公开(公告)号：WO2008080992A3

公开(公告)日：2008-09-18

申请号：PCT/EP2007064647

申请日：2007-12-28

申请人： KALVINSH IVARS ,  CHERNOBROVIJS ALEKSANDRS ,  TRIBULOVICH VYACHESLAV ,  LABEISH VLADIMIR

发明人： KALVINSH IVARS ,  CHERNOBROVIJS ALEKSANDRS ,  TRIBULOVICH VYACHESLAV ,  LABEISH VLADIMIR

IPC分类号： C07C51/09 ,  C07C65/26 ,  C07C67/343 ,  C07C69/00 ,  C07F5/02

CPC分类号： C07C67/343 ,  C07C51/09 ,  C07C2603/74 ,  C07C65/26 ,  C07C69/94

摘要： A process for preparation of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid from 2-(1-adamantyl)-4-bromanisolee is disclosed, based on transformation of 2-(1-adamantyl)-4-bromanisole into a Grignard's reagent by using metallic magnesium, anhydrous lithium chloride and dibromoethane followed by transmetallation with borates to 3-(adamantyl)-4-methoxyphenylboronic acid, wich is converted into 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid esters by Suzuki-Miyaura cross-coupling reaction with alkyl-6-halonaftoates catalyzed by Pd [0] or Pd/phosphine ligands and followed by basic hydrolysis in ethylene glycol or 1,2-propanediol of ester thus obtained into 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid.

摘要翻译： 公开了从2-（1-金刚烷基）-4-溴苯甲醚制备6- [3-（1-金刚烷基）-4-甲氧基苯基] -2-萘甲酸的方法，基于2-（1-金刚烷基） ）-4-溴苯甲醚通过使用金属镁，无水氯化锂和二溴乙烷转化成格利雅试剂，然后与硼酸盐转化成3-（金刚烷基）-4-甲氧基苯基硼酸，转化为6- [3-（1-金刚烷基） -4-甲氧基苯基] -2-萘甲酸酯，通过Suzuki-Miyaura交叉偶联反应与Pd [0]或Pd /膦配体催化的烷基-6-卤代沸石反应，随后在乙二醇或1,2-丙二醇中碱性水解 的酯，由此得到6- [3-（1-金刚烷基）-4-甲氧基苯基] -2-萘甲酸。

公开(公告)号：WO2008086942A3

公开(公告)日：2008-11-06

申请号：PCT/EP2007064643

申请日：2007-12-28

申请人： KALVINSH IVARS ,  CHERNOBROVIJS ALEKSANDRS ,  TRIBULOVICH VYACHESLAV ,  LABEISH VLADIMIR

发明人： KALVINSH IVARS ,  CHERNOBROVIJS ALEKSANDRS ,  TRIBULOVICH VYACHESLAV ,  LABEISH VLADIMIR

IPC分类号： C07C51/09 ,  C07C65/26 ,  C07C67/343 ,  C07C69/00 ,  C07F5/02

CPC分类号： C07C67/343 ,  C07C51/09 ,  C07C2603/74 ,  C07C65/26 ,  C07C69/94

摘要： A method for preparation of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid is disclosed based on " one pot" synthesis approach including a direct synthesis of boronic acid derivative from 2-(1-adamantyl)-4-bromoanisole and cycloboranes with a subsequent Suzuki-Miyaura coupling with 6-halonaphtenoates and basic hydrolysis of the reaction product in ethylene glycol or 1,2-propanediol.

摘要翻译： 基于包括直接合成硼酸衍生物的一锅法合成方法公开了制备6- [3-（1-金刚烷基）-4-甲氧基苯基] -2-萘甲酸的方法 从2-（1-金刚烷基）-4-溴茴香醚和环硼烷，随后与6-卤代萘酸酯进行Suzuki-Miyaura偶联，并将反应产物在乙二醇或1,2-丙二醇中碱性水解。

公开(公告)号：WO2008086942A2

公开(公告)日：2008-07-24

申请号：PCT/EP2007/064643

申请日：2007-12-28

申请人： KALVINSH, Ivars ,  CHERNOBROVIJS, Aleksandrs ,  TRIBULOVICH, Vyacheslav ,  LABEISH, Vladimir

发明人： KALVINSH, Ivars ,  CHERNOBROVIJS, Aleksandrs ,  TRIBULOVICH, Vyacheslav ,  LABEISH, Vladimir

CPC分类号： C07C67/343 ,  C07C51/09 ,  C07C2603/74 ,  C07C65/26 ,  C07C69/94

摘要： A method for preparation of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid is disclosed based on " one pot" synthesis approach including a direct synthesis of boronic acid derivative from 2-(1-adamantyl)-4-bromoanisole and cycloboranes with a subsequent Suzuki-Miyaura coupling with 6-halonaphtenoates and basic hydrolysis of the reaction product in ethylene glycol or 1,2-propanediol.

摘要翻译： 基于“一锅”合成方法公开了制备6- [3-（1-金刚烷基）-4-甲氧基苯基] -2-萘甲酸的方法，包括直接合成硼酸衍生物 由2-（1-金刚烷基）-4-溴苯甲醚和环丁烷与随后的带有6-卤代萘醌的铃木 - 宫a偶联和乙二醇或1,2-丙二醇中的反应产物的碱性水解。

公开(公告)号：WO2008080993A2

公开(公告)日：2008-07-10

申请号：PCT/EP2007/064648

申请日：2007-12-28

申请人： KALVINSH, Ivars ,  TRIBULOVICH, Vyacheslav ,  LABEISH, Vladimir ,  CHERNOBROVIJS, Aleksandrs

发明人： KALVINSH, Ivars ,  TRIBULOVICH, Vyacheslav ,  LABEISH, Vladimir ,  CHERNOBROVIJS, Aleksandrs

CPC分类号： C07F3/02

摘要： The present invention concerns fine organic synthesis, particularly the method for preparing of substituted adamantylarylmagnesium halides. The known methods for preparing Ghgnard's reagent from substituted adamantylarylhalide give very low yeld of the desired product. Substituted adamantylarylhalides are active intermediates that by interacting with various electrophiles provide for a wide range of biologically active compounds. The aim of current invention was to develop a method for preparing substituted adamantylarylmagnesium halides. The aim was attained adding lithium chloride in the Grignard's reagent synthesis by acting on magnesium metal in dry tetrahydrofuran under argon by substituted adamantylarylhalide. It was demonstrated that adding lithium chloride to adamantylarylhalide within a range from 1:1 to 1:2 provides for stable high yield of the desired end product.

