KR980009225A - Preparation method of D - (-) - 4-hydroxyphenylglycine - Google Patents
Preparation method of D - (-) - 4-hydroxyphenylglycine Download PDFInfo
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Abstract
본 발명은 D-(-)-4-히드록시페닐글리신의 제조방법에 관한 것으로서, DL-라세미 형태의 화합물로부터 광학활성을 갖는 D-(-)-4-히드록시페닐글리신을 제조함에 있어 분리시약을 이용한 비대칭변환과정에 초음파를 적용시켜 반응시간을 크게 단축하고 반응조건을 온화하게하며 높은 광학순도로 D-(-)-4-히드록시페닐글리신을 제조하는 방법에 관한 것이다.The present invention relates to a process for preparing D - (-) - 4-hydroxyphenylglycine, which comprises preparing D - (-) - 4-hydroxyphenylglycine having optical activity from a DL- (-) - 4-hydroxyphenylglycine with high optical purity by applying ultrasonic waves to the asymmetric conversion process using a separation reagent, thereby greatly shortening the reaction time and milder reaction conditions.
Description
본 발명은 D-(-)-4-히드록시페닐글리신의 제조방법에 관한 것으로서, 더욱 상세하게는 DL-라세미 형태의 화합물로부터 광학활성을 갖는 D-(-)-4-히드록시페닐글리신을 제조함에 있어 분리시약을 이용한 비대칭변환과정에 초음파를 적용시켜 반응시간을 크게 단축하고 반응조건을 온화하게하며 높은 광학순도를 D-(-)-4-히드록시페닐글리신을 제조하는 방법에 관한 것이다.More particularly, the present invention relates to a process for preparing D - (-) - 4-hydroxyphenylglycine from optically active D - (-) - 4-hydroxyphenylglycine (-) - 4-hydroxyphenylglycine by applying ultrasonic waves to the asymmetric conversion process using a separation reagent, thereby greatly shortening the reaction time, gentle reaction conditions, and high optical purity will be.
D-(-)-4-히드록시페닐글리신과 그 유도체는 대표적 아미노산으로 페니실린계 항생제인 아톡시실린, 세파드록실의 제조에 사용되는 중간체이다.D - (-) - 4-hydroxyphenylglycine and its derivatives are representative amino acids and intermediates used in the preparation of penicillin antibiotics such as atoxysyline and cephadoxyl.
종래에 D-(-)-4-히드록시페닐글리신을 합성하는 방법으로는, 일반적으로 DL-라세미 형태의 화합물을 합성하고, DL-라세미로부터 원하는 형인 D-형을 분리해내는 방법을 사용해온 바, 분리시 생물학적 또는 화학적 방법이 경쟁적으로 사용되어 있다.Conventionally, as a method for synthesizing D - (-) - 4-hydroxyphenylglycine, generally, a method of synthesizing a DL-racemic compound and isolating a desired D-form from DL- As used, biochemical or chemical methods have been used competitively in isolation.
생물학적 방법으로는 효소를 이용하는 방법을 사용하며, 화학적 방법으로는 광학활성을 갖는 적절한 분리시약을 사용하여 D-형의 이성질체와 염을 이룬 부분입체이성질체를 형성함으로써 용액상에서의 용해도차를 이용한 분별결정법으로 분리한 후 이를 가수분해에 의해 분리시약을 떼어냄으로써 원하는 D-(-)-4-히드록시페닐글리신을 얻는 방법이 있다.As a biological method, a method using an enzyme is used. In the chemical method, an appropriate optically active separation reagent is used to form a D-type isomer and a salt-forming diastereomer, whereby a fractionation determination method using the difference in solubility in solution And separating the separated reagent by hydrolysis to obtain the desired D - (-) - 4-hydroxyphenylglycine.
