公开(公告)号：US20140243546A1

公开(公告)日：2014-08-28

申请号：US14076302

申请日：2013-11-11

Applicant: David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

Inventor： David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

IPC: C07C271/22

CPC classification number: C07D207/38 ,  C07C271/22 ,  C07D207/26 ,  C07D207/263 ,  C07D207/36 ,  C07D403/06 ,  Y02P20/55

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Abstract translation: 本发明涉及生产NEP抑制剂或其前药的新方法，特别是包含γ-氨基-δ-联苯基-α-甲基链烷酸或酸酯主链的NEP抑制剂。 具体而言，根据本发明的新方法最终涉及制备上述NEP抑制剂的中间体的合成，即根据式（1）的化合物或其盐，其中R 1和R 2各自独立地 另一个是氢或氮保护基，R3是羧基或酯基，优选羧基或烷基酯。

公开(公告)号：US20120053353A1

公开(公告)日：2012-03-01

申请号：US13216657

申请日：2011-08-24

Applicant: Werner BONRATH ,  Johannes Tschumi ,  Jonathan Medlock

Inventor： Werner BONRATH ,  Johannes Tschumi ,  Jonathan Medlock

IPC: C07D311/74 ,  C07C29/38

CPC classification number: C07C29/17 ,  C07C29/42 ,  C07C45/62 ,  C07C33/03 ,  C07C49/04 ,  C07C33/042

Abstract: The present invention is directed to a process for the manufacture of 3,7-dimethyl-1-octen-3-ol comprising the following steps: a) hydrogenation of 6-methyl-5-hepten-2-on to 6-methyl-2-heptanon in the presence of hydrogen and a palladium containing catalyst on a carrier selected from the group consisting of carbon, calcium carbonate and aluminum oxide. b) reaction of 6-methyl-2-heptanon with acetylene to 3,7-dimethyl-1-octin-3-ol in the presence of ammonia and potassium hydroxide and in the absence of any additional organic solvent; c) hydrogenation of 3,7-dimethyl-1-octin-3-ol to 3,7-dimethyl-1-octen-3-ol in the presence of hydrogen and a palladium containing catalyst on a carrier selected from the group consisting of calcium carbonate, aluminum oxide, silica, porous glass, carbon or graphite, and barium sulphate, with the proviso that the catalyst additionally contains lead when the carrier is calcium carbonate. The present invention is further directed to a process for the manufacture of isophytol and vitamin E, where a thus produced 3,7-dimethyl-1-octen-3-ol is used as starting material.

Abstract translation: 本发明涉及制备3,7-二甲基-1-辛烯-3-醇的方法，包括以下步骤：a）将6-甲基-5-庚烯-2-酮氢化成6-甲基-1-辛烯-3-醇， 在氢气和含钯催化剂的存在下，在选自碳，碳酸钙和氧化铝的载体上存在2-庚酮。 b）在氨和氢氧化钾存在下，在不存在任何另外的有机溶剂的情况下，将6-甲基-2-庚酮与乙炔反应至3,7-二甲基-1-辛烯-3-醇; c）在氢和含钯催化剂存在下，在选自以下的载体上，将3,7-二甲基-1-辛烯-3-醇氢化为3,7-二甲基-1-辛烯-3-醇： 碳酸钙，氧化铝，二氧化硅，多孔玻璃，碳或石墨和硫酸钡，条件是当载体是碳酸钙时，催化剂另外含有铅。 本发明进一步涉及一种制造异生醇和维生素E的方法，其中将如此制备的3,7-二甲基-1-辛烯-3-醇用作原料。

公开(公告)号：US20160060217A1

公开(公告)日：2016-03-03

申请号：US14939513

申请日：2015-11-12

Applicant: David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

Inventor： David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

IPC: C07D207/38 ,  C07D403/06

CPC classification number: C07D207/38 ,  C07C271/22 ,  C07D207/26 ,  C07D207/263 ,  C07D207/36 ,  C07D403/06 ,  Y02P20/55

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

公开(公告)号：US08546621B2

公开(公告)日：2013-10-01

申请号：US13216657

申请日：2011-08-24

Applicant: Werner Bonrath ,  Johannes Tschumi ,  Jonathan Medlock

Inventor： Werner Bonrath ,  Johannes Tschumi ,  Jonathan Medlock

IPC: C07C29/14 ,  C07C29/38 ,  C07D311/74

CPC classification number: C07C29/17 ,  C07C29/42 ,  C07C45/62 ,  C07C33/03 ,  C07C49/04 ,  C07C33/042

