JPH03220174A - Separation method for isomer - Google Patents
Separation method for isomerInfo
- Publication number
- JPH03220174A JPH03220174A JP1555290A JP1555290A JPH03220174A JP H03220174 A JPH03220174 A JP H03220174A JP 1555290 A JP1555290 A JP 1555290A JP 1555290 A JP1555290 A JP 1555290A JP H03220174 A JPH03220174 A JP H03220174A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- trans
- aziridine
- disubstituted cyclic
- cyclic compound
- 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
- 238000000926 separation method Methods 0.000 title claims abstract description 11
- 150000001541 aziridines Chemical class 0.000 claims abstract description 19
- 150000001923 cyclic compounds Chemical class 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 36
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 6
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 abstract description 5
- 235000002906 tartaric acid Nutrition 0.000 abstract description 5
- 239000011975 tartaric acid Substances 0.000 abstract description 5
- 125000004069 aziridinyl group Chemical group 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- 239000013543 active substance Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 238000005292 vacuum distillation Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 230000003993 interaction Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 230000003287 optical effect Effects 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- -1 sulfuric acid ester Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- OZDGMOYKSFPLSE-UHFFFAOYSA-N 2-Methylaziridine Chemical compound CC1CN1 OZDGMOYKSFPLSE-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000000382 dechlorinating effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- QXYIEFODFCALMU-UHFFFAOYSA-N ethyl 1-ethylaziridine-2-carboxylate Chemical compound CCOC(=O)C1CN1CC QXYIEFODFCALMU-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003952 β-lactams Chemical class 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〕
本発明はアジリジン誘導体の立体異性体の分離法に関す
るものであり、本発明の異性体分離方法は医薬を中心と
するファインケミストリーの分野で利用することができ
る。例えば、光学活性なアジリジン誘導体からは、光学
活性なポリアミン、光学活性な３−ピロロリン誘導体、
光学活性なβ−ラクタムを合成することができる。[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to a method for separating stereoisomers of aziridine derivatives, and the isomer separation method of the present invention can be used in the field of fine chemistry, mainly in medicine. can do. For example, optically active aziridine derivatives include optically active polyamines, optically active 3-pyrrololine derivatives,
Optically active β-lactams can be synthesized.
〔従来の技術及び発明が解決しようとする課題〕アジリ
ジン誘導体は、多種の反応によって容易に合成でき、ま
た反応性に冨むことから、合成中間体として工業的に重
要な位置をしめる。[Prior Art and Problems to be Solved by the Invention] Aziridine derivatives are industrially important as synthetic intermediates because they can be easily synthesized by various reactions and are highly reactive.
このアジリジン誘導体を通常の方法で化学合成した場合
には、これが不斉中心をもつ場合には、光学異性体の１
：ｌ比での混合物で、いわゆるラセミ体となり、また複
数の置換基を有するアジリジン環を有する場合には、そ
れらの置換基がシスあるいはトランスである幾何異性体
を生ずることもある。従って、これら幾何異性体を分離
精製し、あるいは光学異性体の混合物を光学分割して光
学活性体とする技術は、工業的に極めて重要である。な
かでも光学異性体については、その分離が特に困難であ
るが、近年医薬等の分野において光学異性体間で著しく
生理活性が異なる事例が見出され、一方の光学異性体含
量の大きい、いわゆる光学活性体の製造技術が重要視さ
れている、
例えば、光学活性アジリジン誘導体の入手という点から
見ると、以下の状況がある。−船釣なアジリジン誘導体
の合成は、モノエタノールアミンを硫酸エステル化し、
次いでアルカリ分解する方法、あるいは二塩化エチレン
をアンモニアで脱塩素して得る方法が工業的に用いられ
ている。しかし、これをエナンチオ選択的に行い、光学
活性体を得るためには、ある限られた基質に応用できる
手法が知られているにとどまる。従って、アミノ酸など
の天然に得られる光学活性化合物から、煩雑な多段階の
化学変換によって調製することが多い。この他、生化学
的な手法もあるが、応用範囲や到達できる光学純度、簡
便さに問題がある。When this aziridine derivative is chemically synthesized by a conventional method, if it has an asymmetric center, one of the optical isomers is
A mixture in the :l ratio results in a so-called racemate, and when the aziridine ring has a plurality of substituents, geometric isomers in which the substituents are cis or trans may occur. Therefore, techniques for separating and purifying these geometric isomers or optically resolving a mixture of optical isomers to obtain optically active forms are extremely important industrially. Among these, optical isomers are particularly difficult to separate, but in recent years cases have been found in the pharmaceutical field where the physiological activities of optical isomers are significantly different. For example, from the perspective of obtaining optically active aziridine derivatives, the following situation exists where the production technology of active substances is considered important. -Synthesis of aziridine derivatives is carried out by converting monoethanolamine into sulfuric acid ester.
