KR100461561B1 - (S) -3-carboxy-4-bromobutyric acid production method - Google Patents
(S) -3-carboxy-4-bromobutyric acid production method Download PDFInfo
- Publication number
- KR100461561B1 KR100461561B1 KR10-1998-0029909A KR19980029909A KR100461561B1 KR 100461561 B1 KR100461561 B1 KR 100461561B1 KR 19980029909 A KR19980029909 A KR 19980029909A KR 100461561 B1 KR100461561 B1 KR 100461561B1
- Authority
- KR
- South Korea
- Prior art keywords
- acid
- carboxy
- reaction
- bromobutyric
- hydroxybutyrolactone
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/24—Preparation of carboxylic acid esters by reacting carboxylic acids or derivatives thereof with a carbon-to-oxygen ether bond, e.g. acetal, tetrahydrofuran
- C07C67/26—Preparation of carboxylic acid esters by reacting carboxylic acids or derivatives thereof with a carbon-to-oxygen ether bond, e.g. acetal, tetrahydrofuran with an oxirane ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
Abstract
본 발명은 (S)-3-카르복시-4-브로모부티르산의 제조방법에 관한 것으로서, 더욱 상세하게는 광학활성을 가지는 (S)-3-히드록시부티로락톤을 브롬화 시약과 카르복시산 존재하에서 반응시켜 높은 수율 및 높은 광학순도로 다음 화학식 1로 표시되는 (S)-3-카르복시-4-브로모부티르산을 제조하는 방법에 관한 것이다.The present invention relates to a method for preparing (S) -3-carboxy-4-bromobutyric acid, and more particularly, to reaction of (S) -3-hydroxybutyrolactone having optical activity in the presence of a bromination reagent and carboxylic acid. It relates to a method for producing (S) -3-carboxy-4-bromobutyric acid represented by the following formula (1) in high yield and high optical purity.
상기 화학식 1에서 : R은 수소원자 또는 탄소원자수 1 ∼ 4의 알킬기를 나타낸다.In Formula 1, R represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
Description
본 발명은 (S)-3-카르복시-4-브로모부티르산의 제조방법에 관한 것으로서, 더욱 상세하게는 광학활성을 가지는 (S)-3-히드록시부티로락톤을 브롬화 시약과 카르복시산 존재하에서 반응시켜 높은 수율 및 높은 광학순도로 다음 화학식 1로 표시되는 (S)-3-카르복시-4-브로모부티르산을 제조하는 방법에 관한 것이다.The present invention relates to a method for preparing (S) -3-carboxy-4-bromobutyric acid, and more particularly, to reaction of (S) -3-hydroxybutyrolactone having optical activity in the presence of a bromination reagent and carboxylic acid. It relates to a method for producing (S) -3-carboxy-4-bromobutyric acid represented by the following formula (1) in high yield and high optical purity.
화학식 1Formula 1
상기 화학식 1에서 : R은 수소원자 또는 탄소원자수 1 ∼ 4의 알킬기를 나타낸다.In Formula 1, R represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
상기 화학식 1로 표시되는 광학활성을 갖는 (S)-3-카르복시-4-브로모부티르산은 항생제, 고혈압치료제, 고지혈증 치료제 및 정신성약물 제조에 유용한 중요 중간물질이다. 이에, 상기 화학식 1로 표시되는 (S)-3-카르복시-4-브로모부티르산을 유용한 키랄중간체로 사용하기 위한 연구가 활발히 진행되어 왔다.(S) -3-carboxy-4-bromobutyric acid having optical activity represented by Chemical Formula 1 is an important intermediate useful for preparing antibiotics, hypertension, hyperlipidemia, and psychotropic drugs. Accordingly, studies have been actively conducted to use (S) -3-carboxy-4-bromobutyric acid represented by Chemical Formula 1 as a useful chiral intermediate.
상기 화학식 1로 표시되는 (S)-3-카르복시-4-브로모부티르산과 비교되는 유사 구조를 가지는 다른 화합물의 제조방법을 살펴보면 다음과 같다. Looking at the manufacturing method of another compound having a similar structure compared to (S) -3-carboxy-4-bromobutyric acid represented by the formula (1) as follows.
