JPS6354341A - Optical resolution process - Google Patents
Optical resolution processInfo
- Publication number
- JPS6354341A JPS6354341A JP19813486A JP19813486A JPS6354341A JP S6354341 A JPS6354341 A JP S6354341A JP 19813486 A JP19813486 A JP 19813486A JP 19813486 A JP19813486 A JP 19813486A JP S6354341 A JPS6354341 A JP S6354341A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- cis
- eba
- ethylbenzylamine
- 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
- 230000003287 optical effect Effects 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims description 15
- 239000002253 acid Substances 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 239000013078 crystal Substances 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract 2
- AQFLVLHRZFLDDV-UHFFFAOYSA-N 1-phenylpropan-1-amine Chemical compound CCC(N)C1=CC=CC=C1 AQFLVLHRZFLDDV-UHFFFAOYSA-N 0.000 claims description 9
- 150000007513 acids Chemical class 0.000 claims description 4
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000011081 inoculation Methods 0.000 claims description 3
- -1 (+)-α-ethyl bezylamine Chemical compound 0.000 claims description 2
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-M cyclohexanecarboxylate Chemical compound [O-]C(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-M 0.000 claims 3
- PUANNVQABXUYKU-NEPJUHHUSA-N (1r,2s)-2-benzamidocyclohexane-1-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCC[C@@H]1NC(=O)C1=CC=CC=C1 PUANNVQABXUYKU-NEPJUHHUSA-N 0.000 claims 2
- XKEFYDZQGKAQCN-UHFFFAOYSA-N 1,3,5-trichlorobenzene Chemical compound ClC1=CC(Cl)=CC(Cl)=C1 XKEFYDZQGKAQCN-UHFFFAOYSA-N 0.000 claims 2
- AJPOREWXLFKIOC-UHFFFAOYSA-N benzamide;cyclohexanecarboxylic acid Chemical class NC(=O)C1=CC=CC=C1.OC(=O)C1CCCCC1 AJPOREWXLFKIOC-UHFFFAOYSA-N 0.000 claims 1
- HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 7
- 238000002425 crystallisation Methods 0.000 abstract description 5
- VGKZBAMIYUHSMU-UHFFFAOYSA-N 4-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylic acid Chemical class OC(=O)C1CCC(NC(=O)N(CCCl)N=O)CC1 VGKZBAMIYUHSMU-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002585 base Substances 0.000 abstract description 4
- 230000008025 crystallization Effects 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940116298 l- malic acid Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 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、α−エチルベンジルアミン（以下ＥＢＡと略
記する）及び／又は、シス−２−ペンズアミドシクロヘ
キサンカルボン酸（以下ｅｉｓ酸と略記する）の光学分
割法に関するものである。ＥＢＡ’は、専ら化学的合成
法によって製造される化合物であり、その用途として、
光学活性体がラセミ酸の光学分割剤として期待されてい
る。一方、ｃｉｓ酸は、その光学活性ｆ、１勤＜ラセミ
塩基の光学分割剤として有用な化合物であり、特に、（
±）−ａ−ナフチルエチルアミンの光学分割に有用であ
る（特開昭５８−２４５４５）ことから、その活性体を
容易に得る方）去の開発が望まれている。Detailed Description of the Invention (Industrial Application Field) The present invention relates to α-ethylbenzylamine (hereinafter abbreviated as EBA) and/or cis-2-penzamide cyclohexanecarboxylic acid (hereinafter abbreviated as eis acid). ) is related to the optical resolution method. EBA' is a compound produced exclusively by chemical synthesis methods, and its uses include:
The optically active form is expected to be used as an optical resolution agent for racemic acid. On the other hand, cis acid is a compound useful as an optical resolving agent for optical activity f, 1st function < racemic base, especially (
Since it is useful for the optical resolution of ±)-a-naphthylethylamine (JP-A-58-24545), it has been desired to develop a method to easily obtain its active form.
（従来技術及び問題点）
従来、（±）−ＥＢＡの光学分割法としては、ｌ−リン
ゴ酸を光学分割剤として用いる方法［Ａ、Ｊ。(Prior Art and Problems) Conventionally, as an optical resolution method for (±)-EBA, a method using l-malic acid as an optical resolution agent [A, J.
