公开(公告)号：US08436181B2

公开(公告)日：2013-05-07

申请号：US12676301

申请日：2008-09-02

申请人： Takeshi Ohkuma ,  Noriyoshi Arai ,  Masaya Akashi ,  Hirohito Oooka ,  Tsutomu Inoue

发明人： Takeshi Ohkuma ,  Noriyoshi Arai ,  Masaya Akashi ,  Hirohito Oooka ,  Tsutomu Inoue

IPC分类号： A61K31/44 ,  C07D453/02

CPC分类号： C07D453/02 ,  B01J31/1805 ,  B01J31/2409 ,  B01J2231/643 ,  B01J2531/0266 ,  B01J2531/821 ,  C07B53/00

摘要： A process is provided for efficiently producing an optically active 3-quinuclidinol derivative of high optical purity using a readily available ruthenium compound as an asymmetric reduction catalyst. This process is a process for producing an optically active 3-quinuclidinol derivative represented by the following formula (III) comprising asymmetrically hydrogenating a 3-quinuclidinone derivative represented by the following formula (I) in the presence of a ruthenium compound (II) represented by formula (II): Ru(X)(Y)(Px)n[R1R2C*(NR3R4)-A-R5R6C*(NR7R8)] (in the formulas, R represents a hydrogen atom or C7 to C18 aralkyl group and the like, X and Y represent hydrogen atoms or halogen atoms and the like, Px represents a phosphine ligand, n represents 1 or 2, R1 to R8 represent hydrogen atoms or C1 to C20 alkyl groups and the like, * represents an optically active carbon atom and A represents an ethylene group and the like).

摘要翻译： 提供了使用容易获得的钌化合物作为不对称还原催化剂有效地制备高光学纯度的光学活性的3-奎宁环醇衍生物的方法。 该方法是制备由下式（III）表示的光学活性3-奎宁环醇衍生物的方法，包括在下述式（I）表示的钌化合物（II）的存在下，使下式（I）表示的3-奎宁环酮衍生物 式（II）：Ru（X）（Y）（Px）n [R1R2C *（NR3R4）-A-R5R6C *（NR7R8）]（式中，R表示氢原子或C7〜C18芳烷基等 ，X和Y表示氢原子或卤素原子等，Px表示膦配体，n表示1或2，R1〜R8表示氢原子或C1〜C20烷基等，*表示光学活性碳原子， A表示亚乙基等）。

公开(公告)号：US20090259045A1

公开(公告)日：2009-10-15

申请号：US12311016

申请日：2007-10-10

申请人： Hirohito Oooka ,  Shinya Fukuhara

发明人： Hirohito Oooka ,  Shinya Fukuhara

IPC分类号： C07D221/02

CPC分类号： C07D221/22 ,  C07D221/24

摘要： The object is to produce an azabicycloalkanol derivative, particularly a cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative which is a useful intermediate for agricultural chemicals or pharmaceutical agents, with a good yield and at an industrially low cost. A diastereomer of an azabicyclo-C6-10-alkanol derivative having a methyne substituted a hydroxyl group as an asymmetric carbon (e.g., a trans-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative) is isomerized in the presence of a transition metal complex, thereby producing an excess amount of a thermodynamically more stable one of diastereomers (e.g., a cis-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative). In this manner, a thermodynamically more stable one of diastereomers of the azabicyclo-C6-10-alkanol derivatives can be produced.

摘要翻译： 本发明的目的是制备氮杂双链烷醇衍生物，特别是作为农药或药剂的有用中间体的顺式-3-取代-3-氮杂双环[3.2.1]辛-8-醇衍生物，其产率高， 工业成本低。 具有取代羟基作为不对称碳的甲炔的氮杂双环C 6-10链烷醇衍生物的非对映体（例如，反式-3-取代-3-氮杂双环[3.2.1] -8-醇衍生物）异构化为 过渡金属络合物的存在，从而产生过量的热力学上更稳定的非对映异构体（例如，顺式-3-取代-3-氮杂双环[3.2.1] -8-醇衍生物）。 以这种方式，可以制备氮杂双环C 6-10链烷醇衍生物的非对映异构体的热力学上更稳定的一种。

公开(公告)号：US08188286B2

公开(公告)日：2012-05-29

申请号：US12311016

申请日：2007-10-10

申请人： Hirohito Oooka ,  Shinya Fukuhara

发明人： Hirohito Oooka ,  Shinya Fukuhara

IPC分类号： C07D221/02

CPC分类号： C07D221/22 ,  C07D221/24

摘要： The object is to produce an azabicycloalkanol derivative, particularly a cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative which is a useful intermediate for agricultural chemicals or pharmaceutical agents, with a good yield and at an industrially low cost. A diastereomer of an azabicyclo-C6-10-alkanol derivative having a methyne substituted a hydroxyl group as an asymmetric carbon (e.g., a trans-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative) is isomerized in the presence of a transition metal complex, thereby producing an excess amount of a thermodynamically more stable one of diastereomers (e.g., a cis-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative). In this manner, a thermodynamically more stable one of diastereomers of the azabicyclo-C6-10-alkanol derivatives can be produced.