미합중국특허 제5,413,921호 및 미합중국특허 제5,559,030호에서는 3-옥소-4-클로로부티르산 에스테르를 효소를 이용한 환원반응에 의해 3-히드록시-클로로부티르산 에스테르를 합성하는 방법이 개시되어 있다. 이러한 생화학적인 합성방법은 특성상 반응기간이 장기화되고 목적물의 분리 및 정제과정이 매우 복잡한 문제가 있다.US Pat. No. 5,413,921 and US Pat. No. 5,559,030 disclose methods for synthesizing 3-hydroxy-chlorobutyric acid esters by reduction of 3-oxo-4-chlorobutyric acid esters with enzymes. Such biochemical synthesis has a problem in that the reaction period is prolonged and the process of separation and purification of the target is very complicated.
미합중국특허 제5,087,751호에는 (R)-3-클로로-1,2-프로판디올의 시안화 반응에 의해 (S)-3,4-디히드록시부티로니트릴을 합성하고, 이를 가수분해하여 (S)-3,4-디히드록시부티르산을 제조하는 방법이 공지되어 있지만, 이 방법은 다단계 반응 및 공업적으로 다루기 어려운 시아노 화합물을 사용하는 결점이 있다.U.S. Patent No. 5,087,751 discloses (S) -3,4-dihydroxybutyronitrile by the cyanation reaction of (R) -3-chloro-1,2-propanediol, and hydrolyzes it to (S) Although methods for preparing -3,4-dihydroxybutyric acid are known, this method has the drawback of using a multistage reaction and cyano compounds which are difficult to handle industrially.
Tetrahedron 46, 4277(1990)에 의하면 (S)-3-히드록시부티로락톤에 트리메틸실릴 요오드 및 에탄올을 사용하여 (S)-3-히드록시-4-요오드부티르산 에틸 에스테르를 제조하는 방법이 공지되어 있으나, 무수의 반응조건 및 고가의 트리메틸실릴 요오드를 사용해야 하는 단점이 있다.Tetrahedron 46, 4277 (1990) discloses a process for preparing (S) -3-hydroxy-4-iodobutyric acid ethyl ester using trimethylsilyl iodine and ethanol in (S) -3-hydroxybutyrolactone. However, there are disadvantages of using anhydrous reaction conditions and expensive trimethylsilyl iodine.
또한, 일본국 공개특허 평4-149,151호에서는 (S)-3-히드록시부티로락톤에 브롬산/유기산 및 알콜을 사용하여 (S)-3-히드록시-4-브로모부티르산 에스테르를 제조하고 있다. 다음 반응식 1에 나타낸 바와 같은 일본국 공개특허 평4-149,151호와 본 발명을 비교하면, 카르복시산 및 알콜을 대신하여 본 발명이 반응시약겸 용매로서 카르복시산을 단독으로 사용하는데 그 차이가 있며, 이로 인하여 반응 메카니즘은 크게 달라지고, 수득물질 역시 전혀 상이하다. In addition, Japanese Patent Application Laid-open No. Hei 4-149,151 prepares (S) -3-hydroxy-4-bromobutyric acid ester by using bromic acid / organic acid and alcohol in (S) -3-hydroxybutyrolactone. Doing. Comparing the present invention with Japanese Unexamined Patent Publication No. 4-149,151 as shown in Scheme 1, there is a difference in that the present invention uses carboxylic acid alone as a reaction reagent and a solvent in place of carboxylic acid and alcohol. The reaction mechanism varies greatly and the materials obtained are also completely different.