이러한 화학적 분리방법으로는 분리시약으로 R-브로모캠퍼술폰산을 사용하는 방법이 있는 바 「독일특허 공개 제 2540735 호(1976년)」, 이것은 시약자체의 흡습성때문에 D-(-)-4-히드록시페닐글리신을 분리해내기가 어려워 수율이 50% 정도로 낮은 단점이 있었다.As a chemical separation method, there is a method of using R-bromocamphorsulfonic acid as a separation reagent, as described in German Patent Publication No. 2540735 (1976). This is because of the hygroscopicity of the reagent itself, D- (-) - 4- There is a disadvantage in that the yield is as low as about 50% because it is difficult to separate and isolate Roxy phenylglycine.
더욱 발전된 형태로 영국특허 제 1,432,322 호에는 R-브로모캠퍼술폰산 암모늄염을 사용하고 여기에 무기산을 첨가하고 촉매량 정도의 아릴알데히드를 사용함으로서 DL-라세미중 D-형의 이성질체를 부분입체 이성질체화하고, 이와 더불어 원하지 않는 L-형을 다시 라세미화를 거쳐 D-형으로 비대칭변환하게하여 높은 광학순도의 화합물을 얻는 방법이 있다.In a further development, British Patent No. 1,432,322 discloses the use of R-bromocamphorsulfonic acid ammonium salt, the addition of mineral acid thereto and the use of a catalytic amount of arylaldehyde to diastereoisomerize the D-type isomer in the DL-racemate , And in addition, there is a method of obtaining an optically high-purity compound by asymmetrically converting an undesired L-form through a racemization to a D-form.
그러나, 이 방법에서도 높은 온도와 장시간의 반응조건을 부여해야만 한다.However, this method must also give high temperature and long reaction conditions.
다시말해 비대칭변환반응을 시킴에 있어 라세미화되기 위해서는 70~110℃의 높은 온도가 요구될 뿐만 아니라 원하는 D-형으로 완전히 변환되기 위해서는 일반적으로 20 시간 이상의 반응조건이 필요하다. 이와 같은 높은 온도와 장시간은 산업적으로 매우 불리한 점으로 작용한다.In other words, in order to make an asymmetric conversion reaction, a high temperature of 70-110 ° C. is required for the raceemization, and a reaction condition of 20 hours or more is generally required for complete conversion to the desired D-form. Such a high temperature and long time are industrially very disadvantageous.
본 발명은 상기와 같은 D-(-)-4-히드록시페닐글리신의 합성방법의 문제점을 해결하기 위해 분리시약으로 R-브로모캠퍼술폰산 알모늄염을 사용하고 반응도중에 초음파를 적용시킨 결과 고온과 장시간의 반응 조건을 극복하면서 높은 광학순도로 D-(-)-4-히드록시페닐글리신을 제조하는 방법을 제공하는데 그 목적이 있다.In order to solve the problems of the method for synthesizing D - (-) - 4-hydroxyphenylglycine as described above, the present invention uses an R-bromocamphorsulfonic acid ammonium salt as a separation reagent and applies ultrasound during the reaction, (-) - 4-hydroxyphenylglycine with high optical purity while overcoming long term reaction conditions.
본 발명은 DL-라세미 히드록시페닐글리신과 R-브로모캠퍼술폰산 알모늄염을 반응시켜 D-(-)-4-히드록시페닐글리신을 제조함에 있어서, 반응과정에 초음파를 적용시키는 것을 그 특징으로 한다.The present invention relates to a process for preparing D - (-) - 4-hydroxyphenylglycine by reacting DL-racemic hydroxyphenylglycine with an R-bromocamphosulfonic acid sulfonate in the presence of ultrasonic waves .
이와 같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
본 발명은 DL-라세미 히드록시페닐글리신을 분리시약을 이용하여 D-(-)-4-히드록시페닐글리신을 제조함에 있어서 반응촉진제로서 초음파를 적용시킨 D-(-)-4-히드록시페닐글리신의 제조방법에 관한 것이다.The present invention relates to a process for preparing D - (-) - 4-hydroxyphenylglycine by using DL-rac-hydroxyphenylglycine as a separation reagent, Phenylglycine. ≪ / RTI >
일반적으로 초음파를 이용한 효과로는 반응속도를 증가시켜 반응시간을 줄이고, 수율과 선택성을 향상시키며, 많은 겨우에 초음파는 보통의 반응에 요구되는 온도와 압력을 상당히 줄일 수 있어 산업적으로 매우 유용한 것으로 알려져 있고, 최근 다양한 반응에 초음파를 이용한 예가 있다.In general, the effect of using ultrasonic waves is believed to be very useful in industry because it increases reaction rate to reduce reaction time, improves yield and selectivity, and ultrasound can significantly reduce temperature and pressure required for ordinary reaction In recent years, there have been examples of using ultrasonic waves in various reactions.