摘要翻译： 本发明的目的是制备氮杂双链烷醇衍生物，特别是作为农药或药剂的有用中间体的顺式-3-取代-3-氮杂双环[3.2.1]辛-8-醇衍生物，其产率高， 工业成本低。 具有取代羟基作为不对称碳的甲炔的氮杂双环C 6-10链烷醇衍生物的非对映体（例如，反式-3-取代-3-氮杂双环[3.2.1] -8-醇衍生物）异构化为 过渡金属络合物的存在，从而产生过量的热力学上更稳定的非对映异构体（例如，顺式-3-取代-3-氮杂双环[3.2.1] -8-醇衍生物）。 以这种方式，可以制备氮杂双环C 6-10链烷醇衍生物的非对映异构体的热力学上更稳定的一种。

公开(公告)号：US20100286398A1

公开(公告)日：2010-11-11

申请号：US12674326

申请日：2008-08-27

申请人： Hiroshi Hakuta ,  Tsutomu Imagawa ,  Hirohito Oooka ,  Shinya Fukuhara

发明人： Hiroshi Hakuta ,  Tsutomu Imagawa ,  Hirohito Oooka ,  Shinya Fukuhara

IPC分类号： C07D221/22

CPC分类号： C07D221/24 ,  C07B55/00

摘要： There are provided, according to the present invention, a method for producing a cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative, the method characterized in that a trans-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative or a mixture of the trans- and cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivatives is isomerized in the presence of an aluminum compound represented by a formula Al(OR1)3 (wherein R1 represents a hydrocarbon group in which a carbon atom having an oxygen atom bonded thereto is a secondary carbon atom). In the process, a ketone compound may be further added, in addition to the aluminum compound.

摘要翻译： 根据本发明，提供顺式-3-取代-3-氮杂双环[3.2.1]辛-8-醇衍生物的制备方法，其特征在于反式-3-取代-3-氮杂双环[3.2.1] 氮杂双环[3.2.1]辛-8-醇衍生物或反式和顺式-3-取代-3-氮杂双环[3.2.1]辛-8-醇衍生物的混合物在代表的铝化合物存在下异构化 通过式Al（OR1）3（其中R1表示其中键合有氧原子的碳原子是仲碳原子的烃基）。 在该方法中，除了铝化合物之外，还可以加入酮化合物。

公开(公告)号：US08461340B2

公开(公告)日：2013-06-11

申请号：US12674326

申请日：2008-08-27

申请人： Hiroshi Hakuta ,  Tsutomu Imagawa ,  Hirohito Oooka ,  Shinya Fukuhara

发明人： Hiroshi Hakuta ,  Tsutomu Imagawa ,  Hirohito Oooka ,  Shinya Fukuhara

IPC分类号： C07D221/22

CPC分类号： C07D221/24 ,  C07B55/00

摘要： There are provided, according to the present invention, a method for producing a cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative, the method characterized in that a trans-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative or a mixture of the trans- and cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivatives is isomerized in the presence of an aluminum compound represented by a formula Al(OR1)3 (wherein R1 represents a hydrocarbon group in which a carbon atom having an oxygen atom bonded thereto is a secondary carbon atom). In the process, a ketone compound may be further added, in addition to the aluminum compound.

摘要翻译： 根据本发明，提供顺式-3-取代-3-氮杂双环[3.2.1]辛-8-醇衍生物的制备方法，其特征在于反式-3-取代-3-氮杂双环[3.2.1] 氮杂双环[3.2.1]辛-8-醇衍生物或反式和顺式-3-取代-3-氮杂双环[3.2.1]辛-8-醇衍生物的混合物在代表的铝化合物存在下异构化 通过式Al（OR1）3（其中R1表示其中键合有氧原子的碳原子是仲碳原子的烃基）。 在该方法中，除了铝化合物之外，还可以加入酮化合物。

公开(公告)号：US08759524B2

公开(公告)日：2014-06-24

申请号：US13858586

申请日：2013-04-08

申请人： Takeshi Ohkuma ,  Noriyoshi Arai ,  Masaya Akashi ,  Hirohito Oooka ,  Tsutomu Inoue

发明人： Takeshi Ohkuma ,  Noriyoshi Arai ,  Masaya Akashi ,  Hirohito Oooka ,  Tsutomu Inoue

