公开(公告)号：US20060149098A1

公开(公告)日：2006-07-06

申请号：US11276306

申请日：2006-02-23

Applicant: Masafumi FUKAE ,  Yoshiro Hiraishi

Inventor： Masafumi FUKAE ,  Yoshiro Hiraishi

IPC: C07C61/12

CPC classification number: C07C51/02 ,  C07C51/43 ,  C07C2602/28 ,  C07C59/46

Abstract: The invention aims at producing high-purity crystals of a hydroxycarboxylic acid represented by the following formula (1): in high yield. Provided are a method for crystallization of a compound (1) which comprises acidifying a mixture of a solution of an alkali salt of the compound (1) and an organic solvent, and a method for crystallization of compound (1) by mixing a solution of the compound (1) in a water-miscible good solvent with water, in which a slurry with a necessary suspension amount of the compound (1) for inhibiting oil formation and scaling is prepared in advance and then a main crystallization is carried out in the presence of said slurry.

Abstract translation: 本发明旨在以高产率制备由下式（1）表示的羟基羧酸的高纯度晶体。 提供化合物（1）的结晶方法，其包括酸化化合物（1）的碱金属盐和有机溶剂的溶液的混合物，以及通过将化合物（1）的溶液 将与化合物（1）在水混溶性好的溶剂中与水一起预先制备具有用于抑制油形成和结垢的化合物（1）所需悬浮液量的浆料，然后进行主结晶 所述浆料的存在。

公开(公告)号：US08232389B2

公开(公告)日：2012-07-31

申请号：US12308413

申请日：2007-06-13

Applicant: Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

Inventor： Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

IPC: C07F7/18

CPC classification number: C07F7/1804

Abstract: The present invention relates to a method for crystallization of (2R)-2-{(3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxoazetidin-4-yl}propionic acid, and is characterized in that crystallization is carried out by mixing a solution containing the compound with a substituted aromatic hydrocarbon solvent and/or a halogenated hydrocarbon solvent. The method can provide a crystal of the compound with a high purity and a high yield while the content of 2S isomer is kept at a low level.

Abstract translation: 本发明涉及（2R）-2 - {（3S，4S）-3 - [（1R）-1-（叔丁基二甲基甲硅烷氧基）乙基] -2-氧代氮杂环丁烷-4-基}丙酸 其特征在于，通过将含有该化合物的溶液与取代的芳烃溶剂和/或卤代烃溶剂混合来进行结晶。 该方法可以提供具有高纯度和高产率的化合物的晶体，而2S异构体的含量保持在低水平。

公开(公告)号：US07323592B2

公开(公告)日：2008-01-29

申请号：US11276306

申请日：2006-02-23

Applicant: Masafumi Fukae ,  Yoshiro Hiraishi

Inventor： Masafumi Fukae ,  Yoshiro Hiraishi

IPC: C07C61/12

CPC classification number: C07C51/02 ,  C07C51/43 ,  C07C2602/28 ,  C07C59/46

Abstract: The invention aims at producing high-purity crystals of a hydroxycarboxylic acid represented by the following formula (1): in high yield. Provided are a method for crystallization of a compound (1) which comprises acidifying a mixture of a solution of an alkali salt of the compound (1) and an organic solvent, and a method for crystallization of compound (1) by mixing a solution of the compound (1) in a water-miscible good solvent with water, in which a slurry with a necessary suspension amount of the compound (1) for inhibiting oil formation and scaling is prepared in advance and then a main crystallization is carried out in the presence of said slurry.

Abstract translation: 本发明旨在以高产率制备由下式（1）表示的羟基羧酸的高纯度晶体。 提供化合物（1）的结晶方法，其包括酸化化合物（1）的碱金属盐和有机溶剂的溶液的混合物，以及通过将化合物（1）的溶液 将与化合物（1）在水混溶性好的溶剂中与水一起预先制备具有用于抑制油形成和结垢的化合物（1）所需悬浮液量的浆料，然后进行主结晶 所述浆料的存在。