예를들어, 카르복시산 에스테르의 가수분해 반응에 초음파를 이용하여 반응시간을 90분에서 10분으로 단축한 예가 있고 [Tetrahedron Letters No. 41, pp 3917], 주석수소화 환원반응에 초음파를 도입함으로써 온도를 50~100℃에서 0℃로 낮추는 효과를 나타내기도 한다 [J. Am. Chem. Soc., 6849(1989)]. 이같은 점은 전력상으로도 많은 잇점을 줄 수 있다. 그러나, 이는 통상의 화합물을 반응시키는 과정에서 반응여건과 입자 충돌횟수를 개선시킴으로 인해 얻어지는 것이다.For example, there is an example of shortening the reaction time from 90 minutes to 10 minutes by using ultrasonic waves in the hydrolysis reaction of the carboxylic acid ester [Tetrahedron Letters. 41, pp 3917], and an effect of lowering the temperature from 50 to 100 ° C to 0 ° C by introducing ultrasonic waves into the tin hydrogenation reduction reaction [J. Am. Chem. Soc., 6849 (1989)]. This can also provide many benefits in terms of power. However, this is obtained by improving the reaction conditions and the number of collision times in the process of reacting the conventional compound.
그러나, 본 발명에서는 이와는 달리 종래 시도된 바 없는 광학활성 화합물의 제조반응에 초음파를 적용시켜 새로운 매카니즘으로 반응온도 뿐아니라 반응시간을 개선한 것이다.However, the present invention improves the reaction time as well as the reaction temperature by applying ultrasonic waves to the reaction for preparing an optically active compound which has not been attempted conventionally.
본 발명에서는 DL-라세미 히드록시페닐글리신과 R-브로모캠퍼술폰산 알모늄염을 포함하는 불균일 반응으로 부분입체이성질체를 형성하는 반응에서 초음파를 반응촉진제로 사용한다. 본 발명에 있어서 D-(-)-4-히드록시페닐글리신의 제조는 통상의 조성 즉, DL-라세미 히드록시페닐글리신에 R-브로모캠퍼술폰산 알모늄염, 호아산 및 벤즈알데히드를 첨가하여 아세트산 용액에서 반응하는 바, 이때 초음파 처리를 한다.In the present invention, ultrasound is used as a reaction promoter in the reaction for forming diastereomers by heterogeneous reaction involving DL-racemic hydroxyphenylglycine and R-bromocamphosulfonic acid ammonium salt. In the present invention, the preparation of D - (-) - 4-hydroxyphenylglycine can be carried out by adding a conventional composition, that is, R-bromocamphorsulfonic acid ammonium salt, hyaluronic acid and benzaldehyde, to DL-racemic hydroxyphenylglycine, When it reacts in solution, ultrasonic treatment is performed at this time.
초음파는 20~80 kHz, 바람직하기로는 20~50 kHz의 주파수를 사용한다. 반응 매개물내에 도입된 초음파 에너지는 매개물을 지나면서 생성되는 공동화 현상 즉, 순간적인 압력차에 의해 발생되는 진공상태에 의해 화학적 및 물리화학적 영향을 주는데, 특히 핫-스팟(hot-spot) 이론에 따라 이러한 공동화 현상에 의해 거품이 생성되었다가 붕괴될 때 국부적으로 1,000℃ 이상의 높은 온도와 수천기압의 압력이 순간적으로 발생된다. 이렇게하여 발생된 극히 작은 크기의 거품은 반응하는 고체입자의 표면층을 기계적 영향으로 미세하게 부수게 되고, 반응속도를 빠르게하여 반응시간을 상당히 짧게 할 수 있다.The ultrasonic waves use a frequency of 20 to 80 kHz, preferably 20 to 50 kHz. The ultrasound energy introduced into the reaction medium has a chemical and physicochemical effect on the cavitation phenomenon generated by the medium, that is, the vacuum state caused by the instantaneous pressure difference. Especially, according to the hot-spot theory When the bubbles are generated and collapsed by this cavitation phenomenon, a high temperature of 1,000 ° C or more and a pressure of several thousand atmospheres are instantly generated locally. The extremely small size bubbles generated in this way cause the surface layer of the reacting solid particles to be finely crushed by mechanical effects, and the reaction speed can be increased to shorten the reaction time considerably.
