公开(公告)号：US08501967B2

公开(公告)日：2013-08-06

申请号：US13560621

申请日：2012-07-27

申请人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Dominique Michel

发明人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Dominique Michel

IPC分类号： C07D333/22

CPC分类号： C07C303/22 ,  C07B2200/07 ,  C07C213/02 ,  C07C221/00 ,  C07C309/04 ,  C07C309/07 ,  C07C309/30 ,  C07C215/30 ,  C07C225/16

摘要： A process for the preparation of N-monosubstituted β-aminoalcohol sulfonates of formula (1a), (1b): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues; including a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, said organic solvent which can include water to provide N-monosubstituted β-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and b) asymmetrically hydrogenating.

摘要翻译： 制备式（1a），（1b）的N-单取代的β-氨基醇磺酸盐的方法：其中R1是C6-20-芳基或C4-12 - 杂芳基，每个任选被一个或多个卤素原子和/ 或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基，R 2是C 1-4 - 烷基或C 6-20 - 芳基，每个芳基任选地被一个或多个卤素原子和/或一个或多个C 1〜 4-烷基或C 1-4 - 烷氧基，并且其中R 3选自C 1-18 - 烷基，C 6-20 - 环烷基，C 6-20 - 芳基和C 7-20 - 芳烷基残基; 包括a）使甲基酮，伯胺，甲醛和磺酸在高于1.5巴的压力下，任选地在有机溶剂中反应，所述有机溶剂可包括水以提供式（III）的N-单取代的β-氨基酮磺酸盐 II）：其中R1，R2和R3如上定义，和b）不对称氢化。

公开(公告)号：US20110207946A1

公开(公告)日：2011-08-25

申请号：US13064147

申请日：2011-03-08

申请人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

发明人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

IPC分类号： C07D333/20

CPC分类号： C07C213/00 ,  C07B2200/07 ,  C07D333/22

摘要： Provided is a process for the preparation of enantiomerically pure 1-substituted-3-aminoalcohols, particularly of (S)-(−)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of formula (II), wherein R1 is selected from the group consisting of 2-thienyl, 2-furanyl and phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein the corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Furthermore provided are salts of a carboxylic acid with said aminoketones and the aminoalcohols obtained by asymmetriacally hydrogenating said aminoketones, respectively.

摘要翻译： 提供了制备对映体纯的1-取代-3-氨基醇，特别是（S） - （ - ） - 和（R） - （+） - 3-N-甲基氨基-1-（2-噻吩基） -1-丙醇，通过用式（II）的氨基酮不对称氢化羧酸盐，其中R 1选自2-噻吩基，2-呋喃基和苯基，每个任选被一个或多个卤素原子取代 和/或一个或多个C 1-4 - 烷氧基，并且其中R 2是C 1-4 - 烷基或苯基，各自任选被一个或多个卤素原子和/或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基，并且其中相应的氨基醇通过其盐的随后水解获得。 此外，还提供了羧酸与所述氨基酮和通过不对称地氢化所述氨基酮而获得的氨基醇的盐。

公开(公告)号：US20120316350A1

公开(公告)日：2012-12-13

申请号：US13560621

申请日：2012-07-27

申请人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Dominique Michel

发明人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Dominique Michel

IPC分类号： C07D333/22 ,  C07C309/04

CPC分类号： C07C303/22 ,  C07B2200/07 ,  C07C213/02 ,  C07C221/00 ,  C07C309/04 ,  C07C309/07 ,  C07C309/30 ,  C07C215/30 ,  C07C225/16

摘要： A process for the preparation of N-monosubstituted β-aminoalcohol sulfonates of formula (1a), (1b): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues; including a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, said organic solvent which can include water to provide N-monosubstituted β-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and b) asymmetrically hydrogenating.

摘要翻译： 一种制备式（1a），（1b）的N-单取代的 - 氨基醇磺酸盐的方法：其中R1是C6-20-芳基或C4-12 - 杂芳基，每个任选被一个或多个卤素原子取代， /或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基，R 2是C 1-4 - 烷基或C 6-20 - 芳基，每个芳基任选被一个或多个卤素原子和/或一个或多个C 1 4-烷基或C 1-4 - 烷氧基，其中R 3选自C 1-18 - 烷基，C 6-20 - 环烷基，C 6-20 - 芳基和C 7-20 - 芳烷基残基; 包括a）使甲基酮，伯胺，甲醛和磺酸在高于1.5巴的压力下，任选地在有机溶剂中反应，所述有机溶剂可以包括水以提供具有式（I）的N-单取代和重量的氨基酮磺酸盐 （II）：其中R1，R2和R3如上定义，和b）不对称氢化。