公开(公告)号：US08093378B2

公开(公告)日：2012-01-10

申请号：US12226771

申请日：2007-04-18

Applicant: Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

Inventor： Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

IPC: C07F9/568

CPC classification number: C07F9/65611 ,  C07D477/18

Abstract: An improved crystallization method for an azetidinone compound represented by the formula 1: , which is extremely useful as a common intermediate for the synthesis of 1β-methylcarbapenem compounds. The present method provides crystals having higher quality and stability than conventional crystals and excellent filterability at the time of recovery; and an azetidinone compound having a low content of impurity, and which has a controlled particle size distribution of crystals and improved handleability and stability. The crystallization is carried out by adding a hydrocarbon solvent to a solution in which an azetidinone compound extremely useful as a common intermediate for the synthesis of 1β-methylcarbapenem compounds is dissolved in the presence of a seed crystal in an amount of 200% by weight or less based on the weight of the azetidinone compound.

Abstract translation: 用于由式1表示的氮杂环丁酮化合物的改进的结晶方法：其作为合成1'-溴代 - 甲基碳青霉烯化合物的常用中间体非常有用。 本方法提供比常规晶体更高的质量和稳定性的晶体，并且在回收时具有优异的过滤性; 和具有低杂质含量的氮杂环丁酮化合物，其具有可控的晶体粒度分布和改进的可操作性和稳定性。 结晶是通过将烃溶剂加入到其中作为合成1'-溴代 - 碳代青霉烯化合物的常用中间体的氮杂环丁酮化合物在种子存在下溶解200重量％的溶液 或更少，基于氮杂环丁酮化合物的重量。

公开(公告)号：US20100298556A1

公开(公告)日：2010-11-25

申请号：US12308413

申请日：2007-06-13

Applicant: Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

Inventor： Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

IPC: C07D205/04

CPC classification number: C07F7/1804

Abstract: The present invention relates to a method for crystallization of (2R)-2-{(3S, 4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxoazetidin-4-yl}propionic acid, and is characterized in that crystallization is carried out by mixing a solution containing the compound with a substituted aromatic hydrocarbon solvent and/or a halogenated hydrocarbon solvent. The method can provide a crystal of the compound with a high purity and a high yield while the content of 2S isomer is kept at a low level.

Abstract translation: 本发明涉及（2R）-2 - {（3S，4S）-3 - [（1R）-1-（叔丁基二甲基甲硅烷氧基）乙基] -2-氧代氮杂环丁烷-4-基}丙酸 其特征在于，通过将含有该化合物的溶液与取代的芳烃溶剂和/或卤代烃溶剂混合来进行结晶。 该方法可以提供具有高纯度和高产率的化合物的晶体，而2S异构体的含量保持在低水平。

公开(公告)号：US20090118496A1

公开(公告)日：2009-05-07

申请号：US12226771

申请日：2007-04-18

Applicant: Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

Inventor： Keita Nishino ,  Teruyoshi Koga ,  Masafumi Fukae ,  Yasuyoshi Ueda

IPC: C07D487/04

CPC classification number: C07F9/65611 ,  C07D477/18

Abstract: The present invention relates to an azetidinone compound extremely useful as a common intermediate for the synthesis of 1β-methylcarbapenem compounds. The present invention provides a crystallization method to obtain a crystal which has a higher quality and a higher stability than a conventional crystal and is excellent in filterability at the time of recovering crystal; an azetidinone compound having a low content of impurity; and an azetidinone compound which has a controlled particle size distribution of crystals and improved handleability and stability. The crystallization is carried out by adding a hydrocarbon solvent to a solution in which an azetidinone compound extremely useful as a common intermediate for the synthesis of 1β-methylcarbapenem compounds is dissolved in the presence of a seed crystal in an amount of 200% by weight or less based on the weight of the azetidinone compound. According to the method, the crystal having a high quality and a high stability and excellent filterability at the time of recovering the crystal can be obtained.