또한, 초음파를 이용한 결과 낮은 온도에서도 라세미화가 가능하게 되었다. 이것은 외부적으로는 열이 주어지지 않았지만, 초음파 에너지에 의해 극히 순간적이고 극히 국부적으로 발생되는 높은 온도와 압력으로 인하여 반응에 필요한 전이상태 에너지 수준에 쉽게 도달할 수 있게 되었기 때문이다.In addition, ultrasound has made it possible to achieve racemization even at low temperatures. This is because heat is not externally applied, but because of the high temperature and pressure generated by ultrasonic energy very instantly and extremely locally, it is possible to easily reach the transition state energy level required for the reaction.
여기서 반응계의 온도는 여전히 주어진 외부온도를 유지한다.Where the temperature of the reaction system still maintains the given external temperature.
이처럼 D-(-)-4-히드록시페닐글리신의 비대칭합성변환 기술에 초음파를 도입한 결과 반응온도를 높여 주고 반응시간을 현저히 단축시키는 효과를 얻었다.As a result of introducing ultrasonic wave into the asymmetric synthesis conversion technique of D - (-) - 4-hydroxyphenylglycine, the reaction temperature was raised and the reaction time was remarkably shortened.
반응온도를 70℃로 동일하게 유지한 경우 반응시간을 종래에는 20 시간이었던 것을 3 시간 이내로 단축시켜 약 6배 이상의 반응시간 단축효과가 나타났고, 반응온도를 30℃로 하는 경우에도 약 7 시간으로서 약 3배의 반응시간 단축효과를 얻을 수 있다.When the reaction temperature was maintained at 70 캜, the reaction time was reduced from about 20 hours to about 3 hours by about 6 times, and about 7 hours even when the reaction temperature was set at 30 캜 A reaction time shortening effect of about 3 times can be obtained.
한편, 반응조건을 향상시키면서도 높은 광학순도를 계속 유지해야 하는데, 같은 조건하에서 초음파를 사용하지 않는 경우보다 훨씬 높은 광학순도를 보인다.On the other hand, it is necessary to keep the high optical purity while improving the reaction condition, and it shows much higher optical purity than the case of not using ultrasonic under the same conditions.
이하, 본 발명을 실시예에 의거하여 상세히 설명하면 다음과 같은 바, 본 발명이 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to the following examples, but it should be understood that the invention is not construed as being limited thereto.
[실시예 1][Example 1]
초음파(20~50kHz) 발생기에 물을 절반기량 채웠다.An ultrasonic (20-50 kHz) generator was filled with half the water.