Next, a method of alkaline decomposition or a method of dechlorinating ethylene dichloride with ammonia are used industrially. However, in order to perform this enantioselectively and obtain optically active substances, only a method that can be applied to a limited number of substrates is known. Therefore, they are often prepared from naturally occurring optically active compounds such as amino acids through complicated multi-step chemical transformations. In addition, there are biochemical methods, but there are problems with the range of application, the optical purity that can be achieved, and the simplicity.
本発明者らはアジリジン誘導体の立体異性体を分離する
ことの重要性を考え、鋭意検討を行った結果、ｔｒａｎ
ｓ−１＋ ２−二置換環状化合物とのタラスレート化合
物形成を利用することにより、上記立体異性体の分離が
効果的に達成されることを見出し、本発明に到達した。The present inventors considered the importance of separating stereoisomers of aziridine derivatives, and as a result of intensive studies, tran
The inventors have discovered that the separation of the stereoisomers can be effectively achieved by utilizing the formation of a talaslate compound with an s-1+ 2-disubstituted cyclic compound, and have arrived at the present invention.
即ち、本発明は、アジリジン誘導体の立体異性体の混合
物を、ｔｒａｎｓ−１＋ ２−二置換環状化合物を用い
て分離することを特徴とする異性体分離法に係わるもの
である。That is, the present invention relates to an isomer separation method characterized in that a mixture of stereoisomers of an aziridine derivative is separated using a trans-1+ 2-disubstituted cyclic compound.
本発明にいうアジリジン誘導体とは次の（１）式
〔式中、Ｒ１は水素原子、或いは炭素数１−１０からな
るグループを表し、Ｒ２は式−ＧＯＯＲ’ （Ｒ’は炭
素数１〜５からなるアルキル基）で示されるアルコキシ
カルボニル基、式−ＣＯＮ）ＩＲ’ （Ｒ’は炭素数１
〜５からなるアルキル基）で示されるＮ−アルキルカル
バモイル基、或いは炭素数１〜５からなるアルキル基を
表し、Ｒ３は水素原子、或いは炭素数１〜５からなるア
ルキル基を表す。〕で示されるものであり、本発明の方
法において、適当なｔｒａｎｓ−１２−二置換環状化合
物とタラスレート化合物を形成するものであれば、如何
なるものであってもよい。工業的に重要な化合物を例示
するなら、次の式（１−１）或いは（１−２）で表せる
ものが挙げられる。The aziridine derivative according to the present invention is defined by the following formula (1) [wherein R1 represents a hydrogen atom or a group consisting of 1 to 10 carbon atoms, and R2 represents the formula -GOOR'(R' is a group consisting of 1 to 5 carbon atoms] an alkoxycarbonyl group represented by the formula -CON)IR'(R' is a carbon number of 1
R3 represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms; ], and in the method of the present invention, any compound may be used as long as it forms a talaslate compound with an appropriate trans-12-disubstituted cyclic compound. Examples of industrially important compounds include those represented by the following formula (1-1) or (1-2).
