公开(公告)号：US06566537B2

公开(公告)日：2003-05-20

申请号：US09919401

申请日：2001-07-31

申请人： Pher G. Andersson ,  Christian Hedberg

发明人： Pher G. Andersson ,  Christian Hedberg

IPC分类号： C07D31102

CPC分类号： C07D311/20 ,  C07B2200/07 ,  C07C29/143 ,  C07C35/32 ,  C07C45/512 ,  C07C45/65 ,  C07C45/74 ,  C07C49/835 ,  C07C213/00 ,  C07C213/02 ,  C07C215/54 ,  C07C2602/24 ,  C07C49/67 ,  C07C49/813

摘要： The invention relates to a process for the enantioselective preparation of tolterodine and analogues and salts thereof comprises the steps of: a) enantioselectively reducing the carbonyl function in a compound of formula (II): wherein R1, R2 and R3 independently of each other are hydrogen, methyl, methoxy, hydroxy, hydroxymethyl, carbamoyl, sulphamoyl or halogen, to form an enantiomerically enriched compound of formula (IIIa) or (IIIb): wherein R1, R2 and R3 are as defined above; b) subjecting the compound of formula (IIIa) or (IIb) to a sigmatropic rearrangement to form a corresponding enantiomerically enriched compound of formula (IVa) or (IVb): wherein R1, R2 and R3 are as defined above; c) subjecting the compound of formula (IVa) or (IVb) to a Baeyer-Villiger oxidation to form a corresponding enantiomerically enriched compound of the general formula (Va) or (Vb): wherein R1, R2 and R3 are as defined above; d) converting the compound of formula (Va) or (Vb) to form the corresponding enantiometrically enriched compound of tolterodine or analogue, and e) optionally converting a compound obtained in base form to a salt thereof, or converting a salt form to the free base. The invention also relates to novel starting materials and intermediates used in the process.

摘要翻译： 本发明涉及一种用于对映选择性制备托特罗定及其类似物及其盐的方法，包括以下步骤：a）对式（II）化合物中对映体选择性还原羰基官能团：其中R1，R2和R3彼此独立地为氢 ，甲基，甲氧基，羟基，羟甲基，氨基甲酰基，氨磺酰基或卤素，以形成对映体富集的式（IIIa）或（IIIb）化合物：其中R1，R2和R3如上定义; b） IIIa）或（IIb）化合物以形成相应的对映异构体富集的式（IVa）或（IVb）化合物：其中R 1，R 2和R 3如上所定义; c）使式（Ⅳa）化合物或（ IVb）至Baeyer-Villiger氧化反应形成通式（Ⅴa）或（Ⅴb）的相应对映异构体富集的化合物：其中R 1，R 2和R 3如上定义; d）将式（Ⅴa）化合物或（ Vb）形成相应的对应 富马酸或其类似物的富集的化合物，和）任选地将以碱形式获得的化合物转化为其盐，或将盐形式转化为游离碱。本发明还涉及在该方法中使用的新的起始原料和中间体。

公开(公告)号：US06534653B2

公开(公告)日：2003-03-18

申请号：US09828882

申请日：2001-04-10

申请人： Pher G. Andersson ,  Sofia J. M. Nordin ,  Peter Roth

发明人： Pher G. Andersson ,  Sofia J. M. Nordin ,  Peter Roth

IPC分类号： C07F702

CPC分类号： C07D491/08 ,  C07B53/00

摘要： Compounds of the formula I, in the form of their racemates, mixtures of stereoisomers or mainly pure stereoisomers in which Y is C1-C4alkylene or —SiR1R2—; X is a carbon atom and A1 and A2 independently of one another are hydrogen, C1-C12alkyl, C2-C12alkenyl, C3-C8cycloalkyl, C3-C8cycloalkenyl, C3-C8cycloalkyl-C1-C4alkyl, C3-C8cycloalkenyl-C1-C4alkyl, C6-C10aryl or C7-C14aralkyl; or X is a silicon atom and A1 and A2 independently of one another are C1-C12alkyl, C3-C8cycloalkyl, C3-C8cycloalkyl-C1-C4alkyl, C6-C10aryl or C7-C14aralkyl; A3 and A4 independently of one another are hydrogen, C1-C12alkyl, C3-C8cycloalkyl, C3-C8-cycloalkyl-C1-C4alkyl, C6-C10aryl or C7-C14aralkyl; and R1 and R2 independently of one another are C1-C6alkyl, cyclohexyl, phenyl or benzyl, are ligands for metal complexes of the eighth sub-group of the Periodic Table of the Elements, which are suitable as catalysts for asymmetric hydrogenations and transfer hydrogenations of prochiral compounds having carbon/carbon or carbon/heteroatom multiple bonds.