100 ㎖ 삼각플라스크에 DL-라세미 히드록시페닐글리신 0.50 g(2.99mmol)과 R-브로모캠퍼술폰산 알모늄염 1.03 g(3.14mmol)을 넣고 초음파 발생기에 장치하였다. 용매로 정제한 아세트산 10㎖를 가하고, 진한 황산 108 ㎕(2.10 mmol), 벤즈알데히드 30.5 ㎕(1.74 mmol)을 순차적으로 첨가하였다. 승온하여 70℃를 유지하면서 3 시간 동안 반응하였다. 그 다음, 반응액을 상온으로 냉각하고 여과한 후 아세트산 5㎖로 세척하고 80℃에서 건조시켜 흰색의 D-(-)-4-히드록시페닐글리신·R-브로모캠퍼술폰산의 부분입체이성질체염 0.36 g(94%)을 얻었다.0.50 g (2.99 mmol) of DL-rahydroxyphenylglycine and 1.03 g (3.14 mmol) of R-bromocamphorsulfonic acid sulfonic acid sulfonate were placed in a 100 mL Erlenmeyer flask and placed in an ultrasonic generator. 10 ml of purified acetic acid as a solvent was added, and 108 μl (2.10 mmol) of concentrated sulfuric acid and 30.5 μl (1.74 mmol) of benzaldehyde were added sequentially. The reaction was allowed to proceed for 3 hours while maintaining the temperature at 70 캜. Then, the reaction solution was cooled to room temperature, filtered, washed with 5 ml of acetic acid and dried at 80 ° C to obtain a diastereomeric salt of D - (-) - 4-hydroxyphenylglycine.R-bromocamphorsulfonic acid 0.36 g (94%) was obtained.
이때의 광학 D/L 비율은 99.3 / 0.7이고, 녹는점은 243~245℃이다.The optical D / L ratio at this time is 99.3 / 0.7 and the melting point is 243 ~ 245 ° C.
[실시예 2][Example 2]
초음파(20~50kHz) 발생기에 물을 절반기량 채웠다.An ultrasonic (20-50 kHz) generator was filled with half the water.
100 ㎖ 삼각플라스크에 DL-라세미 히드록시페닐글리신 0.50 g(2.99mmol)과 R-브로모캠퍼술폰산 알모늄염 1.03 g(3.14mmol)을 넣고 초음파 발생기에 장치하였다. 용매로 정제한 아세트산 10㎖를 가하고, 진한 황산 108 ㎕(2.10 mmol), 벤즈알데히드 30.5 ㎕(1.74 mmol)을 순차적으로 첨가하였다. 승온하여 50℃를 유지하면서 5 시간 동안 반응하였다. 그 다음, 반응액을 상온으로 냉각하고 여과한 후 아세트산 5㎖로 세척하고 80℃에서 건조시켜 흰색의 D-(-)-4-히드록시페닐글리신·R-브로모캠퍼술폰산의 부분입체이성질체염 1.32 g(92%)을 얻었다.0.50 g (2.99 mmol) of DL-rahydroxyphenylglycine and 1.03 g (3.14 mmol) of R-bromocamphorsulfonic acid sulfonic acid sulfonate were placed in a 100 mL Erlenmeyer flask and placed in an ultrasonic generator. 10 ml of purified acetic acid as a solvent was added, and 108 μl (2.10 mmol) of concentrated sulfuric acid and 30.5 μl (1.74 mmol) of benzaldehyde were added sequentially. The reaction was continued for 5 hours while the temperature was raised to 50 < 0 > C. Then, the reaction solution was cooled to room temperature, filtered, washed with 5 ml of acetic acid and dried at 80 ° C to obtain a diastereomeric salt of D - (-) - 4-hydroxyphenylglycine.R-bromocamphorsulfonic acid 1.32 g (92%) was obtained.
이때의 광학 D/L 비율은 99.0 / 1.0이고, 녹는점은 243~245℃이다.The optical D / L ratio at this time is 99.0 / 1.0 and the melting point is 243 ~ 245 ° C.
[실시예 3][Example 3]
실시예 1에서와 같은 반응조건으로 반응하되, 다만 온도를 30℃로 하여 7시간 반응시킨 결과, 91% 수율의 D-(-)-4-히드록시페닐글리신·R-브로모캠퍼술폰산의 부분입체이성질체염 1.3 g을 얻었으며, 광학 D/L 비율은 98.0 / 2.0이고, 녹는점은 243~245℃이다.The reaction was carried out under the same reaction conditions as in Example 1 except that the reaction was carried out at a temperature of 30 ° C for 7 hours. As a result, a portion of D - (-) - 4-hydroxyphenylglycine.R-bromo camphorsulfonic acid 1.3 g of the stereoisomer salt was obtained, the optical D / L ratio was 98.0 / 2.0, and the melting point was 243 ~ 245 ° C.