Ｃ式中、Ｒ３は水素原子、或いは炭素数１〜１０からな
るグループを表し、Ｒ２は式−ＣＯＯＲ“（Ｒ”は炭素
数１〜５からなるアルキル基）で示されるアルコキシカ
ルボニル基、式−ＣＯＮＩ（Ｒ’ （Ｒ’は炭素数１〜
５からなるアルキル基）で示されるＮ−アルキルカルバ
モイル基、或いは炭素数１〜５からなるアルキル基を表
す。〕
Ｒ。In formula C, R3 represents a hydrogen atom or a group consisting of 1 to 10 carbon atoms, and R2 represents an alkoxycarbonyl group represented by the formula -COOR" (R is an alkyl group consisting of 1 to 5 carbon atoms), the formula - CONI(R'(R' is carbon number 1~
5) or an alkyl group having 1 to 5 carbon atoms. ] R.
〔式中、Ｒ３は水素原子、或いは炭素数１〜１０からな
るグループを表し、Ｒ２は式−ＣＯＯＲ’ （Ｒ’は炭
素数１〜５からなるアルキル基）で示されるアルコキシ
カルボニル基、式−ＣＯＮＨＲ’ （Ｒ’は炭素数１〜
５からなるアルキル、Ｉ）で示されるＮ−アルキルカル
バモイル基、或いは炭素数１〜５からなるアルキル基を
表し、Ｒ５は炭素数１〜５からなるアルキル基を表す。[In the formula, R3 represents a hydrogen atom or a group consisting of 1 to 10 carbon atoms, and R2 represents an alkoxycarbonyl group represented by the formula -COOR'(R' is an alkyl group consisting of 1 to 5 carbon atoms), the formula - CONHR'(R' is carbon number 1~
R5 represents an alkyl group having 5 carbon atoms, an N-alkylcarbamoyl group represented by I), or an alkyl group having 1 to 5 carbon atoms, and R5 represents an alkyl group having 1 to 5 carbon atoms.
〕
上記式（１−１）で表される化合物は、光学異性体の分
離に特に関心が持たれている。また式（１−２）で表さ
れる化合物は、光学異性体に加え、幾何異性体の分離に
も意味がある。] The compound represented by the above formula (1-1) is of particular interest in the separation of optical isomers. Moreover, the compound represented by formula (1-2) has meaning in separating not only optical isomers but also geometric isomers.
本発明でいうｔｒａｎｓ−１＋ ２−二置換環状化合物
とは、次の式（Ｉｆ）で示される。The trans-1+ 2-disubstituted cyclic compound as used in the present invention is represented by the following formula (If).
式中の環状構造は、原子数３個乃至７個より成るもので
あり、２個の炭素以外の構成原子は何であっても良い。The cyclic structure in the formula is composed of 3 to 7 atoms, and the constituent atoms other than the two carbon atoms may be any.
また該環状構造の形成に直接的にはあずからない置換基
を環上に有しても良い。Further, the ring may have a substituent that does not directly participate in the formation of the cyclic structure.
式（ｎ）中のＲは、炭素数３０以下より成る原子団であ
り、ペテロ原子を含んでも良い。R in formula (n) is an atomic group consisting of 30 or less carbon atoms, and may include a petero atom.
本発明に使用するｔｒａｎｓ−１＋ ２−二置換環状化
合物は、式（ｎ）で表される構造を有し、分割対象とな
るアジリジン誘導体とタラスレート化合物を形成する物
であれば、いかなるものであっても良い。但し、タラス
レート化合物の作り易さはその化学構造に大きく依存し
、好ましくはＲ中、あるいは環上に、更に剛直な環状原
子団を含むものである。また、Ｐ中には、更に、アジリ
ジン環と相互作用するための極性基を含むことが望まし
い。The trans-1+ 2-disubstituted cyclic compound used in the present invention may be any compound as long as it has a structure represented by formula (n) and forms a talaslate compound with the aziridine derivative to be resolved. It's okay. However, the ease with which a taluslate compound can be produced depends largely on its chemical structure, and preferably contains a more rigid cyclic atomic group in R or on the ring. Moreover, it is desirable that P further includes a polar group for interacting with the aziridine ring.