公开(公告)号：US07973182B2

公开(公告)日：2011-07-05

申请号：US10590140

申请日：2005-02-21

申请人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

发明人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

IPC分类号： C07D307/02 ,  C07D333/20

CPC分类号： C07C213/00 ,  C07B2200/07 ,  C07D333/22

摘要： A process for the preparation of enantiomerically pure 1-substituted-3-amino-alcohols, particularly of (S)-(−)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of the formula: wherein R1 is 2-thienyl, 2-furanyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups. The corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Salts of a carboxylic acid with the aminoketones and the aminoalcohols obtained by asymmetrically hydrogenating the aminoketones, respectively.

摘要翻译： 制备对映体纯的1-取代-3-氨基醇，特别是（S） - （ - ） - 和（R） - （+） - 3-N-甲基氨基-1-（2-噻吩基） -1-丙醇，通过用下式的氨基酮不对称氢化羧酸盐：其中R1是2-噻吩基，2-呋喃基或苯基，每个任选被一个或多个卤素原子和/或一个或多个C 1〜 4-烷基或C 1-4 - 烷氧基，并且其中R 2为C 1-4 - 烷基或苯基，各自任选被一个或多个卤素原子和/或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基取代 。 相应的氨基醇通过其盐的水解得到。 羧酸与通过不对称氢化氨基酮获得的氨基酮和氨基醇的羧酸盐。

公开(公告)号：US20090156833A1

公开(公告)日：2009-06-18

申请号：US11884542

申请日：2006-02-14

申请人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Colette Mettler ,  Dominique Michel

发明人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Colette Mettler ,  Dominique Michel

IPC分类号： C07D333/36

CPC分类号： C07C303/22 ,  C07B2200/07 ,  C07C213/02 ,  C07C221/00 ,  C07C309/04 ,  C07C309/07 ,  C07C309/30 ,  C07C215/30 ,  C07C225/16

摘要： A process for the preparation of N-monosubstituted β-aminoalcohol sulfonates of formula (Ia), (Ib): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues. The process has the steps of (a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, the organic solvent optionally containing water, to afford N-monosubstituted β-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and (b) asymmetrically hydrogenating. The sulfonates in the presence of a base and a catalyst of a transition metal and a disphosphine ligand, in a polar solvent, optionally in the presence of water.

摘要翻译： 制备式（Ia），（Ib）的N-单取代的β-氨基醇磺酸盐的方法：其中R1是C6-20-芳基或C4-12 - 杂芳基，每个任选被一个或多个卤素原子和/ 或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基，R 2是C 1-4 - 烷基或C 6-20 - 芳基，每个芳基任选地被一个或多个卤素原子和/或一个或多个C 1〜 4-烷基或C 1-4 - 烷氧基，并且其中R 3选自C 1-18 - 烷基，C 6-20 - 环烷基，C 6-20 - 芳基和C 7-20 - 芳烷基残基。 该方法具有以下步骤：（a）使甲基酮，伯胺，甲醛和磺酸在高于1.5巴的压力下，任选地在有机溶剂（任选含有水的有机溶剂）中反应，得到N-单取代的β （II）的氨基酮磺酸盐：其中R1，R2和R3如上定义，和（b）不对称氢化。 在极性溶剂中，任选地在水存在下，在过渡金属和二膦配体的碱存在下和催化剂存在下的磺酸盐。

公开(公告)号：US08258338B2

公开(公告)日：2012-09-04

申请号：US11884542

申请日：2006-02-14

申请人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Colette Mettler, legal representative ,  Dominique Michel

发明人： Walter Brieden ,  Martin Clausen ,  John McGarrity ,  Hanspeter Mettler ,  Dominique Michel

IPC分类号： C07C33/32 ,  C07D333/12

CPC分类号： C07C303/22 ,  C07B2200/07 ,  C07C213/02 ,  C07C221/00 ,  C07C309/04 ,  C07C309/07 ,  C07C309/30 ,  C07C215/30 ,  C07C225/16

摘要： A process for the preparation of N-monosubstituted β-aminoalcohol sulfonates of formula (Ia), (Ib): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues. The process has the steps of (a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, the organic solvent optionally containing water, to afford N-monosubstituted β-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and (b) asymmetrically hydrogenating. The sulfonates in the presence of a base and a catalyst of a transition metal and a disphosphine ligand, in a polar solvent, optionally in the presence of water.