[비교예 1][Comparative Example 1]
3구 100㎖ 둥근바닥 플라스크에 DL-라세미 히드록시페닐글리신 1.0 g(6.0mmol)과 R-브로모캠퍼술폰산 알모늄염 2.05 g(6.27 mmol)을 넣었다. 용매로 정제한 아세트산 13㎖를 가하고, 진한 황산 216 ㎕(4.2 mmol), 벤즈알데히드 61.0 ㎕(3.48 mmol)을 순차적으로 첨가하였다. 승온하여 90℃를 유지하면서 20 시간 동안 반응시켰다. 그 다음, 반응액을 상온으로 냉각하고 여과한 후 아세트산 5㎖로 세척하고 80℃에서 건조시켜 흰색의 D-(-)-4-히드록시페닐글리신·R-브로모캠퍼술폰산의 부분입체이성질체염 2.69 g(92%)을 얻었다.1.0 g (6.0 mmol) of DL-raisylhydroxyphenylglycine and 2.05 g (6.27 mmol) of R-bromocamphorsulfonic acid ammonium salt were placed in a three-necked 100 mL round bottom flask. 13 ml of purified acetic acid as a solvent was added, 216 μl (4.2 mmol) of concentrated sulfuric acid and 61.0 μl (3.48 mmol) of benzaldehyde were added sequentially. The reaction was allowed to proceed for 20 hours while keeping the temperature at 90 캜. Then, the reaction solution was cooled to room temperature, filtered, washed with 5 ml of acetic acid and dried at 80 ° C to obtain a diastereomeric salt of D - (-) - 4-hydroxyphenylglycine.R-bromocamphorsulfonic acid 2.69 g (92%) was obtained.
이때의 광학 D/L 비율은 99.0 / 1.0으로 측정되었다.The optical D / L ratio at this time was measured as 99.0 / 1.0.
[비교예 2][Comparative Example 2]
상기 비교예 1과 동일하게 실시하되 70 ℃에서 20시간 동안 반응시켰다.The reaction was carried out in the same manner as in Comparative Example 1, but the reaction was carried out at 70 ° C for 20 hours.
그 결과 D-(-)-4-히드록시페닐글리신·R-브로모캠퍼술폰산의 부분입체이성질체염 2.6 g(91%)을 얻었으며, 이때의 광학 D/L 비율은 99.0 / 1.0이었다.As a result, 2.6 g (91%) of a diastereomeric salt of D - (-) - 4-hydroxyphenylglycine R-bromocamphorsulfonic acid was obtained, and the optical D / L ratio was 99.0 / 1.0.
[비교예 3][Comparative Example 3]
상기 비교예 1과 동일하게 실시하되 50 ℃에서 5시간 동안 반응시켰다. 그 결과 D-(-)-4-히드록시페닐글리신·R-브로모캠퍼술폰산의 부분입체이성질체염 2.57 g(90%)을 얻었으며, 이때의 광학 D/L 비율은 68.0 / 28.0이었다.The reaction was carried out in the same manner as in Comparative Example 1 except that the reaction was carried out at 50 ° C for 5 hours. As a result, 2.57 g (90%) of the diastereomeric salt of D - (-) - 4-hydroxyphenylglycine.R-bromocamphorsulfonic acid was obtained, and the optical D / L ratio at this time was 68.0 / 28.0.
상기 실시예 1~3의 반응조건 및 결과를 요약하면 다음 표 1에 나타낸 바와 같다.The reaction conditions and results of Examples 1 to 3 are summarized in Table 1 below.
[표 1][Table 1]
상기 실시예 1과 비교예 2의 경우, 70℃의 동일한 온도조건을 주었을 때 초음파를 가하지 않은 비교예 2는 반응시간이 20시간인 반면 초음파를 적용한 실시예 1의 경우는 3 시간으로 6배 이상의 반응시간 단축의 효과를 볼 수 있었고, 높은 광학순도를 보였다. 또한, 실시예 1과 비교예 3의 경우, 반응온도와 시간을 동일하게 주었을 때 초음파의 적용여부에 따라 광학순도에 있어 현격한 차이를 보였다.In the case of Example 1 and Comparative Example 2, the reaction time was 20 hours in Comparative Example 2 in which no ultrasonic wave was applied while the same temperature condition was 70 ° C, whereas in Example 1 in which ultrasonic waves were applied, the reaction time was 6 times or more The reaction time was shortened and the optical purity was high. In the case of Example 1 and Comparative Example 3, when the reaction temperature and time were the same, there was a remarkable difference in optical purity depending on whether ultrasonic waves were applied or not.
