2), and their positional isomers, inv-lasofoxifene (3) and inv-nafoxidine (4). In the presence of HfCl4, the desired one-pot coupling reaction among 4-pivaloyloxybenzaldehyde (5), cinnamyltrimethylsilane (6), and anisole proceeded to afford the corresponding 3,4,4-triaryl-1-butene 7 in high yield. The iodocarbocyclization of the coupling product and the successive elimination of hydrogen iodide forming the olefin part, followed by the migration of the double-bond afforded the common synthetic intermediate of lasofoxifene (1) and nafoxidine (2) via a very concise procedure. Additionally, the syntheses of their positional isomers inv-lasofoxifene (3) and inv-nafoxidine (4) were also achieved through very convenient protocols.

  路易斯酸介导的三组分偶联反应被成功地用于合成拉索昔芬（1）、萘福昔定（2）以及它们的位置异构体 inv-lasofoxifene (3) 和 inv-nafoxidine (4)。在 HfCl4 存在下，4-pivaloyloxy 苯甲醛 (5)、肉桂基三甲基硅烷 (6) 和苯甲醚发生了所需的一锅偶联反应，以高产率得到了相应的 3,4,4-三芳基-1-丁烯 7。耦合产物的碘代碳环化和形成烯烃部分的碘化氢的连续消除，以及随后的双键迁移，通过非常简洁的程序得到了拉索昔芬（1）和萘福昔定（2）的常见合成中间体。此外，它们的位置异构体 inv-lasofoxifene (3) 和 inv-nafoxidine (4) 也是通过非常简便的方法合成的。
• STEREOSELECTIVE HYDROGENATION PROCESS FOR PREPARING CIS-6-PHENYL-5-[4-(2-PYRROLIDIN-1-YL-ETHOXY)-PHENYL]-2-METHOXY-5,6,7,8-TETRAHYDRONAPHTHALENE HYDROCHLORIDE
  申请人：Taber Geraldine Patricia

  公开号：US20100160648A1

  公开（公告）日：2010-06-24

  This invention provides an improved process for preparing cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2-methoxy-5,6,7,8-tetrahydronaphthalene hydrochloride which is an intermediate for the preparation of (−)-cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol which is useful for the treatment of osteoporosis.

  该发明提供了一种改进的制备cis-6-苯基-5-[4-(2-吡咯烷-1-基-乙氧基)-苯基]-2-甲氧基-5,6,7,8-四氢萘盐酸盐的过程，该盐酸盐是制备(−)-cis-6-苯基-5-[4-(2-吡咯烷-1-基-乙氧基)-苯基]-5,6,7,8-四氢萘酚的中间体，该酚对治疗骨质疏松症有用。
• Nickel-Catalyzed Stereoselective Diarylation of Alkenylarenes
  作者：Pin Gao、Liang-An Chen、M. Kevin Brown

  DOI：10.1021/jacs.8b05680

  日期：2018.8.29

  A three-component coupling of aryl bromides, arylboron reagents, and alkenylarenes is presented. The method tolerates a variety of substitution patterns on all of the components. In particular, 1,2-disubstituted alkenylarenes are suitable and undergo highly diastereoselective diarylation.