分離の対象が光学異性体である場合には、言うまでもな
く、該ｔｒａｎｓ−１，＋ ２−二置換環状化合物は光
学活性体でなければならない。光学活性な該化合物は、
いかなる方法で得てもよいが、酒石酸から誘導するのが
、その容易さと、原料の入手し易さにおいて、優れた方
法である（例えば実施例中で用いられている化合物上は
酒石酸より導かれたものである。）。When the object of separation is an optical isomer, it goes without saying that the trans-1,+2-disubstituted cyclic compound must be an optically active compound. The optically active compound is
Although it may be obtained by any method, derivation from tartaric acid is an excellent method in terms of ease and availability of raw materials (for example, the compounds used in the examples are derived from tartaric acid). ).
本発明の方法におけるタラスレート化合物の製造にはい
かなる方法を用いても良い。最も一般的な方法は、分割
対象となるアジリジン誘導体と、ｔｒａｎｓ−１＋ ２
−二置換環状化合物の適当量を溶媒に溶解し、温度変化
、溶媒蒸発、あるいは實溶媒の添加などによってクラス
レート化合物を析出させる。あるいは分離対象となるア
ジリジン誘導体の立体異性体の混合物自体を溶媒として
用いることもできる。また、両者が固体であっても、単
に混合によってタラスレート化合物を生成する場合もあ
る。このようにして得られた固体が、出発物質とは異な
った物理的性状（融点や結晶形など）を示し、両出発物
質を含むものであれば、タラスレート化合物を形成して
いることがわかる。該クラスレート化合物から、分離対
象とする化合物を回収する方法はいかなるものであって
も良いが、最も簡便なのは、減圧蒸留によって、沸点の
低い成分のみを別の容器に分離することである。こうし
た操作によって、目的とするアジリジン誘導体の中の特
定の異性体の含量を高めることができる。また、純度を
より高めたい場合には、タラスレート化合物の段階で再
結晶するのが良い方法であるが、回収後に再結晶操作を
適用できる場合もある。またクラスレート化合物の形成
によって、不要な異性体を除去することも可能である。Any method may be used to produce the talaslate compound in the method of the present invention. The most common method is to separate the aziridine derivative to be resolved and trans-1+ 2
- An appropriate amount of the disubstituted cyclic compound is dissolved in a solvent, and the clathrate compound is precipitated by temperature change, solvent evaporation, or addition of a real solvent. Alternatively, the mixture of stereoisomers of the aziridine derivative to be separated can itself be used as a solvent. Furthermore, even if both are solids, a Talaslate compound may be produced simply by mixing them. If the solid thus obtained exhibits physical properties (melting point, crystal shape, etc.) different from those of the starting materials and contains both starting materials, it is understood that it forms a taluslate compound. Any method may be used to recover the compound to be separated from the clathrate compound, but the simplest method is to separate only the components with a low boiling point into a separate container by vacuum distillation. By such operations, the content of a specific isomer in the desired aziridine derivative can be increased. In addition, if it is desired to further increase the purity, a good method is to recrystallize at the stage of the taluslate compound, but in some cases, a recrystallization operation can be applied after recovery. It is also possible to remove unwanted isomers by forming clathrate compounds.
本発明の方法がアジリジン誘導体の異性体分離に通して
いる理由は明らかでないが、本発明のｔｒａｎｓ−１＋
２−二置換環状化合物が、アジリジン環と相互作用し易
い大きさと極性を持っており、タラスレート化合物を形
成し易いものと考えられる。Although it is not clear why the method of the present invention allows isomer separation of aziridine derivatives, the trans-1+
It is considered that the 2-disubstituted cyclic compound has a size and polarity that make it easy to interact with the aziridine ring, and thus tends to form a talaslate compound.
本発明の方法に用いるｔｒａｎｓ−Ｌ２−二置換環状化
合物は、例えば酒石酸などから簡単に導くことができ、
また繰り返し利用することができる。従って本発明は工
業的に有用なアジリジン誘導体を高い純度で多量に供給
することを可能とするものである。The trans-L2-disubstituted cyclic compound used in the method of the present invention can be easily derived from tartaric acid, etc.
It can also be used repeatedly. Therefore, the present invention makes it possible to supply industrially useful aziridine derivatives in large amounts with high purity.
以下、実施例によって本発明を具体的に説明するが、本
発明がこれらに限定されるものでないことはいうまでも
ない。EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but it goes without saying that the present invention is not limited to these.