Ｌｉｔｔｌｅら、ジャーナルオブケミカルソサイテイー
（Ｊ、Ｃｈｅｍ、Ｓｏｅ、）、３３６（１９４０）］、
あるいは］アセチルブロモーＬ−チロシを用いる方法［
Ｈ，Ｄ、ＤｅＷｉｔｔら、ジャーナルオブアメリカンケ
ミカルソサイティー（Ｊ、Ａｍ、Ｃｈｅｒｎ−８ｏｅ、
）、７３．５７８２（，１９５１月が報告されている、
しかしながらこれらの方法は、分割剤として天然に存在
し、比較的容易に入手し得る光学活性酸を利用したもの
であり、純粋な光学活性体を得るためには再結晶を繰り
返す必要があり収率も高くないなどの欠点があった。従
来、ｅｉｓ酸の活性体を得る方法としては、ｅｉｓ酸の
ベンジルアミン塩を優先品出させる方法が知られている
（特許公報昭５９−３４７０）。Little et al., Journal of Chemical Society, 336 (1940)],
Alternatively] a method using acetylbromo L-tyrosi [
H, D, DeWitt et al., Journal of American Chemical Society (J, Am, Chern-8oe,
), 73.5782 (, 1951 is reported,
However, these methods utilize naturally occurring and relatively easily available optically active acids as resolving agents, and in order to obtain pure optically active substances, it is necessary to repeat recrystallization, resulting in low yields. It also had some drawbacks, such as not being expensive. Conventionally, as a method for obtaining an activated form of eis acid, a method is known in which a benzylamine salt of eis acid is prioritized (Patent Publication No. 59-3470).
（問題点を解決するための手段）
本発明者らは、（±）−ＥＢＡおよび（±）−ｃｉｓ酸
の光学活性体を得るべく種々検討した結果、（±）−Ｅ
ＢＡと（±）−ｅｉｓ酸の塩が一対の難溶性塩の混合物
、すなわち（＋）−ＥＢＡ ・（−）−ｅｉｓ酸塩と（
−）−ＥＢＡ −（＋）−ｅｉｓ酸ｊｊＫのラセミ混合
物として存在することを発見し、更に（±）−ＥＢＡと
（±）−ｅｉｓ酸の過修和溶液から、（＋）−ＥＢＡ
ｌ ）−ｅｉｓ酸塩あるいは、（−）−ＥＢＡ −（
＋ ）−ｅｉｓ酸塩のＥｉｔ溶性塩を優先的に晶出させ
ると高い分割効率で高光学純度のＥＢＡとｅｉｓ酸の塩
を得ることができることを見出し、本発明を完成するに
至った。(Means for Solving the Problems) As a result of various studies to obtain optically active forms of (±)-EBA and (±)-cis acid, the present inventors found that (±)-EBA
The salt of BA and (±)-eis acid is a mixture of a pair of sparingly soluble salts, namely (+)-EBA, (-)-eis acid salt and (
-)-EBA was found to exist as a racemic mixture of (+)-eis acid jjK, and furthermore, from a supermodified solution of (±)-EBA and (±)-eis acid, (+)-EBA
l)-eis acid salt or (-)-EBA-(
The present inventors have discovered that a salt of EBA and eis acid with high optical purity can be obtained with high separation efficiency by preferentially crystallizing the Eit-soluble salt of the +)-eis acid salt, and have completed the present invention.
即ち本発明は、（±）−ＥＢＡおよび（±）−ｅｉｓ酸
を含有する溶液から、（＋）−ＥＢＡ・（−）−ｅｉｓ
酸塩あるいは、（−）−ＥＢＡ・（＋）−ｅｉｓ酸塩を
交互に優先品出させることに特徴を有する方法であり品
出した塩を固液分離し、次いでこれらの塩を遊離して（
＋）−あるいは（−）−ＥＢＡと（−）−あるいは（＋
）−ｅｉｓ酸とに分離することにより、光学活性なＥＢ
Ａおよびｃｉｓ酸が同時に得られるという画期的な分割
方法であり、この方法によれば（±）−ＥＢＡと（±）
−ｅｉｓ酸を円滑にかつ効率良く、しかも連続的に光学
分割できるという優れた効果を生ずるものである。更に
本発明は、前記（±）−ＡＢＡおよび（±）−ｃｉｓ酸
を含有する溶液中に、（＋）−ＥＢＡ、（−）−ＥＢＡ
、（＋）−ｅｉｓ酸及び（−）−ｃｉｓ酸のうち少なく
とも１種の）負度を高めて実施する方法をも含む。That is, the present invention provides (+)-EBA・(−)-eis acid from a solution containing (±)-EBA and (±)-eis acid.