상기 수득물질에 있어서도, (S)-3-히드록시-4-브로모부티르산 에스테르는 의 경우, 일반적으로 유기용매에 난용인 친핵반응물과의 반응 용이하지 아니하여 반응시간(약 24시간)이 길고 수율도 매우 저조하며, 또한 수용액에서 반응성이 좋은 (S)-3,4-에폭시부티르산 염을 제조하기 위해서는 에스테르기를 가수분해한 후 염기로 처리하여 (S)-3,4-에폭시부티르산 염을 제조해야 하는 번거러움이 존재한다. 이에 반하여 (S)-3-카르복시-4-브로모부티르산은 수용액상에서의 반응성이 우수하여 친핵반응이 용이하고 짧은 반응시간(약 3시간)내에 고수율로 반응을 수행할 수 있는 장점이 있으며, 또한 (S)-3,4-에폭시부티르산 염의 제조시에 3-히드록시기에 보호기를 도입해야 하는 추가 공정이 필요없는 등 산업적으로 매우 유용한 중간체 화합물이다.Also in the obtained material, in the case of (S) -3-hydroxy-4-bromobutyric acid ester, reaction time with the nucleophilic reactants, which are generally poorly soluble in an organic solvent, is not easy to react, and thus the reaction time is about 24 hours. In order to prepare a long, very low yield and highly reactive (S) -3,4-epoxybutyric acid salt in an aqueous solution, the ester group is hydrolyzed and treated with a base to obtain (S) -3,4-epoxybutyric acid salt. There is a hassle to manufacture. On the contrary, (S) -3-carboxy-4-bromobutyric acid has an advantage in that it is excellent in reactivity in aqueous solution, so that the nucleophilic reaction is easy and the reaction can be performed in high yield within a short reaction time (about 3 hours). It is also an industrially useful intermediate compound, such as the need for introducing a protecting group into the 3-hydroxy group in the preparation of the (S) -3,4-epoxybutyric acid salt.
이에 본 발명의 발명자들은 산업적인 이용 가치가 우수한 (S)-3-카르복시-4-브로모부티르산을 보다 경제적이고 효율적으로 제조하는 방법을 찾기 위해 노력하였고, 그 결과 (S)-3-히드록시부티로락톤을 원료물질로 하고 브롬화시약과 함께 반응용매겸 반응시약으로서 카르복시산을 사용하여 (S)-3-카르복시-4-브로모부티르산을 높은 수율로 얻을 수 있는 새로운 제법을 개발하므로써 본 발명을 완성하였다.Therefore, the inventors of the present invention have tried to find a more economical and efficient method for producing (S) -3-carboxy-4-bromobutyric acid having excellent industrial value, and as a result, (S) -3-hydroxy The present invention is developed by developing a novel method for obtaining (S) -3-carboxy-4-bromobutyric acid in high yield using butyrolactone as a raw material and carboxylic acid as a reaction solvent and reaction reagent together with a bromination reagent. Completed.
또한, 본 발명에서 기술하고 있는 제조방법은 광학활성을 갖는 (S)-3-히드록시부티로락톤을 사용하여 (S)-입체이성질체로 변화시키는 기술로 아직 시도된 바 없으며, 그 신규성이나 응용성 및 용이성이 매우 선도적이라 할 수 있다.In addition, the production method described in the present invention has not yet been attempted as a technique for converting into (S) -stereoisomers using (S) -3-hydroxybutyrolactone having optical activity, and its novelty and application It is very leading in ease and ease.
(S)-3-히드록시부티로락톤을 출발물질로하여 (S)-3-카르복시-4-브로모부티르산을 제조하는 방법에 있어서, In the method for producing (S) -3-carboxy-4-bromobutyric acid using (S) -3-hydroxybutyrolactone as a starting material,
(S)-3-히드록시부티로락톤에 브롬화시약 및 RCOOH(이때, R은 탄소원자수 1 ∼ 7의 알킬기임)로 표시되는 카르복시산을 사용하여, 0 ∼ 100℃ 반응온도 범위내에서 반응시켜 제조하는 다음 화학식 1로 표시되는 (S)-3-카르복시-4-브로모부티르산의 제조방법을 그 특징으로 한다.Prepared by reacting (S) -3-hydroxybutyrolactone with a bromination reagent and a carboxylic acid represented by RCOOH (wherein R is an alkyl group having 1 to 7 carbon atoms) within a reaction temperature range of 0 to 100 ° C. It is characterized by a method for producing (S) -3-carboxy-4-bromobutyric acid represented by the following formula (1).