摘要翻译： 式I的化合物，其外消旋体的形式，立体异构体的混合物或主要为纯的立体异构体，其中Y为C1-C4亚烷基或-SiR1R2-; X为碳原子，A1和A2彼此独立地为氢，C1-C12烷基， C 2 -C 12烯基，C 3 -C 8环烷基，C 3 -C 8环烯基，C 3 -C 8环烷基-C 1 -C 4烷基，C 3 -C 8环烯基-C 1 -C 4烷基，C 6 -C 10芳基或C 7 -C 14芳烷基; or X为硅原子，且A 1和A 2彼此独立地为C 1 -C 12烷基，C 3 -C 8环烷基，C 3 -C 8环烷基-C 1 -C 4烷基，C 6 -C 10芳基或C 7 -C 14芳烷基; A 3和A 4彼此独立地为氢， C 2 -C 6烷基，C 3 -C 8环烷基，C 3 -C 8环烷基-C 1 -C 4烷基，C 6 -C 10芳基或C 7 -C 14芳烷基; 和R 1和R 2彼此独立地是C 1 -C 6烷基，环己基，苯基或苄基，是元素周期表第八子组的金属络合物的配体，其适合作为不对称氢化和前手性转移氢化的催化剂 具有碳/碳或碳/杂原子多键的化合物。

公开(公告)号：US06310248B2

公开(公告)日：2001-10-30

申请号：US09748042

申请日：2000-12-22

申请人： Pher G. Andersson ,  Christian Hedberg

发明人： Pher G. Andersson ,  Christian Hedberg

IPC分类号： C07C21100

CPC分类号： C07D311/20 ,  C07B2200/07 ,  C07C29/143 ,  C07C35/32 ,  C07C45/512 ,  C07C45/65 ,  C07C45/74 ,  C07C49/835 ,  C07C213/00 ,  C07C213/02 ,  C07C215/54 ,  C07C2602/08 ,  C07C49/67 ,  C07C49/813

摘要： The invention relates to a process for the enantioselective preparation of tolterodine and analogues and salts thereof comprises the steps of: a) enantioselectively reducing the carbonyl function in a compound of formula (II): wherein R1, R2 and R3 independently of each other are hydrogen, methyl, methoxy, hydroxy, hydroxymethyl, carbamoyl, sulphamoyl or halogen, to form an enantiomerically enriched compound of formula (IIIa) or (IIIb): wherein R1, R2 and R3 are as defined above; b) subjecting the compound of formula (IIIa) or (IIIb) to a sigmatropic rearrangement to form a corresponding enantiomerically enriched compound of formula (IVa) or (IVb): wherein R1, R2 and R3 are as defined above; c) subjecting the compound of formula (IVa) or (IVb) to a Baeyer-Virliger oxidation to form a corresponding enantiomerically enriched compound of the general formula (Va) or (Vb): wherein R1, R2 and R3 are as defined above; d) converting the compound of formula (IVa) or (IVb) to form the coresponding enantiometrically enriched compound of tolterodine or analogue, and e) optionally converting a compound obtained in base form to a salt thereof, or converting a salt form to the free base. The invention also relates to novel starting materials and intermediates use in the process.

摘要翻译： 本发明涉及一种用于对映选择性制备托特罗定及其类似物及其盐的方法，包括以下步骤：a）对式（II）化合物中对映体选择性还原羰基官能团：其中R1，R2和R3彼此独立地为氢 ，甲基，甲氧基，羟基，羟甲基，氨基甲酰基，氨磺酰基或卤素，以形成对映体富集的式（IIIa）或（IIIb）化合物：其中R1，R2和R3如上定义; b） IIIa）或（IIIb）化合物以形成相应的对映体富集的式（IVa）或（IVb）化合物：其中R 1，R 2和R 3如上所定义; c）使式（Ⅳa）化合物或（ IVb）至Baeyer-Virliger氧化反应形成通式（Ⅴa）或（Ⅴb）的相应对映体富集化合物：其中R 1，R 2和R 3如上定义; d）将式（Ⅳa）化合物或（ IVb）形成相应的对应 特异性富集的托特罗定或类似物的化合物，和）任选地将以碱形式获得的化合物转化为其盐，或将盐形式转化为游离碱。本发明还涉及在该方法中使用的新的起始材料和中间体。

公开(公告)号：US06790998B2

公开(公告)日：2004-09-14

申请号：US10402671

申请日：2003-03-28

申请人： Pher G. Andersson ,  Christian Hedberg

发明人： Pher G. Andersson ,  Christian Hedberg

IPC分类号： C07C49537

CPC分类号： C07D311/20 ,  C07B2200/07 ,  C07C29/143 ,  C07C35/32 ,  C07C45/512 ,  C07C45/65 ,  C07C45/74 ,  C07C49/835 ,  C07C213/00 ,  C07C213/02 ,  C07C215/54 ,  C07C2602/24 ,  C07C49/67 ,  C07C49/813