This method is characterized by preferentially producing salts of acid or (-)-EBA/(+)-eis salts alternately. The produced salts are subjected to solid-liquid separation, and then these salts are liberated. (
+)-or (-)-EBA and (-)-or (+
)-eis acid and optically active EB.
This is an innovative separation method that allows A and cis acids to be obtained simultaneously, and according to this method, (±)-EBA and (±)
-Eis acid can be optically resolved smoothly, efficiently, and continuously, which is an excellent effect. Furthermore, the present invention provides that (+)-EBA, (-)-EBA and
, (+)-eis acid, and (-)-cis acid).
本発明を実施するに当たっては、４ｔに（±）−ＥＢＡ
と（±）−ｃｉｓ酸を含有する過餞和溶液に、（＋）−
ＥＢＡ −（−）−ｃｉｓ酸塩あるいは（−）−ＥＢＡ
−（＋ ）−ｃｉｓ酸塩の種結晶を接種する単純な交
互イ憂先晶出法を適用することも可能であるが、更に、
例えば、（±）−ＥＢＡ（あるいは（±）−ｃｉｓ酸）
を分割する場合、ｃｉｓ酸（あるいはＥＢＡ）の光学活
性ｆトとラセミ体の混合物を用いることにより、極めて
円滑かつ効率良く（±）−ＥＢＡ（あるいは（±）−ｃ
ｉｓ酸）を光学分割でき、しかも同時に分割剤として用
いた（±）−ｅｉｓ酸（あるいは（±）−ＥＢＡ）も同
時に光学分割されて、分割剤として用いた以上の量の光
学活性なｃｉｓ酸（またはＥＢＡ）を回収できるという
同時相互光学分割が可能である。本発明でＥＢＡとｃｉ
ｓ酸を含有する溶液を調製するためには、水、メタノー
ル、エタノール、１−プロパツール、２−プロパツール
、アセトン、エチルメチルケトン等の溶媒を単独あるい
は混合して用いることができるが、適当な溶解度をもち
、且つ安価な溶媒である水、メタノール、２−プロパツ
ールを用いるのが特に好ましい。また、（＋）−ＥＢＡ
・（−）−ｅｉｓ酸塩あるいは（−）−ＥＢＡ ・（＋
）−ｅｉｓ酸塩を晶出させる時、溶液中で（±）−Ｅ
ＢＡと（±）−ｅｉｓ酸のみが等モル量ある場合には、
種結晶を接種することが必要であるが、ＥＢＡとｅｉｓ
酸の光学活性体のうち、少なくとも１種の濃度が高い場
合には、必ずしも種結晶の接種は必要ではない。しかし
一般に接種した方が効率良く高光学純度の難溶性ジアス
テレオマー塩が得られるので好ましい。又、追加する（
±）−ＥＢＡおよび（±）−ｅｉｓ酸は、そのまま等モ
ルずつ加えてもよいか、（±）−ＥＢＡ・（±）−ｃｉ
ｓ酸塩の形で追加しても良い。この様にして得られた（
＋）−ＥＢＡ・（−）−ｃｉｓ酸塩あるいは（−）−Ｅ
ＢＡ−（＋）−ｃｉｓ酸塩は、必要あらばこれを再結晶
したのち、水溶性の塩基で処理し、遊離したアミンを有
機溶媒で抽出した後、蕉留して（＋）−ＥＢＡあるいは
（−）−ＥＢＡを得る。In carrying out the present invention, (±)-EBA at 4t
and (±)-cis acid, (+)-
EBA -(-)-cis acid salt or (-)-EBA
Although it is possible to apply a simple alternating first crystallization method in which seed crystals of -(+)-cis salts are inoculated, in addition,
For example, (±)-EBA (or (±)-cis acid)
When resolving (±)-EBA (or (±)-c
is acid), and at the same time, the (±)-eis acid (or (±)-EBA) used as the resolving agent was also optically resolved, resulting in an optically active cis acid in an amount greater than that used as the resolving agent. Simultaneous mutual optical separation is possible in which (or EBA) can be recovered. In the present invention, EBA and ci
In order to prepare a solution containing s-acid, solvents such as water, methanol, ethanol, 1-propanol, 2-propanol, acetone, and ethyl methyl ketone can be used alone or in combination. It is particularly preferable to use water, methanol, and 2-propanol, which are solvents that have a high solubility and are inexpensive. Also, (+)-EBA