摘要翻译： 本发明涉及精细的有机合成，特别是制备取代的金刚烷基芳基卤化镁的方法。 从取代的金刚烷基卤化物制备Ghgnard试剂的已知方法给出所需产物的非常低的量。 取代的金刚烷基卤化物是通过与各种亲电试剂相互作用提供广泛范围的生物活性化合物的活性中间体。 本发明的目的是开发一种制备取代的金刚烷基芳基卤化镁的方法。 目的是通过在氩气下通过取代的金刚烷基芳基卤化物在无水四氢呋喃中作用于镁金属，在格氏试剂合成中加入氯化锂。 证明在1：1至1：2的范围内将氯化锂加入到金刚烷基卤化物中可提供所需最终产物的稳定高产率。

公开(公告)号：WO2008080993A3

公开(公告)日：2009-03-12

申请号：PCT/EP2007064648

申请日：2007-12-28

申请人： KALVINSH IVARS ,  TRIBULOVICH VYACHESLAV ,  LABEISH VLADIMIR ,  CHERNOBROVIJS ALEKSANDRS

发明人： KALVINSH IVARS ,  TRIBULOVICH VYACHESLAV ,  LABEISH VLADIMIR ,  CHERNOBROVIJS ALEKSANDRS

IPC分类号： C07F3/02

CPC分类号： C07F3/02

摘要： The present invention concerns fine organic synthesis, particularly the method for preparing of substituted adamantylarylmagnesium halides. The known methods for preparing Grignard's reagent from substituted adamantylarylhalide give very low yeld of the desired product. Substituted adamantylarylhalides are active intermediates that by interacting with various electrophiles provide for a wide range of biologically active compounds. The aim of current invention was to develop a method for preparing substituted adamantylarylmagnesium halides. The aim was attained adding lithium chloride in the Grignard's reagent synthesis by acting on magnesium metal in dry tetrahydrofuran under argon by substituted adamantylarylhalide. It was demonstrated that adding lithium chloride to adamantylarylhalide within a range from 1:1 to 1:2 provides for stable high yield of the desired end product.

摘要翻译： 本发明涉及精细的有机合成，特别是制备取代的金刚烷基芳基卤化镁的方法。 从取代的金刚烷基卤化物制备格氏试剂的已知方法给出了所需产物的非常低的量。 取代的金刚烷基卤化物是通过与各种亲电试剂相互作用提供广泛范围的生物活性化合物的活性中间体。 本发明的目的是开发一种制备取代的金刚烷基芳基卤化镁的方法。 目的是通过在氩气下通过取代的金刚烷基芳基卤化物在无水四氢呋喃中作用于镁金属，在格氏试剂合成中加入氯化锂。 证明在1：1至1：2的范围内将氯化锂加入到金刚烷基卤化物中可提供所需最终产物的稳定高产率。

公开(公告)号：WO2008080992A2

公开(公告)日：2008-07-10

申请号：PCT/EP2007/064647

申请日：2007-12-28

申请人： KALVINSH, Ivars ,  CHERNOBROVIJS, Aleksandrs ,  TRIBULOVICH, Vyacheslav ,  LABEISH, Vladimir

发明人： KALVINSH, Ivars ,  CHERNOBROVIJS, Aleksandrs ,  TRIBULOVICH, Vyacheslav ,  LABEISH, Vladimir

CPC分类号： C07C67/343 ,  C07C51/09 ,  C07C2603/74 ,  C07C65/26 ,  C07C69/94

摘要： A process for preparation of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid from 2-(1-adamantyl)-4-bromanisolee is disclosed, based on transformation of 2-(1-adamantyl)-4-bromanisole into a Grignard's reagent by using metallic magnesium, anhydrous lithium chloride and dibromoethane followed by transmetallation with borates to 3-(adamantyl)-4-methoxyphenylboronic acid, wich is converted into 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid esters by Suzuki-Miyaura cross-coupling reaction with alkyl-6-halonaftoates catalyzed by Pd [0] or Pd/phosphine ligands and followed by basic hydrolysis in ethylene glycol or 1,2-propanediol of ester thus obtained into 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid.

摘要翻译： 从2-（1-金刚烷基）-4-溴胸苷酸制备6- [3-（1-金刚烷基）-4-甲氧基苯基] -2-萘甲酸的方法公开于，基于 通过使用金属镁，无水氯化锂和二溴乙烷将2-（1-金刚烷基）-4-溴甲茴香醚转化为格氏试剂，然后用硼酸酯转化为3-（金刚烷基）-4-甲氧基苯基硼酸，将其转化成6- 通过与Pd [0]或Pd /膦配体催化的烷基-6-卤代芴酯通过Suzuki-Miyaura交叉偶联反应形成[3-（1-金刚烷基）-4-甲氧基苯基] -2-萘甲酸酯，然后在 乙二醇或1,2-丙二醇酯转化为6- [3-（1-金刚烷基）-4-甲氧基苯基] -2-萘甲酸。