화학식 1Formula 1
상기 화학식 1에서 : R은 수소원자 또는 탄소원자수 1 ∼ 4의 알킬기를 나타낸다.In Formula 1, R represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
이와 같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.
본 발명에서 원료물질로 이용하는 (S)-3-히드록시부티로락톤은 유럽특허 제513,430호에 예시된 방법에 의해 젖당으로부터 경제적으로 합성하여 사용한다.(S) -3-hydroxybutyrolactone used as a raw material in the present invention is economically synthesized from lactose by the method exemplified in European Patent No. 513,430.
또한, 본 발명에서는 1.0 ∼ 5.0 당량 만큼의 브롬화 시약이 포함된 카르복시산 존재하에서 1 당량의 (S)-3-히드록시부티로락톤을 0 ∼ 100℃의 온도로 1 ∼ 20시간 반응시키면 (S)-3-카르복시-4-브로모부티르산으로 변환된다. 그리고, 수득된 유기산을 염화메탄으로 희석한 후 아세트산나트륨 수용액으로 세척후 건조한다. In the present invention, when 1 equivalent of (S) -3-hydroxybutyrolactone is reacted at a temperature of 0 to 100 ° C for 1 to 20 hours in the presence of carboxylic acid containing as much as 1.0 to 5.0 equivalents of bromination reagent (S) Is converted to 3-carboxy-4-bromobutyric acid. The organic acid obtained is diluted with methane chloride, washed with an aqueous sodium acetate solution and dried.
본 발명의 브롬화 반응에 적용되는 시약은 브롬산, 브로모나트륨과 황산, 브로모나트륨과 염산 및 브로모나트륨과 인산 중에서 선택하여 사용하며, 특히 바람직하기로는 브롬산을 사용하는 것이다. The reagent applied to the bromination reaction of the present invention is selected from bromic acid, bromo sodium and sulfuric acid, bromo sodium and hydrochloric acid, bromo sodium and phosphoric acid, and particularly preferably bromic acid.
특히, 본 발명에서는 특징적으로 반응용매겸 반응시약으로서 카르복시산을 사용한다. 카르복시산으로는 포름산은 물론이고 아세트산을 비롯한 탄소원자수 1 ∼ 4의 알킬카르복시산을 포함하며, 이는 각각 단독으로 사용하거나 또는 2종 이상을 혼합 사용할 수 있다. In particular, the present invention uses carboxylic acid as a reaction solvent and reaction reagent. Carboxylic acid includes not only formic acid but also alkylcarboxylic acid having 1 to 4 carbon atoms including acetic acid, which may be used alone or in combination of two or more thereof.
본 발명이 특징적으로 사용하고 있는 카르복시산은 반응 용매로서의 역할은 물론이고 알콜을 용매로 사용하는 방법에서의 고리열림반응이 느리게 진행되는 단점을 개선하고, 역반응 진행을 억제하여 목적물에 대한 수율도 높히면서 3-히드록시기의 보호기를 도입하는 별도의 공정없이도 사용된 카르복시산 용매로 보호된 형태의 (S)-3-카르복시-4-브로모부티르산이 직접 얻어진다. Carboxylic acid, which is characteristically used in the present invention, improves the disadvantage of slow reaction of ring opening in the method of using alcohol as a solvent as well as a reaction solvent, and suppresses the progress of reverse reaction, thereby increasing the yield for the target product. Directly obtained (S) -3-carboxy-4-bromobutyric acid in the form protected with the carboxylic acid solvent used without the separate process of introducing a protecting group of a 3-hydroxy group.
상기한 바와 같은 본 발명에 따른 제조방법으로 얻어진 (S)-3-카르복시-4-브로모부티르산의 수율은 90% 이상이다.The yield of (S) -3-carboxy-4-bromobutyric acid obtained by the production method according to the present invention as described above is 90% or more.
이하, 본 발명을 다음의 실시예에 의거하여 더욱 상세히 설명하겠는 바, 본 발명이 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail based on the following examples, but the present invention is not limited by the examples.
