公开(公告)号：KR1020060010000A

公开(公告)日：2006-02-02

申请号：KR1020040058550

申请日：2004-07-27

Applicant: 한국화학연구원 ,  화일약품주식회사

Inventor： 박태호 ,  이상호 ,  우혜경 ,  양민승

IPC: C07D207/273 ,  A61P25/28

Abstract: 본 발명은 뇌기능 개선작용 및 치매 치료 효과를 나타내는 1-카바모일메틸-4-하이드록시-2-피롤리디논(옥시라세탐)의 광학 (S)-이성체 또는 (R)-이성체를 용이하게 제조하는 방법에 관한 것으로, 본 발명에 따라 1-(S 또는 R)-페닐에틸-4-(S 또는 R)-히드록시-2-피롤리디논을 유기용매 존재 하에 아세틸화시키고, 생성된 1-(S 또는 R)-페닐에틸-4-(S 또는 R)-아세톡시-2-피롤리디논을 유기용매 존재 하에 탈벤질화 시킨 후, 생성된 4-(S 또는 R)-알콕시-2-피롤리디논을 유기용매 및 염기 존재 하에 할로겐으로 치환된 아세테이트와 반응시킨 다음, 생성된 1-에톡시카보닐메틸-4-(S 또는 R)-2-피롤리디논을 암모니아와 반응시키는 단계를 포함하는 1-카바모일-4-(S 또는 R)-히드록시-2-피롤리디논의 제조방법은 저가의 원료물질들을 사용하여 산업적 적용이 용이한 공정으로 (S)-옥시라세탐 또는 (R)-옥시라세탐을 고수율 및 고순도로 제조할 수 있으므로 뇌기능 개선 및 치매 치료제 개발에 유용하게 활용될 수 있다.

公开(公告)号：KR100449750B1

公开(公告)日：2004-09-22

申请号：KR1020010078759

申请日：2001-12-13

Applicant: 화일약품주식회사

Inventor： 양민승 ,  우혜경 ,  이영남

IPC: C07C67/30

Abstract: PURPOSE: A process for preparing racemic alkyl 4-chloro-3-hydroxybutyrate is provided to save the manufacturing costs required to produce the desired compound by using inexpensive starting materials under simple reaction conditions. CONSTITUTION: The process for preparing racemic alkyl 4-chloro-3-hydroxybutyrate which is useful as an essential intermediate for oxiracetam utilizes inexpensive alkyl 4-chloroacetoacetate as a starting material. The process is characterized by comprising reducing alkyl 4-chloroacetoacetate represented by the formula(1) in the presence of sodium borohydride and an acid catalyst in an organic solvent to obtain alkyl 4-chloro-3-hydroxybutyrate represented by the formula(2), wherein R is a C1-C4 lower alkyl.

Abstract translation: 目的：提供一种制备4-氯-3-羟基丁酸外消旋烷基酯的方法，通过在简单的反应条件下使用便宜的原料来节省生产所需化合物所需的制造成本。 构成：制备可用作奥拉西坦必需中间体的4-氯-3-羟基丁酸外消旋烷基酯的方法利用廉价的4-氯乙酰乙酸烷基酯作为原料。 该方法的特征在于包括在硼氢化钠和酸催化剂存在下，在有机溶剂中还原由式（1）表示的4-氯乙酰乙酸烷基酯以获得由式（2）表示的4-氯-3-羟基丁酸烷基酯， 其中R是C 1 -C 4低级烷基。

