JPH03279375A - Resolution of optically active 2-methylpiperazine - Google Patents
Resolution of optically active 2-methylpiperazineInfo
- Publication number
- JPH03279375A JPH03279375A JP8022090A JP8022090A JPH03279375A JP H03279375 A JPH03279375 A JP H03279375A JP 8022090 A JP8022090 A JP 8022090A JP 8022090 A JP8022090 A JP 8022090A JP H03279375 A JPH03279375 A JP H03279375A
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- methylpiperazine
- water
- solvent
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 title claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 150000007524 organic acids Chemical class 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 18
- 230000003287 optical effect Effects 0.000 abstract description 12
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 238000000605 extraction Methods 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 4
- VPZXBVLAVMBEQI-VKHMYHEASA-N Glycyl-alanine Chemical compound OC(=O)[C@H](C)NC(=O)CN VPZXBVLAVMBEQI-VKHMYHEASA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 108010079364 N-glycylalanine Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- JOMNTHCQHJPVAZ-RXMQYKEDSA-N (2r)-2-methylpiperazine Chemical compound C[C@@H]1CNCCN1 JOMNTHCQHJPVAZ-RXMQYKEDSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-YFKPBYRVSA-N (2s)-2-methylpiperazine Chemical compound C[C@H]1CNCCN1 JOMNTHCQHJPVAZ-YFKPBYRVSA-N 0.000 description 1
- VPZXBVLAVMBEQI-GSVOUGTGSA-N Gly-D-Ala Chemical compound [O-]C(=O)[C@@H](C)NC(=O)C[NH3+] VPZXBVLAVMBEQI-GSVOUGTGSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は光学活性２−メチルピペラジンの分割方法に関
するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for resolving optically active 2-methylpiperazine.
従来光学活性２−メチルピペラジンを得る方法としては
、
１、グリシル−（Ｓ）−アラニンを環化して得られる（
Ｓ）−３−メチル−２，５−ピペラジノンを還元して（
−）体を得、同様にグリシル−（Ｒ）−アラニンから（
＋）体を得る方法（ジャーナル・オブ・ケミカル・リサ
ーチ（シップシス）、４．１３３．１９８０）。Conventional methods for obtaining optically active 2-methylpiperazine include: 1. Obtained by cyclizing glycyl-(S)-alanine (
S)-3-methyl-2,5-piperazinone is reduced to (
-) body, and similarly from glycyl-(R)-alanine (
+) How to obtain a body (Journal of Chemical Research (Shipsys), 4.133.1980).
２、光学活性ホスト化合物との包接によって分割する方
法（ケミストリー・レターズ、３．５１３．１９８８）
。2. Method of separation by inclusion with an optically active host compound (Chemistry Letters, 3.513.1988)
.
３、光学活性酒石酸との２種のジアステレオマー塩を溶
媒から析出させる分割方法（特開平ｌ−１４９７７５）
。3. A separation method in which two types of diastereomeric salts with optically active tartaric acid are precipitated from a solvent (JP-A-149775)
.
等が知られている。etc. are known.
しかしながら、光学活性なグリシルアラニンを用いる方
法は、原料とする光学活性なグリシルアラニンが高価な
ため工業的な生産方法として満足できるものではない。However, the method using optically active glycylalanine is not satisfactory as an industrial production method because the optically active glycylalanine used as a raw material is expensive.
光学活性ホスト化合物としてキラルホストエース■（宇
部興産■）を用いる方法は、ホスト化合物が極めて高価
であるため工業的な生産方法とは言えない。また、光学
活性酒石酸とのジアステレオマー塩を溶媒から析出させ
る方法で、溶媒はメタノール、１プロパツール、２−プ
ロパツール、１−ブタノール。The method of using chiral host ace (trade name: Ube Industries, Ltd.) as an optically active host compound cannot be called an industrial production method because the host compound is extremely expensive. In addition, it is a method in which a diastereomer salt with optically active tartaric acid is precipitated from a solvent, and the solvents are methanol, 1-propatol, 2-propatol, and 1-butanol.
２−ブタノールおよびアセトン等から選ばれる少なくと
も１種の有機溶媒又はこれらの有機溶媒と水との混合溶
媒か好ましいとされている（特開平１−１４９７７５）
。しかし有機溶媒と水との混合溶媒から析出させる方法
は、２種のジアステレオマー塩の分別結晶化の効率か悪
く、例えば、比旋光度［αコ乙０＝＋６．０’又は−６
０° （ｃ＝１．００、ＥｔＯＨ）程度の光学純度の高
い２−メチルピペラジンを得るためには、５回以上もの
再結晶を繰り返さなければならず、収率も低く、光学活
性２−メチルピペラジンの工業的な生産方法として決し
て満足できるものではない。It is said that at least one organic solvent selected from 2-butanol, acetone, etc. or a mixed solvent of these organic solvents and water is preferable (Japanese Patent Laid-Open No. 1-149775).