Abstract: The present invention is directed to a process for the manufacture of 3,7-dimethyl-1-octen-3-ol comprising the following steps: a) hydrogenation of 6-methyl-5-hepten-2-on to 6-methyl-2-heptanon in the presence of hydrogen and a palladium containing catalyst on a carrier selected from the group consisting of carbon, calcium carbonate and aluminum oxide. b) reaction of 6-methyl-2-heptanon with acetylene to 3,7-dimethyl-1-octin-3-ol in the presence of ammonia and potassium hydroxide and in the absence of any additional organic solvent; c) hydrogenation of 3,7-dimethyl-1-octin-3-ol to 3,7-dimethyl-1-octen-3-ol in the presence of hydrogen and a palladium containing catalyst on a carrier selected from the group consisting of calcium carbonate, aluminum oxide, silica, porous glass, carbon or graphite, and barium sulphate, with the proviso that the catalyst additionally contains lead when the carrier is calcium carbonate. The present invention is further directed to a process for the manufacture of isophytol and vitamin E, where a thus produced 3,7-dimethyl-1-octen-3-ol is used as starting material.

Abstract translation: 本发明涉及制备3,7-二甲基-1-辛烯-3-醇的方法，包括以下步骤：a）将6-甲基-5-庚烯-2-酮氢化成6-甲基-1-辛烯-3-醇， 在氢气和含钯催化剂的存在下，在选自碳，碳酸钙和氧化铝的载体上存在2-庚酮。 b）在氨和氢氧化钾存在下，在不存在任何另外的有机溶剂的情况下，将6-甲基-2-庚酮与乙炔反应至3,7-二甲基-1-辛烯-3-醇; c）在氢和含钯催化剂存在下，在选自以下的载体上，将3,7-二甲基-1-辛烯-3-醇氢化为3,7-二甲基-1-辛烯-3-醇： 碳酸钙，氧化铝，二氧化硅，多孔玻璃，碳或石墨和硫酸钡，条件是当载体是碳酸钙时，催化剂另外含有铅。 本发明进一步涉及一种制造异生醇和维生素E的方法，其中将如此制备的3,7-二甲基-1-辛烯-3-醇用作原料。

公开(公告)号：US20080081930A1

公开(公告)日：2008-04-03

申请号：US11719478

申请日：2005-11-01

Applicant: Beatriz Dominguez ,  Antonio Zanotti-Gerosa ,  Gabriela Grasa ,  Jonathan Medlock

Inventor： Beatriz Dominguez ,  Antonio Zanotti-Gerosa ,  Gabriela Grasa ,  Jonathan Medlock

IPC: C07C49/15 ,  B01J31/12 ,  C07C311/16

CPC classification number: B01J31/1805 ,  B01J2231/643 ,  B01J2531/821 ,  B01J2531/822 ,  B01J2531/824 ,  B01J2531/827 ,  B01J2531/828 ,  B01J2531/842 ,  B01J2531/845 ,  B01J2531/847 ,  C07B2200/07 ,  C07C29/143 ,  C07C311/18 ,  C07C2602/10 ,  C07C33/46 ,  C07C33/22 ,  C07C35/32

Abstract: A diamine of formula (I) is described, in which A is hydrogen or a saturated or unsaturated C1-C20 alkyl group or an aryl group; B is a substituted or unsubstituted C1-C20 alkyl, cycloalkyl, alkaryl, alkaryl or aryl group or an alkylamino group and at least one of X1, X2, Y1, Y2 or Z is a C1-C10 alkyl, cycloalkyl, alkaryl, aralkyl or alkoxy substituting group. The chiral diamine may be used to prepare catalysts suitable for use in transfer hydrogenation reactions.

Abstract translation: 描述了式（I）的二胺，其中A是氢或饱和或不饱和的C 1 -C 20烷基或芳基; B是取代或未取代的C 1 -C 20烷基，环烷基，烷芳基，烷芳基或芳基或烷基氨基，X 1，X 2， 或者Z是C1-C10烷基，环烷基，烷芳基，芳烷基或烷氧基取代基。 手性二胺可用于制备适用于转移氢化反应的催化剂。

公开(公告)号：US09403766B2

公开(公告)日：2016-08-02

申请号：US14939513

申请日：2015-11-12

Applicant: David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

Inventor： David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

IPC: C07D207/26 ,  C07D207/38 ,  C07D207/263 ,  C07D207/36 ,  C07D403/06 ,  C07C271/22

CPC classification number: C07D207/38 ,  C07C271/22 ,  C07D207/26 ,  C07D207/263 ,  C07D207/36 ,  C07D403/06 ,  Y02P20/55

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Abstract translation: 本发明涉及生产NEP抑制剂或其前药的新方法，特别是包含γ-氨基-δ-联苯基-α-甲基链烷酸或酸酯主链的NEP抑制剂。 具体而言，根据本发明的新方法最终涉及制备上述NEP抑制剂的中间体的合成，即根据式（1）的化合物或其盐，其中R 1和R 2各自独立地 另一个是氢或氮保护基，R3是羧基或酯基，优选羧基或烷基酯。