公开(公告)号：KR1020030082525A

公开(公告)日：2003-10-22

申请号：KR1020030069901

申请日：2003-10-08

Applicant: 화일약품주식회사

Inventor： 박태호 ,  양민승 ,  왕한철 ,  우혜경 ,  김종호 ,  윤진영

IPC: C07D207/14

Abstract: PURPOSE: An intermediate for preparing levosulpiride and a preparation method thereof are provided, thereby preparing levosulpiride in higher yield and purity. CONSTITUTION: An intermediate represented by the formula (V) for preparing levosulpiride of the formula (I) is provided, wherein R1 and R2 are independently hydrogen, C1-C4 lower alkyl or phenyl; R3 is phenyl derivative of the formula (VIII) or naphthyl derivative of the formula (IX); and X is hydrogen or halogen, provided that the formula (V) may be racemic body, (S) body and (R) body because it contains chiral carbon(*). A method for preparing an intermediate of the formula (V) for preparing levosulpiride comprises activating a compound of the formula (IV) in the presence of base using acid anhydride method, acid chloride method or azide method, and reacting the activated compound of the formula (IV) with 2-methoxy-5-sulfamoyl benzoic acid, wherein R1 and R2 are independently hydrogen, C1-C4 lower alkyl or phenyl; R3 is phenyl derivative of the formula (VIII) or naphthyl derivative of formula (IX); and X is hydrogen or halogen.

Abstract translation: 目的：提供一种制备左美沙比妥的中间体及其制备方法，从而以更高的产率和纯度制备左美沙非尼。 构成：提供由式（I）表示的式（Ⅴ）表示的中间体，其中R 1和R 2独立地为氢，C 1 -C 4低级烷基或苯基; R3是式（VIII）的苯基衍生物或式（IX）的萘基衍生物; 并且X是氢或卤素，条件是式（V）可以是外消旋体，（S）体和（R）体，因为它含有手性碳（*）。 制备式（Ⅴ）中间体的制备方法，包括使用酸酐法，酰氯法或叠氮化物法在碱的存在下活化式（Ⅳ）的化合物，并使式 （IV）与2-甲氧基-5-氨磺酰基苯甲酸，其中R 1和R 2独立地是氢，C 1 -C 4低级烷基或苯基; R3是式（VIII）的苯基衍生物或式（IX）的萘基衍生物; X为氢或卤素。

公开(公告)号：KR1020030048748A

公开(公告)日：2003-06-25

申请号：KR1020010078759

申请日：2001-12-13

Applicant: 화일약품주식회사

Inventor： 양민승 ,  우혜경 ,  이영남

IPC: C07C67/30

Abstract: PURPOSE: A process for preparing racemic alkyl 4-chloro-3-hydroxybutyrate is provided to save the manufacturing costs required to produce the desired compound by using inexpensive starting materials under simple reaction conditions. CONSTITUTION: The process for preparing racemic alkyl 4-chloro-3-hydroxybutyrate which is useful as an essential intermediate for oxiracetam utilizes inexpensive alkyl 4-chloroacetoacetate as a starting material. The process is characterized by comprising reducing alkyl 4-chloroacetoacetate represented by the formula(1) in the presence of sodium borohydride and an acid catalyst in an organic solvent to obtain alkyl 4-chloro-3-hydroxybutyrate represented by the formula(2), wherein R is a C1-C4 lower alkyl.

Abstract translation: 目的：提供制备外消旋4-氯-3-羟基丁酸烷基酯的方法，以在简单的反应条件下通过使用廉价的起始原料来节省生产所需化合物所需的制造成本。 构成：用作奥拉西坦的必需中间体的4-氯-3-羟基丁酸外消旋烷基酯的方法利用廉价的4-氯乙酰乙酸烷基酯作为原料。 该方法的特征在于在硼氢化钠和酸催化剂存在下，在有机溶剂中还原由式（1）表示的4-氯乙酰乙酸烷基酯，得到由式（2）表示的4-氯-3-羟基丁酸烷基酯， 其中R是C1-C4低级烷基。

公开(公告)号：KR1020020092123A

公开(公告)日：2002-12-11

申请号：KR1020010031027

申请日：2001-06-02

Applicant: 화일약품주식회사

Inventor： 박태호 ,  양민승 ,  왕한철 ,  우혜경 ,  김종호 ,  윤진영

IPC: C07D207/14

Abstract: PURPOSE: Provided are a method for preparing Levosulpiride which increases the pressure of a sphincteral muscle, promotes the vermiculation of the gullet and facilitates digestion, in high yield and purity and intermediates used therein. CONSTITUTION: The method for preparing Levosulpiride of the formula(I) is characterized by treating a compound of the formula(V) with trifluoroacetate. In the formulae, R1 and R2 are independently hydrogen atom or 1-4 of lower alkyl or phenyl; R3 is a phenyl derivative of the formula(VIII) or naphthyl derivative of the formula(IX).