실시예 1 : (S)-3-아세톡시-4-브로모부티르산의 제조 Example 1 Preparation of (S) -3-acetoxy-4-bromobutyric acid
온도계, 환류냉각기, 교반기가 부착된 500 ㎖ 3구 플라스크에 85% (S)-3-히드록시부티로락톤(10 g)과 30% 브롬산/아세트산 용액(40 ㎖)을 넣고 40 ∼ 80℃에서 3시간동안 교반하였다. 반응 완결후 상온으로 냉각하고 염화메탄(200 ㎖)을 첨가하고 아세트산나트륨 수용액으로 세척한 후 건조하였다. 유기층을 분리하여 무수 황산마그네슘을 첨가하여 수분을 제거하고 여과한 후 농축하였으며, 그 결과 (S)-3-아세톡시-4-브로모부티르산 17.2 g(수율 92%)을 얻었다. In a 500 ml three-necked flask equipped with a thermometer, a reflux condenser and a stirrer, add 85% (S) -3-hydroxybutyrolactone (10 g) and 30% bromic acid / acetic acid solution (40 ml) to 40 to 80 ° C. Stirred for 3 h. After completion of the reaction, the reaction mixture was cooled to room temperature, methane chloride (200 mL) was added, washed with aqueous sodium acetate solution, and dried. The organic layer was separated, anhydrous magnesium sulfate was added to remove water, filtered and concentrated. As a result, 17.2 g (yield 92%) of (S) -3-acetoxy-4-bromobutyric acid was obtained.
1H-NMR(CDCl3, ppm) : δ2.1(s, 3H, CH3COO), 2.8∼2.9(dd, 2H, CH2COOH), 3.5∼ 3.6(dd, 2H, BrCH2CH), 5.3∼5.4(m,1H, BrCH2CH). 1 H-NMR (CDCl 3 , ppm): δ 2.1 (s, 3H, CH 3 COO), 2.8 to 2.9 (dd, 2H, CH 2 COOH), 3.5 to 3.6 (dd, 2H, BrCH 2 CH), 5.3 to 5.4 (m, 1H, BrCH 2 CH).
실시예 2 : (S)-3-푸로판노일-4-브로모부티르산의 제조 Example 2 Preparation of (S) -3-Furopannoyl-4-bromobutyric acid
온도계, 환류냉각기, 교반기가 부착된 500 ㎖ 3구 플라스크에 85% (S)-3-히드록시부티로락톤(10 g)과 30% 브롬산/푸로판산 용액(40 ㎖)을 넣고 40 ∼ 80℃에서 5시간동안 교반하였다. 반응 완결후 상온으로 냉각하고 염화메탄(200 ㎖)을 첨가하고 아세트산나트륨 수용액으로 세척한 후 건조하였다. 유기층을 분리하여 무수 황산마그네슘을 첨가하여 수분을 제거하고 여과한 후 농축하였으며, 그 결과 (S)-3-푸로판노일-4-브로모부티르산 18.1 g(수율 91%)을 얻었다. In a 500 ml three-necked flask equipped with a thermometer, reflux condenser and stirrer, add 85% (S) -3-hydroxybutyrolactone (10 g) and 30% bromic acid / furopanic acid solution (40 ml). Stir at 5 ° C. for 5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, methane chloride (200 mL) was added, washed with aqueous sodium acetate solution, and dried. The organic layer was separated, anhydrous magnesium sulfate was added to remove water, filtered and concentrated. As a result, 18.1 g (91%) of (S) -3-furopannoyl-4-bromobutyric acid was obtained.
1H-NMR(CDCl3, ppm) : δ1.1(t, 3H, CH3CH2COO), 2.2(q, 2H, CH2COO), 2.8∼2.9(dd, 2H, CH2COOH), 3.5∼3.6(dd, 2H, BrCH2CH), 5.3∼5.4(m,1H, BrCH2CH). 1 H-NMR (CDCl 3 , ppm): δ 1.1 (t, 3H, CH 3 CH 2 COO), 2.2 (q, 2H, CH 2 COO), 2.8-2.9 (dd, 2H, CH 2 COOH), 3.5 to 3.6 (dd, 2H, BrCH 2 CH), 5.3 to 5.4 (m, 1H, BrCH 2 CH).