公开(公告)号：US09227934B2

公开(公告)日：2016-01-05

申请号：US14715129

申请日：2015-05-18

Applicant: David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

Inventor： David Hook ,  Bernard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

IPC: C07D207/38

CPC classification number: C07D207/38 ,  C07C271/22 ,  C07D207/26 ,  C07D207/263 ,  C07D207/36 ,  C07D403/06 ,  Y02P20/55

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

公开(公告)号：US20140249321A1

公开(公告)日：2014-09-04

申请号：US14125954

申请日：2012-06-13

Applicant: Marc-André Mueller ,  Andreas Pfaltz ,  Jonathan Medlock

Inventor： Marc-André Mueller ,  Andreas Pfaltz ,  Jonathan Medlock

IPC: C07C45/62 ,  C07C45/61 ,  C07D311/72 ,  C07C49/04 ,  C07C29/143

CPC classification number: C07C45/62 ,  C07C29/143 ,  C07C45/61 ,  C07C49/04 ,  C07D311/72

Abstract: The present invention relates in a first aspect to a process for hydrogenation of ketones having at least a carbon-carbon double bond in the y,8-position to the keto group by hydrogen in the presence of at least one chiral iridium complex of formula (I), where R1 represents a group of formula (II) or (III) or (IV). It has been shown that this process leads to a strong increase in preferential formation of a single isomer. The process is particularly suitable for the hydrogenation of y,8-unsaturated ketones which can be used as flavours and fragrances or for the preparation of vitamin E and its derivatives or of flavours and fragrances.

Abstract translation: 本发明在第一方面涉及在至少一种式（I）的手性铱络合物（式 I），其中R 1表示式（II）或（III）或（IV）的基团。 已经表明，该方法导致单一异构体的优先形成的强烈增加。 该方法特别适用于可用作香料和香料的y，8-不饱和酮的氢化，或用于制备维生素E及其衍生物或香料和香料的方法。

公开(公告)号：US08580974B2

公开(公告)日：2013-11-12

申请号：US12863213

申请日：2009-01-16

Applicant: David Hook ,  Bernhard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

Inventor： David Hook ,  Bernhard Riss ,  Daniel Kaufmann ,  Matthias Napp ,  Erhard Bappert ,  Philippe Polleux ,  Jonathan Medlock ,  Antonio Zanotti-Gerosa

IPC: C07D207/38 ,  C07D207/26

CPC classification number: C07D207/38 ,  C07C271/22 ,  C07D207/26 ,  C07D207/263 ,  C07D207/36 ,  C07D403/06 ,  Y02P20/55

Abstract: The invention relates to a new process for producing NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone. In detail, the new processes, according to the present invention, are ultimately related to the synthesis of intermediates to prepare the above NEP inhibitors, namely compounds according to formula (1), or salt thereof, wherein R1 and R2 are, independently of each other, hydrogen or a nitrogen protecting group, and R3 is a carboxyl group or an ester group, preferably carboxyl group or alkyl ester.

Abstract translation: 本发明涉及用于产生NEP抑制剂或其前药的新方法，特别是包含γ-氨基-Δ-联苯基-α-甲基链烷酸或酸酯主链的NEP抑制剂。 具体而言，根据本发明的新方法最终涉及制备上述NEP抑制剂的中间体的合成，即根据式（1）的化合物或其盐，其中R 1和R 2各自独立地 另一个是氢或氮保护基，R3是羧基或酯基，优选羧基或烷基酯。

公开(公告)号：US09181163B2

公开(公告)日：2015-11-10

申请号：US14125954

申请日：2012-06-13

Applicant: Marc-André Mueller ,  Andreas Pfaltz ,  Jonathan Medlock

Inventor： Marc-André Mueller ,  Andreas Pfaltz ,  Jonathan Medlock

IPC: C07C45/62 ,  C07C29/143 ,  C07C45/61 ,  C07C49/04 ,  C07D311/72

CPC classification number: C07C45/62 ,  C07C29/143 ,  C07C45/61 ,  C07C49/04 ,  C07D311/72

Abstract: The present invention relates in a first aspect to a process for hydrogenation of ketones having at least a carbon-carbon double bond in the y,8-position to the keto group by hydrogen in the presence of at least one chiral iridium complex of formula (I), where R1 represents a group of formula (II) or (III) or (IV). It has been shown that this process leads to a strong increase in preferential formation of a single isomer. The process is particularly suitable for the hydrogenation of y,8-unsaturated ketones which can be used as flavors and fragrances or for the preparation of vitamin E and its derivatives or of flavors and fragrances.

Abstract translation: 本发明在第一方面涉及在至少一种式（I）的手性铱络合物（式 I），其中R 1表示式（II）或（III）或（IV）的基团。 已经表明，该方法导致单一异构体优先形成的强烈增加。 该方法特别适用于可用作香料和香料的y，8-不饱和酮的氢化，或用于制备维生素E及其衍生物或香料和香料的方法。