상기의 결과로부터 본 발명에서와 같이 초음파는 광학활성을 갖는 물질의 반응에 유효하며, 특히 D-(-)-4-히드록시페닐글리신의 비대칭변환반응에 매우 효율적인 결과를 줌을 알 수 있다.From the above results, it can be seen that the ultrasonic wave is effective for the reaction of the optically active substance as in the present invention, and it is very effective for the asymmetric conversion reaction of D - (-) - 4-hydroxyphenylglycine.
Claims (2)
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| KR1019960031989A KR980009225A (en) | 1996-07-31 | 1996-07-31 | Preparation method of D - (-) - 4-hydroxyphenylglycine |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR19980059276A (en) * | 1996-12-31 | 1998-10-07 | 박영구 | Method for producing racemic DL-phenylglycine using ultrasound |
| KR100461562B1 (en) * | 1996-12-31 | 2005-04-06 | 삼성정밀화학 주식회사 | Method for racemization of optically active phenylglycine |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5132541A (en) * | 1974-09-12 | 1976-03-19 | Fujisawa Pharmaceutical Co | Dll22 * 44 hidorokishifueniru * gurishinnokogakubunkatsuho |
| JPS57146744A (en) * | 1981-03-07 | 1982-09-10 | Hiroyuki Nohira | Optical resolving method of dl-m-hydroxyphenylglycine |
| US4350641A (en) * | 1980-01-25 | 1982-09-21 | Basf Aktiengesellschaft | 4-Tert.-butoxyphenylglycinonitrile and the preparation of D-(-)- and L-(+)-4-hydroxyphenylglycine |
| KR920014764A (en) * | 1991-01-31 | 1992-08-25 | 아이리인 티이 브라운 | Method for decomposing α-amino acid stereoisomer or mixture of salts thereof |
| JPH05163216A (en) * | 1990-03-21 | 1993-06-29 | Gerard Kessels | Method of preparing d-(-)-4-hydroxyphenylglycine and l-(+)-4-hydroxyphenylglycine from d,l-4-hydroxyphenyl- glycine |
-
1996
- 1996-07-31 KR KR1019960031989A patent/KR980009225A/en not_active Application Discontinuation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5132541A (en) * | 1974-09-12 | 1976-03-19 | Fujisawa Pharmaceutical Co | Dll22 * 44 hidorokishifueniru * gurishinnokogakubunkatsuho |
| US4350641A (en) * | 1980-01-25 | 1982-09-21 | Basf Aktiengesellschaft | 4-Tert.-butoxyphenylglycinonitrile and the preparation of D-(-)- and L-(+)-4-hydroxyphenylglycine |
| JPS57146744A (en) * | 1981-03-07 | 1982-09-10 | Hiroyuki Nohira | Optical resolving method of dl-m-hydroxyphenylglycine |
| JPH05163216A (en) * | 1990-03-21 | 1993-06-29 | Gerard Kessels | Method of preparing d-(-)-4-hydroxyphenylglycine and l-(+)-4-hydroxyphenylglycine from d,l-4-hydroxyphenyl- glycine |
| KR920014764A (en) * | 1991-01-31 | 1992-08-25 | 아이리인 티이 브라운 | Method for decomposing α-amino acid stereoisomer or mixture of salts thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR19980059276A (en) * | 1996-12-31 | 1998-10-07 | 박영구 | Method for producing racemic DL-phenylglycine using ultrasound |
| KR100461562B1 (en) * | 1996-12-31 | 2005-04-06 | 삼성정밀화학 주식회사 | Method for racemization of optically active phenylglycine |
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