비교예 : (S)-4-브로모-3-히드록시부티르산 메틸 에스테르의 제조방법 Comparative Example: Method for preparing (S) -4-bromo-3-hydroxybutyric acid methyl ester
(S)-3-히드록시부티로락톤(0.5 g)을 30% 브롬산/아세트산 용액(3.5 ㎖)에 희석하여 24시간 교반한 후, 메탄올(12.5 ㎖)을 첨가하여 24시간 더 교반하였다. 이 반응액을 감압증류하여 남겨진 오렌지색의 기름을 에틸 아세테이트와 증류수를 첨가한 후, 탄산나트륨 수용액으로 pH를 7로 조정하였다. 유기층을 분리후 황산마그네슘으로 건조후 감압 증류(79 ∼ 81℃/1 mmHg)하여 (S)-4-브로모-3-히드록시브티르산 메틸 에스테르 0.72 g(수율 75%)을 획득하였다(S) -3-hydroxybutyrolactone (0.5 g) was diluted in 30% bromic acid / acetic acid solution (3.5 mL) and stirred for 24 hours, and then methanol (12.5 mL) was added and stirred for further 24 hours. The reaction solution was distilled under reduced pressure, and the remaining orange oil was added with ethyl acetate and distilled water, and then the pH was adjusted to 7 with aqueous sodium carbonate solution. The organic layer was separated, dried over magnesium sulfate, and distilled under reduced pressure (79 to 81 ° C / 1 mmHg) to obtain 0.72 g (yield 75%) of (S) -4-bromo-3-hydroxybutyric acid methyl ester.
본 발명에 따른 제조방법은 젖당으로부터 경제적으로 합성할 수 있는 (S)-3-히드록시부티로락톤을 출발물질로 활용하여, 신규 키랄 유도체 합성에 있어서 매우 유용한 중간체인 (S)-3-카르복시-4-브로모부티르산을 짧은 반응 시간과 높은 수율로 얻을 수 있는 효과를 가진다.The production method according to the present invention utilizes (S) -3-hydroxybutyrolactone, which can be economically synthesized from lactose, as a starting material, and is a very useful intermediate for the synthesis of novel chiral derivatives. It has the effect that 4-bromobutyric acid can be obtained with short reaction time and high yield.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-1998-0029909A KR100461561B1 (en) | 1998-07-24 | 1998-07-24 | (S) -3-carboxy-4-bromobutyric acid production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-1998-0029909A KR100461561B1 (en) | 1998-07-24 | 1998-07-24 | (S) -3-carboxy-4-bromobutyric acid production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20000009464A KR20000009464A (en) | 2000-02-15 |
| KR100461561B1 true KR100461561B1 (en) | 2005-04-06 |
Family
ID=19545116
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR10-1998-0029909A KR100461561B1 (en) | 1998-07-24 | 1998-07-24 | (S) -3-carboxy-4-bromobutyric acid production method |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR100461561B1 (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61146191A (en) * | 1984-12-20 | 1986-07-03 | Kanegafuchi Chem Ind Co Ltd | Production of (s)-gamma-halo-beta-hydroxybutyric acid ester |
| JPH04149151A (en) * | 1990-10-09 | 1992-05-22 | Kanegafuchi Chem Ind Co Ltd | Production of 4-bromo-3-hydroxybutyric acid ester derivative |
| JPH04173767A (en) * | 1990-11-02 | 1992-06-22 | Kanegafuchi Chem Ind Co Ltd | Production of 5,6-dihydroxy-3-oxohexanoic acid ester derivative |
| JPH06172256A (en) * | 1992-12-03 | 1994-06-21 | Kanegafuchi Chem Ind Co Ltd | Production of 3-hydroxybutyric acid derivative |
| JPH06209782A (en) * | 1993-01-12 | 1994-08-02 | Daicel Chem Ind Ltd | Production of optically active 4-halo-3-hydroxybutyric acid ester |
| JPH08336393A (en) * | 1995-04-13 | 1996-12-24 | Mitsubishi Chem Corp | Production of optically active gamma-substituted-beta-hydroxybutyric ester |
-
1998
- 1998-07-24 KR KR10-1998-0029909A patent/KR100461561B1/en not_active IP Right Cessation