IPC分类号： C07D453/02

CPC分类号： C07D453/02 ,  B01J31/1805 ,  B01J31/2409 ,  B01J2231/643 ,  B01J2531/0266 ,  B01J2531/821 ,  C07B53/00

摘要： A process is provided for efficiently producing an optically active 3-quinuclidinol derivative of high optical purity using a readily available ruthenium compound as an asymmetric reduction catalyst. This process is a process for producing an optically active 3-quinuclidinol derivative represented by the following formula (III) comprising asymmetrically hydrogenating a 3-quinuclidinone derivative represented by the following formula (I) in the presence of a ruthenium compound (II) represented by formula (II): Ru(X)(Y)(Px)n[R1R2C*(NR3R4)-A-R5R6C*(NR7R8)] (in the formulas, R represents a hydrogen atom or C7 to C18 aralkyl group and the like, X and Y represent hydrogen atoms or halogen atoms and the like, Px represents a phosphine ligand, n represents 1 or 2, R1 to R8 represent hydrogen atoms or C1 to C20 alkyl groups and the like, * represents an optically active carbon atom and A represents an ethylene group and the like).

摘要翻译： 提供了使用容易获得的钌化合物作为不对称还原催化剂有效地制备高光学纯度的光学活性的3-奎宁环醇衍生物的方法。 该方法是制备由下式（III）表示的光学活性3-奎宁环醇衍生物的方法，包括在下述式（I）表示的钌化合物（II）的存在下，使下式（I）表示的3-奎宁环酮衍生物 式（II）：Ru（X）（Y）（Px）n [R1R2C *（NR3R4）-A-R5R6C *（NR7R8）]（式中，R表示氢原子或C7〜C18芳烷基等 ，X和Y表示氢原子或卤素原子等，Px表示膦配体，n表示1或2，R1〜R8表示氢原子或C1〜C20烷基等，*表示光学活性碳原子， A表示亚乙基等）。

公开(公告)号：US20130225824A1

公开(公告)日：2013-08-29

申请号：US13858586

申请日：2013-04-08

申请人： Takeshi OHKUMA ,  Noriyoshi ARAI ,  Masaya AKASHI ,  Hirohito OOOKA ,  Tsutomu INOUE

发明人： Takeshi OHKUMA ,  Noriyoshi ARAI ,  Masaya AKASHI ,  Hirohito OOOKA ,  Tsutomu INOUE

IPC分类号： C07D453/02

CPC分类号： C07D453/02 ,  B01J31/1805 ,  B01J31/2409 ,  B01J2231/643 ,  B01J2531/0266 ,  B01J2531/821 ,  C07B53/00

摘要： A process is provided for efficiently producing an optically active 3-quinuclidinol derivative of high optical purity using a readily available ruthenium compound as an asymmetric reduction catalyst. This process is a process for producing an optically active 3-quinuclidinol derivative represented by the following formula (III) comprising asymmetrically hydrogenating a 3-quinuclidinone derivative represented by the following formula (I) in the presence of a ruthenium compound (II) represented by formula (II): Ru(X)(Y)(Px)n[R1R2C*(NR3R4)-A-R5R6C*(NR7R8)] (in the formulas, R represents a hydrogen atom or C7 to C18 aralkyl group and the like, X and Y represent hydrogen atoms or halogen atoms and the like, Px represents a phosphine ligand, n represents 1 or 2, R1 to R8 represent hydrogen atoms or C1 to C20 alkyl groups and the like, * represents an optically active carbon atom and A represents an ethylene group and the like).

摘要翻译： 提供了使用容易获得的钌化合物作为不对称还原催化剂有效地制备高光学纯度的光学活性的3-奎宁环醇衍生物的方法。 该方法是制备由下式（III）表示的光学活性3-奎宁环醇衍生物的方法，包括在下述式（I）表示的钌化合物（II）的存在下，使下式（I）表示的3-奎宁环酮衍生物 式（II）：Ru（X）（Y）（Px）n [R1R2C *（NR3R4）-A-R5R6C *（NR7R8）]（式中，R表示氢原子或C7〜C18芳烷基等 ，X和Y表示氢原子或卤素原子等，Px表示膦配体，n表示1或2，R1〜R8表示氢原子或C1〜C20烷基等，*表示光学活性碳原子， A表示亚乙基等）。

公开(公告)号：US20120209004A1

公开(公告)日：2012-08-16

申请号：US13454558

申请日：2012-04-24

申请人： Hirohito Oooka ,  Shinya Fukuhara

发明人： Hirohito Oooka ,  Shinya Fukuhara

IPC分类号： C07D221/22

CPC分类号： C07D221/22 ,  C07D221/24

摘要： The object is to produce an azabicycloalkanol derivative, particularly a cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative which is a useful intermediate for agricultural chemicals or pharmaceutical agents, with a good yield and at an industrially low cost. A diastereomer of an azabicyclo-C6-10-alkanol derivative having a methyne substituted a hydroxyl group as an asymmetric carbon (e.g., a trans-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative) is isomerized in the presence of a transition metal complex, thereby producing an excess amount of a thermodynamically more stable one of diastereomers (e.g., a cis-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative). In this manner, a thermodynamically more stable one of diastereomers of the azabicyclo-C6-10-alkanol derivatives can be produced.