摘要： The invention relates to a process for the enantioselective preparation of tolterodine and analogues and salts thereof comprises the steps of: a) enantioselectively reducing the carbonyl function in a compound of formula (II): wherein R1, R2 and R3 independently of each other are hydrogen, methyl, methoxy, hydroxy, hydroxymethyl, carbamoyl, sulphamoyl or halogen, to form an enantiomerically enriched compound of formula (IIIa) or (IIIb): wherein R1, R2 and R3 are as defined above; b) subjecting the compound of formula (IIIa) or (IIIb) to a sigmatropic rearrangement to form a corresponding enantiomerically enriched compound of formula (IVa) or (IVb): wherein R1, R2 and R3 are as defined above; c) subjecting the compound of formula (IVa) or (IVb) to a Baeyer-Villiger oxidation to form a corresponding enantiomerically enriched compound of the general formula (Va) or (Vb). wherein R1, R2 and R3 are as defined above; d) converting the compound of formula (Va) or (Vb) to form the corresponding enantiometrically enriched compound of tolterodine or analogue, and e) optionally converting a compound obtained in base form to a salt thereof, or converting a salt form to the free base. The invention also relates to novel starting materials and intermediates used in the process.

摘要翻译： 本发明涉及一种用于对映选择性制备托特罗定及其类似物及其盐的方法，包括以下步骤：a）对式（II）化合物中对映体选择性还原羰基官能团：其中R1，R2和R3彼此独立地为氢 ，甲基，甲氧基，羟基，羟甲基，氨基甲酰基，氨磺酰基或卤素，以形成对映体富集的式（IIIa）或（IIIb）化合物：其中R1，R2和R3如上定义; b） IIIa）或（IIIb）化合物以形成相应的对映体富集的式（IVa）或（IVb）化合物：其中R 1，R 2和R 3如上所定义; c）使式（Ⅳa）化合物或（ （Va）或（Vb）的相应对映异构体富集的化合物，其中R 1，R 2和R 3如上所定义; d）将式（ⅤⅤ）化合物或（Ⅴb）化合物转化为 Vb）形成相应的对映体 特异度富集的托特罗定或类似物的化合物，和）任选地将以碱形式获得的化合物转化为其盐，或将盐形式转化为游离碱。本发明还涉及用于该方法的新的起始原料和中间体。

公开(公告)号：US06689916B2

公开(公告)日：2004-02-10

申请号：US10401361

申请日：2003-03-28

申请人： Pher G. Andersson ,  Christian Hedberg

发明人： Pher G. Andersson ,  Christian Hedberg

IPC分类号： C07C49794

CPC分类号： C07D311/20 ,  C07B2200/07 ,  C07C29/143 ,  C07C35/32 ,  C07C45/512 ,  C07C45/65 ,  C07C45/74 ,  C07C49/835 ,  C07C213/00 ,  C07C213/02 ,  C07C215/54 ,  C07C2602/24 ,  C07C49/67 ,  C07C49/813

摘要： The invention relates to a process for the enantioselective preparation of tolterodine and analogues and salts thereof comprises the steps of: a) enantioselectively reducing the carbonyl function in a compound of formula (II):  wherein R1, R2 and R3 independently of each other are hydrogen, methyl, methoxy, hydroxy, hydroxymethyl, carbamoyl, sulphamoyl or halogen, to form an enantiomerically enriched compound of formula (IIIa) or (IIIb):  wherein R1, R2 and R3 are as defined above; b) subjecting the compound of formula (IIIa) or (IIIb) to a sigmatropic rearrangement to form a corresponding enantiomerically enriched compound of formula (IVa) or (IVb):  wherein R1, R2 and R3 are as defined above; c) subjecting the compound of formula (IVa) or (IVb) to a Baeyer-Villiger oxidation to form a corresponding enantiomerically enriched compound of the general formula (Va) or (Vb): wherein R1, R2 and R3 are as defined above; d) converting the compound of formula (Va) or (Vb) to form the corresponding enantiometrically enriched compound of tolterodine or analogue, and e) optionally converting a compound obtained in base form to a salt thereof, or converting a salt form to the free base. The invention also relates to novel starting materials and intermediates used in the process.

摘要翻译： 本发明涉及一种用于对映选择性制备托特罗定及其类似物及其盐的方法，包括以下步骤：a）对式（II）化合物中对映体选择性还原羰基官能团：其中R1，R2和R3彼此独立地为氢 ，甲基，甲氧基，羟基，羟甲基，氨基甲酰基，氨磺酰基或卤素，以形成对映体富集的式（IIIa）或（IIIb）化合物：其中R1，R2和R3如上定义; b） IIIa）或（IIIb）化合物以形成相应的对映体富集的式（IVa）或（IVb）化合物：其中R 1，R 2和R 3如上所定义; c）使式（Ⅳa）化合物或（ IVb）至Baeyer-Villiger氧化反应形成通式（Ⅴa）或（Ⅴb）的相应对映异构体富集的化合物：其中R 1，R 2和R 3如上定义; d）将式（Ⅴa）化合物或（ Vb）形成相应的对映体 特异度富集的托特罗定或类似物的化合物，和）任选地将以碱形式获得的化合物转化为其盐，或将盐形式转化为游离碱。本发明还涉及用于该方法的新的起始原料和中间体。