. However, the method of precipitating from a mixed solvent of organic solvent and water has poor efficiency in fractional crystallization of two types of diastereomeric salts.
In order to obtain 2-methylpiperazine with a high optical purity of about 0° (c=1.00, EtOH), recrystallization must be repeated five or more times, the yield is low, and optically active 2-methylpiperazine This method is by no means satisfactory as an industrial production method for piperazine.
本発明は、気相法によって安価に製造される２−メチル
ピペラジンを出発原料として、光学活性２−メチルピペ
ラジンを高収率、簡便かつ工業的に得る方法を提供する
ものである。The present invention provides a method for obtaining optically active 2-methylpiperazine in high yield, simply and industrially using 2-methylpiperazine, which is produced at low cost by a gas phase method, as a starting material.
〔課題を解決するための手段及び方法３以上の問題点を
解決するために鋭意検討した結果、本発明を完成するに
至った。[Means and Methods for Solving the Problems As a result of intensive studies to solve the above problems, the present invention has been completed.
すなわち、本発明は（±）−２−メチルピペラジンと光
学活性な有機酸とを水だけを溶媒として反応させて２種
のジアステレオマー塩を形成させ、この２種のジアステ
レオマー塩の水に対する溶解度差を利用して相互に分割
し、中和後、有機溶媒で抽出することを特徴とする光学
活性２−メチルピペラジンの分割方法に関するものであ
る。That is, the present invention involves reacting (±)-2-methylpiperazine and an optically active organic acid using only water as a solvent to form two types of diastereomer salts, and The present invention relates to a method for resolving optically active 2-methylpiperazine, which is characterized by mutually resolving using the difference in solubility in 2-methylpiperazine and extracting with an organic solvent after neutralization.
驚くべきことに、本発明では水だけを溶媒として使用す
ることによって光学純度の極めて高い光学活性２−メチ
ルピペラジンを得られることが判明した。Surprisingly, it has been found that in the present invention, optically active 2-methylpiperazine with extremely high optical purity can be obtained by using only water as a solvent.
本発明によれば、使用する溶媒が水だけのため、極めて
安価に光学純度の高い光学活性２−メチルピペラジンを
得ることができる。According to the present invention, since only water is used as a solvent, optically active 2-methylpiperazine with high optical purity can be obtained at extremely low cost.
本発明の出発原料となる（±）−２−メチルピペラジン
は、気相法によって安価に得られるものである。（±）
−２−メチルピペラジンはラセミ体に限らず、どちらか
一方の光学活性体がその対掌体に対して等量以上含まれ
ているものでもよい。(±)-2-Methylpiperazine, which is the starting material of the present invention, can be obtained at low cost by a gas phase method. (±)
-2-Methylpiperazine is not limited to the racemic form, and may be one in which one of the optically active forms is contained in an amount equal to or more than that of its enantiomer.
本発明で使用される光学活性な有機酸は特に限定されな
いが、例えば、光学活性な酒石酸を用いる場合、工業的
にはＬ−酒石酸が容易に入手可能であり、安価な光学分
割剤として好ましい。The optically active organic acid used in the present invention is not particularly limited, but for example, when optically active tartaric acid is used, L-tartaric acid is easily available industrially and is preferred as an inexpensive optical resolution agent.
本発明方法は、まず（±）−２−メチルピペラジンと光
学活性な有機酸とを水に混合溶解して、（±）−２−メ
チルピペラジンと光学活性な有機酸との２種のジアステ
レオマー塩を形成させる。In the method of the present invention, first, (±)-2-methylpiperazine and an optically active organic acid are mixed and dissolved in water, and two types of diastereomerism are prepared by dissolving (±)-2-methylpiperazine and an optically active organic acid. form a mer salt.
（±）−２−メチルピペラジンに対し光学活性な有機酸
１〜１０倍モル、好ましくは２倍モル使用するのがよい
。It is preferable to use the optically active organic acid in an amount of 1 to 10 times, preferably 2 times, the mole of (±)-2-methylpiperazine.
ついで、形成された２種のジアステレオマー塩の水に対
する溶解度差を利用して相互に分割するには、水量・温
度・撹拌時間を調節し、撹拌下に結晶を析出させればよ
い。２種のジアステレオマー塩の水に対する溶解性が異
なるため、１種のジアステレオマー塩か優先的に析出す
る。Next, in order to separate the two formed diastereomer salts from each other by utilizing the difference in solubility in water, the amount of water, temperature, and stirring time may be adjusted to precipitate crystals while stirring. Since the two types of diastereomeric salts have different solubility in water, one type of diastereomeric salt preferentially precipitates.
