3-[2-(4-Benzyloxy-benzoyl)-5-methoxy-phenyl]-1-phenyl-propan-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-[2-(4-Benzyloxy-benzoyl)-5-methoxy-phenyl]-1-phenyl-propan-1-one
• 英文别名: 3-[5-methoxy-2-(4-phenylmethoxybenzoyl)phenyl]-1-phenylpropan-1-one
• 化学式: C₃₀H₂₆O₄
• 分子量: 450.534
• InChiKey: WQRDHSBFQYMBGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-[2-(2-bromo-5-methoxy-phenyl)-ethyl]-2-phenyl-[1,3]dioxolane 、 正丁基锂 、 4-苯甲氧基苯甲腈 、 4-甲基苯磺酸吡啶 在 氯化铵 作用下， 以 四氢呋喃 、 丙酮 、 水 为溶剂， 反应 34.0h， 以afforded an unoptimized weight of 0.8 g 3-[2-(4-Benzyloxy-benzoyl)-5-methoxy-phenyl]-1-phenyl-propan-1-one的产率得到3-[2-(4-Benzyloxy-benzoyl)-5-methoxy-phenyl]-1-phenyl-propan-1-one
  参考文献：
  名称：

  Process for Cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine

  摘要：

  本发明提供了一种改进的过程，用于制备（-）顺式-6-苯基-5-[4-(2-吡咯烷基乙氧基)苯基]-5,6,7,8-四氢萘酚的中间体cis-1-{2-[4-(6-甲氧基-2-苯基-1,2,3,4-四氢萘基)苯氧]乙基}吡咯烷。该化合物对骨质疏松症的治疗具有用处。

  公开号：

  US06323345B1

文献信息

• 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。
• Process for cis-1{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy] ethyl}pyrrolidine
  申请人：Pfizer Inc.

  公开号：US06395911B1

  公开（公告）日：2002-05-28

  This invention provides an improved process for cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine 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.

  这项发明提供了一种改进的过程，用于制备cis-1-（2-（4-（6-甲氧基-2-苯基-1,2,3,4-四氢萘-1-基）苯氧）乙基）吡咯烷，该化合物是制备（-）cis-6-苯基-5-（4-（2-吡咯烷基乙氧）苯基）-5,6,7,8-四氢萘酚的中间体，该化合物对于治疗骨质疏松症是有用的。
• Intermediates in a process for cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine
  申请人：Pfizer Inc.

  公开号：US06232476B1

  公开（公告）日：2001-05-15

  This invention provides an improved process for cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine 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.

  本发明提供了一种改进的过程，用于制备cis-1-{2-[4-(6-甲氧基-2-苯基-1,2,3,4-四氢萘-1-基)苯氧]乙基}吡咯烷，该化合物是制备用于治疗骨质疏松症的(-)cis-6-苯基-5-[4-(2-吡咯烷基-1-乙氧基)-苯基]-5,6,7,8-四氢萘酚的中间体。
• Process for Cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine
  申请人：Pfizer Inc.

  公开号：US06323345B1

  公开（公告）日：2001-11-27

  This invention provides an improved process for cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine 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.

  本发明提供了一种改进的过程，用于制备（-）顺式-6-苯基-5-[4-(2-吡咯烷基乙氧基)苯基]-5,6,7,8-四氢萘酚的中间体cis-1-{2-[4-(6-甲氧基-2-苯基-1,2,3,4-四氢萘基)苯氧]乙基}吡咯烷。该化合物对骨质疏松症的治疗具有用处。
• Process for cis-1- 2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl pyrrolidine
  申请人：Pfizer Products Inc.

  公开号：EP1055658A2

  公开（公告）日：2000-11-29

  This invention provides an improved process for cis-1-2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine of following formula: 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.

  本发明提供了一种下式的顺式-1-2-[4-(6-甲氧基-2-苯基-1,2,3,4-四氢萘-1-基)苯氧基]乙基}吡咯烷的改进工艺： 是制备(-)顺式-6-苯基-5-[4-(2-吡咯烷-1-基乙氧基)苯基]-5,6,7,8-四氢萘-2-醇的中间体，可用于治疗骨质疏松症。