公开(公告)号：EP1035131A4

公开(公告)日：2002-05-02

申请号：EP99944783

申请日：1999-09-22

Applicant: KANEKA CORP

Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02 ,  C07K5/06

CPC classification number: C07K5/0222

Abstract: A process for preparing N -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline (2) easily, efficiently and industrially advantageously, which comprises: the first step of conducting the alkaline hydrolysis of an N -(1(S)-alkoxycarbonyl-3-phenylpropyl)-N -trifluoroacetyl-L-lysyl-L-proline (1) by the use of n molar equivalents (wherein n >/= 3) of an inorganic base per mol of the compound (1) either in a mixture of water with a hydrophilic organic solvent or in water; the second step of neutralizing the resulting reaction mixture with (n-1) to n molar equivalents (wherein n >/= 3) of an inorganic acid, replacing the solvent system by a suitable one to thereby precipitate an inorganic salt formed by the above neutralization, and separating and removing the salt; and the third step of crystallizing the compound (2) present in the liquid mixture left after the above removal of the salt at its isoelectric point and recovering the compound (2) as a crystal, while salts mainly comprising organic acid salts resulting from trifluoroacetic acid remain dissolved in the mother liquor.

公开(公告)号：EP0967221A4

公开(公告)日：2002-05-02

申请号：EP98932585

申请日：1998-07-21

Applicant: KANEKA CORP

Inventor： UEDA YASUYOSHI ,  KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE

IPC: A61P9/12 ,  C07K1/02 ,  C07K1/08 ,  C07K5/02 ,  C07K5/06 ,  C07K5/062

CPC classification number: C07K5/0222 ,  C07K5/06026

Abstract: A process for preparing pharmacologically acceptable salts of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acids, comprising the steps of: condensing an amino acid with N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxyanhydride under basic conditions; decarboxylating the condensate under neutral to acidic conditions to prepare an N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acid; and converting the product to a pharmacologically acceptable salt thereof, characterized in that a series of procedures up to the formation of a pharmacologically acceptable salt or up to the withdrawal of the pharmaceutically acceptable salt thereof are carried out in an aqueous liquid to inhibit the production of a by-product (3). According to this process, high-quality pharmacologically acceptable salts of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acids can be prepared in high yields in a cost-effective manner on a commercial scale.

Abstract translation: 制备N-（1（S） - 乙氧羰基-3-苯丙基）-L-丙氨酰氨基酸的药理学上可接受的盐的方法，包括以下步骤：使氨基酸与N-（1（S） - 乙氧羰基-3 - 苯基丙基）-L-丙氨酸N-羧酸酐在碱性条件下; 在中性至酸性条件下将缩合物脱羧基以制备N-（1（S） - 乙氧羰基-3-苯丙基）-L-丙氨酰氨基酸; 并将该产物转化成其药理学上可接受的盐，其特征在于在含水液体中进行一系列形成药理学上可接受的盐或直至其药学上可接受的盐的程序，以抑制 一个副产品（3）。 根据该方法，可以以商业规模以高成本效益的方式高产率地制备N-（1（S） - 乙氧羰基-3-苯丙基）-L-丙氨酰氨基酸的高质量药理学上可接受的盐。

公开(公告)号：JP2010100651A

公开(公告)日：2010-05-06

申请号：JP2010015834

申请日：2010-01-27

Applicant: Kaneka Corp ,  株式会社カネカ

Inventor： KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIBUMI ,  NAGASHIMA NOBUO ,  SAKA YASUHIRO ,  HONDA TATSUYA ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07D307/20

Abstract: PROBLEM TO BE SOLVED: To provide high-purity 3-hydroxytetrahydrofuran in a high yield easily and simply by an industrially advantageous process.
SOLUTION: The process includes: reducing a 4-halo-3-hydroxybutyric acid ester with a boron hydride compound and/or an aluminum hydride compound in an organic solvent immiscible with water; treating the reaction mixture with an acid and water to convert it into the corresponding 4-halo-1, 3-butanediol and at the same time obtaining an aqueous solution containing the compound; carrying out the cyclization reaction in the aqueous solution; extracting the resulting 3-hydroxytetrahydrofuran from the aqueous solution using an organic solvent immiscible with water; and isolating the 3-hydroxytetrahydrofuran by concentration and/or distillation of the solution obtained.
COPYRIGHT: (C)2010,JPO&INPIT

Abstract translation: 待解决的问题：通过工业上有利的方法容易且简单地提供高产率的高纯度3-羟基四氢呋喃。 解决方案：该方法包括：用氢化硼化合物和/或氢化铝化合物在与水不混溶的有机溶剂中还原4-卤-3-羟基丁酸酯; 用酸和水处理反应混合物，将其转化成相应的4-卤代-1,3-丁二醇，同时得到含有该化合物的水溶液; 在水溶液中进行环化反应; 使用与水不混溶的有机溶剂从水溶液中萃取所得3-羟基四氢呋喃; 并通过所得溶液的浓缩和/或蒸馏分离3-羟基四氢呋喃。 版权所有（C）2010，JPO＆INPIT