分割の際に用いられる水の量及び温度・撹拌時間を適宜
選択することによって、光学活性２メチルピペラジンの
光学純度を調整することができる。The optical purity of optically active 2-methylpiperazine can be adjusted by appropriately selecting the amount of water, temperature, and stirring time used during the separation.
使用する水の量は、特に限定されないが、工業的には５
〜１０倍量が好ましい。また、難溶性塩を析出させる温
度も水の量によって０〜５０°Ｃくらいの範囲で可能で
あるか、操作上の簡便さから室温付近が好ましい。さら
に、撹拌時間は特に限定されないが、工業的には１〜７
２時間、好ましくは８〜４８時間の範囲がよい。The amount of water used is not particularly limited, but industrially 5
~10 times the amount is preferred. Further, the temperature at which the poorly soluble salt is precipitated can range from 0 to 50°C depending on the amount of water, or is preferably around room temperature for ease of operation. Furthermore, the stirring time is not particularly limited, but industrially it is 1 to 7 hours.
The time is preferably 2 hours, preferably 8 to 48 hours.
析出したジアステレオマー塩は濾過等の操作によって分
離する。得られたジアステレオマー塩は水溶性の塩基で
中和する。この際用いられる塩基としては、水酸化ナト
リウム、水酸化カリウム等が好ましい。The precipitated diastereomer salt is separated by an operation such as filtration. The resulting diastereomeric salt is neutralized with a water-soluble base. As the base used in this case, sodium hydroxide, potassium hydroxide, etc. are preferable.
中和した液は、有機溶媒、好ましくはベンゼン、トルエ
ン、酢酸エチル等の溶媒で抽出し、ついで常圧もしくは
減圧下で溶媒を留去し、必要ならばさらに蒸留すること
によって、光学純度の極めて高い光学活性２−メチルピ
ペラジンが得られる。The neutralized liquid is extracted with an organic solvent, preferably benzene, toluene, ethyl acetate, etc., then the solvent is distilled off under normal pressure or reduced pressure, and if necessary, further distillation is performed to obtain extremely high optical purity. Highly optically active 2-methylpiperazine is obtained.
一方、ジアステレオマー塩を濾別した後の濾液は、さら
に１／３〜２／３量まで濃縮し、析出した光学純度の低
いジアステレオマー塩を濾去する。この濾液を水酸化ナ
トリウム、水酸化カリウム等の塩基を加えて中和し、有
機溶媒、好ましくはベンゼン、トルエン、酢酸エチル等
の溶媒で抽出し、ついで常圧もしくは減圧下で溶媒を留
去し、必要ならばさらに蒸留することによって、初めに
得られた光学活性体の対掌体を極めて高い光学純度で得
ることができる。On the other hand, the filtrate after the diastereomeric salts have been filtered off is further concentrated to 1/3 to 2/3 of the volume, and the precipitated diastereomeric salts with low optical purity are filtered off. This filtrate is neutralized by adding a base such as sodium hydroxide or potassium hydroxide, extracted with an organic solvent, preferably a solvent such as benzene, toluene, or ethyl acetate, and then the solvent is distilled off under normal pressure or reduced pressure. By further distilling if necessary, the enantiomer of the optically active substance initially obtained can be obtained with extremely high optical purity.
本発明によれば、溶媒として水だけを使用し、１回の操
作だけで収率５０〜６０％で光学純度の極めて高い光学
活性２−メチルピペラジンを得ることができる。According to the present invention, optically active 2-methylpiperazine with extremely high optical purity can be obtained in a yield of 50 to 60% in a single operation using only water as a solvent.
以下に実施例を示し、本発明をさらに詳細に説明するが
、本発明は、これら実施例によって何ら制限を受けるも
のではない。EXAMPLES The present invention will be explained in more detail by way of Examples below, but the present invention is not limited in any way by these Examples.
実施例
水１．６１’ｊ：Ｌ−酒石酸（［（Ｚ］ ａ０＝＋１４
〜＋１５°） ６００ｇ （４，０ｍｏｌ）と（±）
−２−メチルピペラジン２００ｇ （２，０ｍｏｌ）を
室温下撹拌溶解し、さらに２４時間撹拌した。析出した
結晶を濾取し、水酸化ナトリウム水溶液で中和した。分
離してくる油状物をベンゼン抽出し、ベンゼン層を水酸
化ナトリウム水溶液で洗浄した。無水硫酸ナトリウムで
乾燥したのち溶媒を留去し、（＋）２−メチルピペラジ
ン５７ｇ（収率５７％）を得た。Example water 1.61'j: L-tartaric acid ([(Z] a0=+14
~+15°) 600g (4,0mol) and (±)
200 g (2.0 mol) of -2-methylpiperazine was dissolved under stirring at room temperature, and the mixture was further stirred for 24 hours. The precipitated crystals were collected by filtration and neutralized with an aqueous sodium hydroxide solution. The separated oil was extracted with benzene, and the benzene layer was washed with an aqueous sodium hydroxide solution. After drying over anhydrous sodium sulfate, the solvent was distilled off to obtain 57 g (yield 57%) of (+)2-methylpiperazine.