摘要翻译： 本发明的目的是制备氮杂双链烷醇衍生物，特别是作为农药或药剂的有用中间体的顺式-3-取代-3-氮杂双环[3.2.1]辛-8-醇衍生物，其产率高， 工业成本低。 具有取代羟基作为不对称碳的甲炔的氮杂双环C 6-10链烷醇衍生物的非对映体（例如，反式-3-取代-3-氮杂双环[3.2.1] -8-醇衍生物）异构化为 过渡金属络合物的存在，从而产生过量的热力学上更稳定的非对映异构体（例如，顺式-3-取代-3-氮杂双环[3.2.1] -8-醇衍生物）。 以这种方式，可以制备氮杂双环C 6-10链烷醇衍生物的非对映异构体的热力学上更稳定的一种。

公开(公告)号：US20100174081A1

公开(公告)日：2010-07-08

申请号：US12676301

申请日：2008-09-02

申请人： Takeshi Ohkuma ,  Noriyoshi Arai ,  Masaya Akashi ,  Hirohito Oooka ,  Tsutomu Inoue

发明人： Takeshi Ohkuma ,  Noriyoshi Arai ,  Masaya Akashi ,  Hirohito Oooka ,  Tsutomu Inoue

IPC分类号： C07D453/02

CPC分类号： C07D453/02 ,  B01J31/1805 ,  B01J31/2409 ,  B01J2231/643 ,  B01J2531/0266 ,  B01J2531/821 ,  C07B53/00

摘要： A process is provided for efficiently producing an optically active 3-quinuclidinol derivative of high optical purity using a readily available ruthenium compound as an asymmetric reduction catalyst. This process is a process for producing an optically active 3-quinuclidinol derivative represented by the following formula (III) comprising asymmetrically hydrogenating a 3-quinuclidinone derivative represented by the following formula (I) in the presence of a ruthenium compound (II) represented by formula (II): Ru(X)(Y)(Px)n[R1R2C*(NR3R4)-A-R5R6C*(NR7R8)] (in the formulas, R represents a hydrogen atom or C7 to C18 aralkyl group and the like, X and Y represent hydrogen atoms or halogen atoms and the like, Px represents a phosphine ligand, n represents 1 or 2, R1 to R8 represent hydrogen atoms or C1 to C20 alkyl groups and the like, * represents an optically active carbon atom and A represents an ethylene group and the like).

摘要翻译： 提供了使用容易获得的钌化合物作为不对称还原催化剂有效地制备高光学纯度的光学活性的3-奎宁环醇衍生物的方法。 该方法是制备由下式（III）表示的光学活性3-奎宁环醇衍生物的方法，包括在下述式（I）表示的钌化合物（II）的存在下，使下式（I）表示的3-奎宁环酮衍生物 式（II）：Ru（X）（Y）（Px）n [R1R2C *（NR3R4）-A-R5R6C *（NR7R8）]（式中，R表示氢原子或C7〜C18芳烷基等 ，X和Y表示氢原子或卤素原子等，Px表示膦配体，n表示1或2，R1〜R8表示氢原子或C1〜C20烷基等，*表示光学活性碳原子， A表示亚乙基等）。

公开(公告)号：US20100004455A1

公开(公告)日：2010-01-07

申请号：US12311315

申请日：2007-10-10

申请人： Hirohito Oooka ,  Yasushi Shibata ,  Hiroki Inoue ,  Tsutomu Imagawa

发明人： Hirohito Oooka ,  Yasushi Shibata ,  Hiroki Inoue ,  Tsutomu Imagawa

IPC分类号： C07D221/02

CPC分类号： C07D221/22 ,  C07D221/24 ,  C07D491/113

摘要： Provided is a method for producing a piperidin-4-one derivative useful as an intermediate for agricultural chemicals or pharmaceutical products. A piperidin-4-one derivative represented by formula (III-a) or formula (III-b) is produced by reacting a cyclic bis(aminol)ether compound represented by formula (I) and an acetone derivative represented by formula (II) in the presence of at least one substance selected from the group consisting of protonic acids, Lewis acids, acid halides and dialkyl sulfuric acids.

摘要翻译： 提供可用作农药或药品的中间体的哌啶-4-酮衍生物的制造方法。 由式（I-a）或式（III-b）表示的哌啶-4-酮衍生物通过式（I）表示的环状双（氨基醇）醚化合物与由式（II）表示的丙酮衍生物反应制备， 在至少一种选自质子酸，路易斯酸，酰卤和二烷基硫酸的物质存在下进行。