尚、本実施例中で用いたｔｒａｎｓ−１＋ ２−二置換
環状化合物は下式の構造を有し、酒石酸より誘導した光
学活性体である。The trans-1+ 2-disubstituted cyclic compound used in this example has the structure shown below and is an optically active compound derived from tartaric acid.
（Ｒ，Ｒ−（−）一体） （Ｒ，Ｒ−（−）一体）
実施例１
化合物１ａ ２．５ｇ （４，９ｍｍｏｌ）と次式で表
される１−エチル−２−エトキシカルボニルアジリジン
２１．４ｇ （９，８ｍｍｏｌ）をベンゼン２０ｄに加
熱溶解し、ヘキサン１０＠ｌを加えて室温で５時間放置
すると艮と（−）−２の１：１クラスレ一ト化合物が結
晶として１．９ｇ析出した（ａｌｐ１２７〜１３１℃、
〔α） Ｄ−９２，３＠（ＣＯ，２，ＣＨＣｈ）。(R, R-(-) integrated) (R, R-(-) integrated)
Example 1 2.5 g (4.9 mmol) of compound 1a and 21.4 g (9.8 mmol) of 1-ethyl-2-ethoxycarbonylaziridine represented by the following formula were dissolved in 20 d of benzene, and 10@l of hexane was dissolved. In addition, when it was left at room temperature for 5 hours, 1.9 g of a 1:1 clathreto compound of Ai and (-)-2 precipitated as crystals (alp 127-131°C,
[α) D-92,3@(CO,2,CHCh).
収率５９％）。yield 59%).
これを減圧下（２０ｎ＋Ｊｇ）、１５０″Ｃに加熱する
と（−）−２が０．２４ｇ留出した（ １００％ｅ、ｅ
、。When this was heated to 150''C under reduced pressure (20n+Jg), 0.24g of (-)-2 was distilled out (100% e, e
,.
（α） Ｉ、！２．３°（ｃ Ｏ，２，ＣＨＣｌｚ）、
収率３４％）。(α) I,! 2.3°(cO,2,CHClz),
yield 34%).
なお、光学純度はＮＦｌＲ法により決定した。Note that optical purity was determined by the NFIR method.
実施例２
実施例１と同様にして、化合物用を用いて、下記式で表
される２−メチルアジリジンユの分離を行った結果、（
→−）−主が収率３ｏ％（〔α〕。Example 2 In the same manner as in Example 1, 2-methylaziridinyl represented by the following formula was separated using a chemical compound. As a result, (
→-)-mainly yield 3o% ([α]).
＋４．２°（ｃ Ｏ，２，ＣＨＣｌ３）） で得られた
。+4.2°(cO,2,CHCl3)).
実施例３
実施例Ｉと同様にして、化合初動を用いて、下記式で表
されるｌ−エチル−２−メトキシカルボニルアジリジン
土の分離を行った結果、（＋）−土が収率４３％（６４
％ｅ、ｅ、、 （α） Ｄ＋９２．１”（ｃ Ｏ，２，
（ｊｌｃｈ））で得られた。Example 3 In the same manner as in Example I, l-ethyl-2-methoxycarbonylaziridine earth represented by the following formula was separated using compound initial reaction, and as a result, (+)-earth was obtained in a yield of 43%. (64
%e, e,, (α) D+92.1”(c O,2,
(jlch)).
ｔ
実施例４
実施例１と同様にして、化合物口を用いて、下記式で表
される１−ｎ−プロピル−２〜エトキシカルボニルアジ
リジに５−の分離を行った結果、（−）−５が収率３２
％（Ｃ（Ｘ ） ｎ １２２．０ ’（ｃ Ｏ，２，
ＣＨＣ［、））で得られた。t Example 4 In the same manner as in Example 1, 5- was separated into 1-n-propyl-2-ethoxycarbonylaziridi represented by the following formula using a compound port, and as a result, (-)- 5 has a yield of 32
%(C(X)n 122.0'(cO,2,
Obtained by CHC[,)).