この比旋光度は、［α］８°＝＋６．２° （ｃ＝１．
００、ＥｔＯＨ）であった。This specific optical rotation is [α]8°=+6.2° (c=1.
00, EtOH).
さらに、上記の濾液を１７２量まで濃縮し、析出した結
晶を濾別し、この濾液を濃縮乾固した。Furthermore, the above filtrate was concentrated to 172 volumes, the precipitated crystals were filtered off, and the filtrate was concentrated to dryness.
得られた残渣を水酸化ナトリウム水溶液で中和して、分
離してくる油状物をベンゼン抽出し、ベンゼン層を水酸
化ナトリウム水溶液で洗浄した。無水硫酸ナトリウムで
乾燥したのち溶媒を留去し、（−）−２−メチルピペラ
ジン５３ｇ（収率５３％）を得た。The obtained residue was neutralized with an aqueous sodium hydroxide solution, the separated oil was extracted with benzene, and the benzene layer was washed with an aqueous sodium hydroxide solution. After drying over anhydrous sodium sulfate, the solvent was distilled off to obtain 53 g (-)-2-methylpiperazine (yield 53%).
この比旋光度は、［α］６°＝−４．８° （ｃ＝１０
０、ＥｔＯＨ）であった。This specific optical rotation is [α]6°=-4.8° (c=10
0, EtOH).
本発明の方法によって得られる光学活性２−メチルピペ
ラジンは、医薬品あるいは農薬の合成原料として有用な
化合物である。Optically active 2-methylpiperazine obtained by the method of the present invention is a compound useful as a synthetic raw material for pharmaceuticals or agricultural chemicals.
Claims (1)
酸とを水だけを溶媒として反応させて、２種のジアステ
レオマー塩を形成させ、この２種のジアステレオマー塩
の水に対する溶解度差を利用して相互に分割し、中和後
有機溶媒で抽出することを特徴とする光学活性２−メチ
ルピペラジンの分割方法。(1) (±)-2-Methylpiperazine and an optically active organic acid are reacted using only water as a solvent to form two types of diastereomer salts, and these two types of diastereomer salts are reacted with water. A method for splitting optically active 2-methylpiperazine, which comprises mutually splitting by utilizing a solubility difference, neutralized, and then extracted with an organic solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2080220A JP3032547B2 (en) | 1990-03-28 | 1990-03-28 | Resolution method of optically active 2-methylpiperazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2080220A JP3032547B2 (en) | 1990-03-28 | 1990-03-28 | Resolution method of optically active 2-methylpiperazine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03279375A true JPH03279375A (en) | 1991-12-10 |
| JP3032547B2 JP3032547B2 (en) | 2000-04-17 |
Family
ID=13712293
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2080220A Expired - Lifetime JP3032547B2 (en) | 1990-03-28 | 1990-03-28 | Resolution method of optically active 2-methylpiperazine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3032547B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995029170A1 (en) * | 1994-04-22 | 1995-11-02 | Koei Chemical Co., Ltd. | Process for producing optically active n-tert-butyl-2-piperazinecarboxamide and method of racemizing the amide |
| EP1384711A1 (en) * | 1996-06-13 | 2004-01-28 | SUMIKA FINE CHEMICALS Co., Ltd. | Optical resolution of a piperidine derivative |
| JP2004161749A (en) * | 2002-10-24 | 2004-06-10 | Toray Fine Chemicals Co Ltd | Method for producing optically active, nitrogen-containing compound |
-
1990
- 1990-03-28 JP JP2080220A patent/JP3032547B2/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995029170A1 (en) * | 1994-04-22 | 1995-11-02 | Koei Chemical Co., Ltd. | Process for producing optically active n-tert-butyl-2-piperazinecarboxamide and method of racemizing the amide |
| EP1384711A1 (en) * | 1996-06-13 | 2004-01-28 | SUMIKA FINE CHEMICALS Co., Ltd. | Optical resolution of a piperidine derivative |
| US6815548B2 (en) | 1996-06-13 | 2004-11-09 | Sumika Fine Chemicals Co., Ltd. | Process for preparing a piperidine derivative |
| JP2004161749A (en) * | 2002-10-24 | 2004-06-10 | Toray Fine Chemicals Co Ltd | Method for producing optically active, nitrogen-containing compound |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3032547B2 (en) | 2000-04-17 |
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