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61146191A (en) * | 1984-12-20 | 1986-07-03 | Kanegafuchi Chem Ind Co Ltd | Production of (s)-gamma-halo-beta-hydroxybutyric acid ester |
| JPH04149151A (en) * | 1990-10-09 | 1992-05-22 | Kanegafuchi Chem Ind Co Ltd | Production of 4-bromo-3-hydroxybutyric acid ester derivative |
| JPH04173767A (en) * | 1990-11-02 | 1992-06-22 | Kanegafuchi Chem Ind Co Ltd | Production of 5,6-dihydroxy-3-oxohexanoic acid ester derivative |
| JPH06172256A (en) * | 1992-12-03 | 1994-06-21 | Kanegafuchi Chem Ind Co Ltd | Production of 3-hydroxybutyric acid derivative |
| JPH06209782A (en) * | 1993-01-12 | 1994-08-02 | Daicel Chem Ind Ltd | Production of optically active 4-halo-3-hydroxybutyric acid ester |
| JPH08336393A (en) * | 1995-04-13 | 1996-12-24 | Mitsubishi Chem Corp | Production of optically active gamma-substituted-beta-hydroxybutyric ester |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000009464A (en) | 2000-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH05331128A (en) | @(3754/24)r)-@(3754/24)-)-4-cyano-3-hydroxylactic acid t-butyl ester and its production | |
| JP3351563B2 (en) | Method for producing 3-hydroxybutyric acid derivative | |
| US5648534A (en) | Method of producing cis-1-aminoindan-2-ol | |
| KR100461561B1 (en) | (S) -3-carboxy-4-bromobutyric acid production method | |
| JP2002536356A (en) | Method for producing (R) -4-cyano-3-hydroxybutyrate | |
| WO2004005241A1 (en) | Process for producing optically active amide | |
| JP5448572B2 (en) | Acetyl compound, method for producing the acetyl compound, and method for producing a naphthol compound using the acetyl compound | |
| KR100332703B1 (en) | Method for preparing (S) -3,4-epoxybutyrate having optical activity | |
| CN111662287B (en) | Preparation of 5-tert-butyl-4-ethyl-3-methyl-dihydro-3H-imidazopyridine- (4H) -diformyl ester | |
| JP3731913B2 (en) | Process for producing cis-1-aminoindan-2-ol | |
| EP0339618B1 (en) | Method for preparing optically active 3,4-dihydroxy butyric acid derivatives | |
| JP2000063321A (en) | Production of long-chain beta-hydroxycarboxylic acid of high optical purity | |
| US6677465B2 (en) | Method for the enantioselective preparation of 3,3-diphenyl-2,3-epoxy propionic acid esters | |
| KR100699457B1 (en) | Process for preparing dibenzothiepin derivatives and intermediates thereof | |
| KR100440494B1 (en) | Method for preparing (S) -oxyracetam having optical activity | |
| JPH0124782B2 (en) | ||
| KR100449750B1 (en) | Process for the preparation of racemic alkyl 4-chloro-3-hydroxy butyrate | |
| US6175024B1 (en) | Synthesis of functionalized esters | |
| KR100525358B1 (en) | Method for the preparation of carboxyl benzotriazole alkyl ester | |
| AU2003268683A1 (en) | Process for production of an acetylenic compound | |
| KR20000021998A (en) | Process for preparing simvastatin and intermediate compound thereof | |
| RU2334736C1 (en) | Method of production of 3-phenoxy benzyl thiocyanate | |
| JPH06256254A (en) | Production of 2-alkyloxy-3,3,3-trifluoropropionic acid | |
| JP2002265461A (en) | Method for producing chromone derivative | |
| JPH09208566A (en) | Optically active oxazoline compound and asymmetric allyl oxidization reaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20100930 Year of fee payment: 7 |
|
| LAPS | Lapse due to unpaid annual fee |