−Ｐｒ
実施例５
実施例１と同様にして、化合物捷を用いて、下記式で表
される１〜ｎ−プロピル−２−メトキシカルボニルアジ
リジン旦の分離を行った結果、（−）−旦か収率４４％
（１００％ｅ、ｅ、、 〔α〕。-Pr Example 5 In the same manner as in Example 1, 1-n-propyl-2-methoxycarbonylaziridine hydroxide represented by the following formula was separated using compound separation. Yield 44%
(100% e, e, , [α].
−１２１，３°（ｃ Ｏ，２，ＣＨＣｌ＋））で得られ
た。-121,3° (cO,2,CHCl+)).
−Ｐｒ
実施例６
実施例１と同様にして、化合物すを用いて、下記式で表
される１−ｎ−プロピル−２−メトキシカルボニル−３
−メチルアジリジンユの分離を行った結果、（−）−７
が収率２８％（１００％”＝ （（ｒ ） ｏ ７８
．７°（ｃ Ｏ，２，ＣＨＣｌｔ））で得られた。-Pr Example 6 In the same manner as in Example 1, using the compound S, 1-n-propyl-2-methoxycarbonyl-3 represented by the following formula
-As a result of separating methylaziridine, (-)-7
yield 28% (100%” = ((r) o 78
．． 7°(c O,2,CHClt)).
−Ｐｒ
実施例８
実施例１と同様にして、化合物りを用いて、下記式で表
されるｌ−エチル−２−エチル力ルバモイルアジリジン
エの分離を行った結果、（−）−９が収率４２％（〔α
） 、−１０３，９°（ｃ Ｏ，２゜Ｃ）ＩｃＩ、ｌ）
）で得られた。-Pr Example 8 In the same manner as in Example 1, l-ethyl-2-ethyl rubamoyl aziridine represented by the following formula was separated using a compound. As a result, (-)-9 was Yield 42% ([α
) , -103,9°(c O,2°C)IcI,l)
) was obtained.
ｔ
実施例７
実施例１と同様にして、化合Ｔｈ１ａを用いて、下記式
で表される１−３−プロピル−２−メトキシカルボニル
−３−メチルアジリジ４１の分離を行った結果、（−）
−一旦一が収率３３％（２００％ｅ、ｅ、、 （α）
ｏ ’ ６０．０’ （ｃ Ｏ，２，ＣＨＣｌ＋））
Ｔ：得られた。t Example 7 In the same manner as in Example 1, 1-3-propyl-2-methoxycarbonyl-3-methylaziridi 41 represented by the following formula was separated using compound Th1a, and as a result, (-)
- Yield 33% (200% e, e, (α)
o '60.0' (c O,2,CHCl+))
T: Obtained.
−Ｐｒ
実施例９
実施例１と同様にして、化合物口を用いて、下記式で表
される１−ｎ−プロピル−２−ｎ−プロビル力ルバモイ
ルアジリジ４利の分離ヲ行った結果、（＋）−刊が収率
７４９ＡＮα） 、＋３１．２゜（ｃ Ｏ，２，ＣＨＣ
ｌ５））で得られた。-Pr Example 9 In the same manner as in Example 1, 1-n-propyl-2-n-propyl-rubamoyl aziridyl compound represented by the following formula was separated using a compound port. As a result, (+) - yield 749ANα), +31.2°(c O,2,CHC
15)).
カーＰｒCar Pr
Claims (1)
−１，２−二置換環状化合物を用いて分離することを特
徴とする異性体分離法。The mixture of stereoisomers of the aziridine derivative is trans
- An isomer separation method characterized by separation using a 1,2-disubstituted cyclic compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1555290A JP2831776B2 (en) | 1990-01-25 | 1990-01-25 | Isomer separation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1555290A JP2831776B2 (en) | 1990-01-25 | 1990-01-25 | Isomer separation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03220174A true JPH03220174A (en) | 1991-09-27 |
| JP2831776B2 JP2831776B2 (en) | 1998-12-02 |
Family
ID=11891935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1555290A Expired - Fee Related JP2831776B2 (en) | 1990-01-25 | 1990-01-25 | Isomer separation method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2831776B2 (en) |
-
1990
- 1990-01-25 JP JP1555290A patent/JP2831776B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2831776B2 (en) | 1998-12-02 |
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