摘要翻译： 一种制备式（Ia），（Ib）的N-单取代和（bgr） - 氨基醇磺酸盐的方法：其中R1是C6-20-芳基或C4-12 - 杂芳基，各自任选被一个或多个卤素原子取代， /或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基，R 2是C 1-4 - 烷基或C 6-20 - 芳基，每个芳基任选被一个或多个卤素原子和/或一个或多个C 1 -4-烷基或C 1-4 - 烷氧基，并且其中R 3选自C 1-18 - 烷基，C 6-20 - 环烷基，C 6-20 - 芳基和C 7-20 - 芳烷基残基。 该方法具有以下步骤：（a）使甲基酮，伯胺，甲醛和磺酸在高于1.5巴的压力下，任选地在有机溶剂（任选含有水的有机溶剂）中反应，得到N-单取代的＆bgr （II）的氨基酮磺酸盐：其中R 1，R 2和R 3如上所定义，和（b）不对称氢化。 在极性溶剂中，任选地在水存在下，在过渡金属和二膦配体的碱存在下和催化剂存在下的磺酸盐。

公开(公告)号：US08198468B2

公开(公告)日：2012-06-12

申请号：US13064146

申请日：2011-03-08

申请人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

发明人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

IPC分类号： C07D307/46

CPC分类号： C07C213/00 ,  C07B2200/07 ,  C07D333/22

摘要： A salt of a carboxylic acid with an aminoketone of formula II.

摘要翻译： 羧酸与式II的氨基酮的盐。

公开(公告)号：US08193380B2

公开(公告)日：2012-06-05

申请号：US13064147

申请日：2011-03-08

申请人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

发明人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

IPC分类号： C07D307/42

CPC分类号： C07C213/00 ,  C07B2200/07 ,  C07D333/22

摘要： A salt of a carboxylic acid with an aminoalcohol of formula I.

摘要翻译： 羧酸与式I的氨基醇的盐。

公开(公告)号：US20110207945A1

公开(公告)日：2011-08-25

申请号：US13064146

申请日：2011-03-08

申请人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

发明人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

IPC分类号： C07D333/22

CPC分类号： C07C213/00 ,  C07B2200/07 ,  C07D333/22

摘要： Provided is a process for the preparation of enantiomerically pure 1-substituted-3-aminoalcohols, particularly of (S)-(−)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of formula (II), wherein R1 is selected from the group consisting of 2-thienyl, 2-furanyl and phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein the corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Furthermore provided are salts of a carboxylic acid with said aminoketones and the aminoalcohols obtained by asymmetrically hydrogenating said aminoketones, respectively.

摘要翻译： 提供了制备对映体纯的1-取代-3-氨基醇，特别是（S） - （ - ） - 和（R） - （+） - 3-N-甲基氨基-1-（2-噻吩基） -1-丙醇，通过用式（II）的氨基酮不对称氢化羧酸盐，其中R 1选自2-噻吩基，2-呋喃基和苯基，每个任选被一个或多个卤素原子取代 和/或一个或多个C 1-4 - 烷氧基，并且其中R 2是C 1-4 - 烷基或苯基，各自任选被一个或多个卤素原子和/或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基，并且其中相应的氨基醇通过其盐的随后水解获得。 此外还提供了羧酸与所述氨基酮和通过不对称氢化所述氨基酮而获得的氨基醇的盐。

公开(公告)号：US20080154047A1

公开(公告)日：2008-06-26

申请号：US10590140

申请日：2005-02-21

申请人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

发明人： Dominique Michel ,  Hanspeter Mettler ,  John McGarrity

IPC分类号： C07D333/02

CPC分类号： C07C213/00 ,  C07B2200/07 ,  C07D333/22

摘要： A process for the preparation of enantiomerically pure 1-substituted-3-amino-alcohols, particularly of (S)-(−)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of the formula: wherein R1 is 2-thienyl, 2-furanyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups. The corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Salts of a carboxylic acid with the aminoketones and the aminoalcohols obtained by asymmetrically hydrogenating the aminoketones, respectively.

摘要翻译： 制备对映体纯的1-取代-3-氨基醇，特别是（S） - （ - ） - 和（R） - （+） - 3-N-甲基氨基-1-（2-噻吩基） -1-丙醇，通过用下式的氨基酮不对称氢化羧酸盐：其中R 1是2-噻吩基，2-呋喃基或苯基，每个任选被一个或多个卤素原子取代 和/或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基，并且其中R 2是C