Abstract translation: 本发明涉及作为合成1'-甲基碳青霉烯化合物的常用中间体非常有用的氮杂环丁酮化合物。 本发明提供一种获得具有比常规晶体更高质量和更高稳定性的晶体的结晶方法，并且在回收晶体时的过滤性优异; 具有低杂质含量的氮杂环丁酮化合物; 和具有可控的晶体粒度分布和改进的可操作性和稳定性的氮杂环丁酮化合物。 结晶是通过将烃溶剂加入到其中作为合成1,1-甲基碳青霉烯化合物的常用中间体非常有用的氮杂环丁酮化合物在200重量％的种子晶种存在下溶解的溶液进行的，或 少于氮杂环丁酮化合物的重量。 根据该方法，可以获得在回收晶体时具有高质量和高稳定性以及优异的过滤性的晶体。

公开(公告)号：US20050075508A1

公开(公告)日：2005-04-07

申请号：US10362460

申请日：2001-09-07

Applicant: Masafumi Fukae ,  Yoshiro Hiraishi

Inventor： Masafumi Fukae ,  Yoshiro Hiraishi

IPC: C07C51/02 ,  C07C51/43 ,  C07D309/30

CPC classification number: C07C51/02 ,  C07C51/43 ,  C07C2602/28 ,  C07C59/46

Abstract: The invention aims at producing high-purity crystals of a hydroxycarboxylic acid represented by the following formula (1): in high yield. Provided are a method for crystallization of a compound (1) which comprises acidifying a mixture of a solution of an alkali salt of the compound (1) and an organic solvent, and a method for crystallization of compound (1) by mixing a solution of the compound (1) in a water-miscible good solvent with water, in which a slurry with a necessary suspension amount of the compound (1) for inhibiting oil formation and scaling is prepared in advance and then a main crystallization is carried out in the presence of said slurry.

Abstract translation: 本发明旨在以高产率制备由下式（1）表示的羟基羧酸的高纯度晶体。 提供化合物（1）的结晶方法，其包括酸化化合物（1）的碱金属盐和有机溶剂的溶液的混合物，以及通过将化合物（1）的溶液 将与化合物（1）在水混溶性好的溶剂中与水一起预先制备具有用于抑制油形成和结垢的化合物（1）所需悬浮液量的浆料，然后进行主结晶 所述浆料的存在。

公开(公告)号：US07034180B2

公开(公告)日：2006-04-25

申请号：US10362460

申请日：2001-09-07

Applicant: Masafumi Fukae ,  Yoshiro Hiraishi

Inventor： Masafumi Fukae ,  Yoshiro Hiraishi

IPC: C07C61/12

CPC classification number: C07C51/02 ,  C07C51/43 ,  C07C2602/28 ,  C07C59/46

Abstract: The invention aims at producing high-purity crystals of a hydroxycarboxylic acid represented by the following formula (1): in high yield. Provided are a method for crystallization of a compound (1) which comprises acidifying a mixture of a solution of an alkali salt of the compound (1) and an organic solvent, and a method for crystallization of compound (1) by mixing a solution of the compound (1) in a water-miscible good solvent with water, in which a slurry with a necessary suspension amount of the compound (1) for inhibiting oil formation and scaling is prepared in advance and then a main crystallization is carried out in the presence of said slurry.

Abstract translation: 本发明旨在以高产率制备由下式（1）表示的羟基羧酸的高纯度晶体。 提供化合物（1）的结晶方法，其包括酸化化合物（1）的碱金属盐和有机溶剂的溶液的混合物，以及通过将化合物（1）的溶液 将与化合物（1）在水混溶性好的溶剂中与水一起预先制备具有用于抑制油形成和结垢的化合物（1）所需悬浮液量的浆料，然后进行主结晶 所述浆料的存在。

公开(公告)号：US06784310B2

公开(公告)日：2004-08-31

申请号：US10019318

申请日：2002-04-24

Applicant: Masafumi Fukae

Inventor： Masafumi Fukae

IPC: C07C20500

CPC classification number: C07D263/44

Abstract: A crystallization is carried out by adding a solution of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxylic anhydride in a good solvent to an aliphatic hydrocarbon solvent while inhibiting the oil formation and scaling of said N-carboxylic anhydride. Further, a crystallization is carried out by adding an aliphatic hydrocarbon solvent sequentially to a solution of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxylic anhydride in a good solvent over not less than ¼ of an hour and at a temperature of not higher than 60° C.

Abstract translation: 通过在良溶剂中将N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酸N-羧酸酐的溶液加入到脂族烃溶剂中同时抑制所述的 此外，通过在良溶剂中向N-（1（S） - 乙氧基羰基-3-苯基丙基）-L-丙氨酸N-羧酸酐的溶液中依次加入脂族烃溶剂来进行结晶， 不小于1/4小时，温度不高于60℃。