Abstract translation: 目的：提供一种制备左旋舒巴替罗的方法，其增加括约肌的压力，促进食道的呕吐并促进以高产率和纯度消化，以及其中使用的中间体。 构成：式（I）的左旋苏布里德的制备方法的特征在于用三氟乙酸盐处理式（V）的化合物。 在该式中，R 1和R 2独立地为氢原子或1-4个低级烷基或苯基; R3是式（VIII）的苯基衍生物或式（IX）的萘基衍生物。

公开(公告)号：KR1020000060138A

公开(公告)日：2000-10-16

申请号：KR1019990008224

申请日：1999-03-12

Applicant: 화일약품주식회사

Inventor： 우남태 ,  양민승 ,  우혜경 ,  김종호

IPC: C07C229/30

Abstract: PURPOSE: A new preparation of 4-amino-5-hexenoic acid is provided that produces economically 4-amino-5-hexenoic acid through simple processes using glutamic acid-5-benzylester as a starting material. CONSTITUTION: The preparation of 4-amino-5-hexenoic acid (vinyl γ-aminobutyric acid) comprises the step of preparing the desired compound via new intermediates of Formula (II), (III) and (IV) from glutamic acid-5-benzylester of Formula (I) derived from glutamic acid. More particularly, the preparation of 4-amino-5-hexenoic acid of Formula (A) comprises hydrolyzing 4-£(benzyloxy)carbonyl|amino-5-hexenoic acid benzyl ester £Formula (IV)| in the presence of Pd/C catalyst. The preparation of the desired compound (I) comprises the step of subjecting benzyl-4-{£(benzyloxy)carbonyl|amino}-5-oxopentanoate £Formula (III)| to a Wittig reaction. Also, the preparation of benzyl-4-{£(benzyloxy)carbonyl|amino}-5-oxopentanoate £Formula (III)| comprises the steps of reacting glutamic acid-5-benzylester £Formula (I)| with benzyl chloroformate to provide N-benzyloxycarbonyl glutamic acid-5-benzylester £Formula (II)|, and then directly reducing the compound of Formula (II) or converting the carboxyl group of the compound represented by Formula (II) to an alcohol group using NaBH4 and ethylchloroformate followed by subjecting to a Swern Oxidation.

Abstract translation: 目的：提供4-氨基-5-己烯酸的新制剂，其通过使用谷氨酸-5-苄基酯作为起始原料的简单方法生产经济地4-氨基-5-己烯酸。 构成：4-氨基-5-己烯酸（乙烯基γ-氨基丁酸）的制备包括通过式（II），（III）和（IV）的新中间体从谷氨酸-5- 式（I）的苄基酯衍生自谷氨酸。 更具体地，式（A）的4-氨基-5-己烯酸的制备包括水解4-（苄氧基）羰基|氨基-5-己烯酸苄酯，式（IV） 在Pd / C催化剂存在下。 所需化合物（I）的制备包括使苄基-4- {（（苄氧基）羰基}氨基} -5-氧代戊酸酯（III） 维特希反应。 另外，制备苄基-4- {（（苄氧基）羰基）氨基} -5-氧代戊酸酯。 包括使谷氨酸-5-苄酯与式（I）反应的步骤 用氯甲酸苄酯提供N-苄氧羰基谷氨酸-5-苄酯，式（II）|，然后直接还原式（II）化合物或将式（II）表示的化合物的羧基转化为醇基 使用NaBH 4和氯甲酸乙酯，然后进行Swern氧化。