・(-)-eis acid salt or (-)-EBA ・(+
)-Eis salt in solution, (±)-E
When only BA and (±)-eis acid are present in equimolar amounts,
Although it is necessary to inoculate seed crystals, EBA and EIS
When the concentration of at least one of the optically active acids is high, inoculation of seed crystals is not necessarily necessary. However, inoculation is generally preferable because it allows a highly optically pure, poorly soluble diastereomeric salt to be obtained more efficiently. Also, add (
±)-EBA and (±)-eis acid may be added as is in equimolar amounts, or (±)-EBA・(±)-ci
It may be added in the form of s-acid. Obtained in this way (
+)-EBA・(-)-cis acid salt or (-)-E
After recrystallizing BA-(+)-cis acid salt if necessary, it is treated with a water-soluble base, the liberated amine is extracted with an organic solvent, and then distilled to produce (+)-EBA or (-)-EBA is obtained.
又、水溶液中にアルカリ塩として存在するｃｉｓ酸は、
この水溶液に塩酸、硫酸などの鉱酸を作用させることに
より、（−）−ｅｉｓ酸塩あるいは（＋）−ｅｉｓ酸を
得る事ができる。つぎに実施例をあげて本発明をさらに
具体的に説明する。In addition, cis acid that exists as an alkali salt in an aqueous solution is
By treating this aqueous solution with a mineral acid such as hydrochloric acid or sulfuric acid, a (-)-eis acid salt or a (+)-eis acid can be obtained. Next, the present invention will be explained in more detail with reference to Examples.
実施例１゜
メタノール１０ｍ１に（±）−ＥＢＡ −（±）−ｃｉ
ｓ酸塩２゜６０ｇ（６，８ｍｍｏｌ）を加え加熱し完全
に溶解させた。室温に放置し４０°Ｃまで冷却した所で
（−）−ＥＢＡ・（＋）−ｃｉｓ酸塩の種結晶（［αげ
＋２７．７°（ｃ＝１、メタノール））を１１ｍｇ接種
し、室温（２０°Ｃ）にて１晩放置した後晶出した結晶
をろ別した。−回目の晶出としてＯ，１，５ｇの（−）
−ＥＢＡ（＋ ） −ｅｉｓ酸塩を得た。 ［α］Ｄ＋
２１．９°（ｃ＝１、メタノール）９母液に追加分とし
て（±）−、ＥＢＡ −（±）−ｅｉｓ酸塩０．３１ｇ
を加え加熱して完全に溶解した。室温に放置し、３０°
Ｃまで冷却した後（＋）−ＥＩ３Ａ・ｃ ）−ｃｔｓ
酸ｔＡノ種結晶（［ａｌ ”、’ −２６，４゜（ｃ＝
１、メタノール））を１０ｍｇ接種し１晩放置した。析
出した結晶をろ別し、２回目の晶出として０゜４２ｇの
（＋ ）−ＥＢＡ−（−）−ｅｉｓ酸を得た。 ［Ｑ］
Ｄ−２ｉ、８゜（ｃ＝１、メタノール）以下同様な操
作を繰り返して次のような結果を得た。Example 1゜(±)-EBA-(±)-ci in 10 ml of methanol
2.60 g (6.8 mmol) of s-acid was added and heated to completely dissolve. After being left at room temperature and cooled to 40°C, 11 mg of seed crystals of (-)-EBA/(+)-cis acid salt ([α + 27.7° (c = 1, methanol)) were inoculated, and the temperature was kept at room temperature. After standing overnight at (20°C), the crystals that crystallized were filtered off. - as the second crystallization of O, 1,5 g (-)
-EBA(+)-eis acid salt was obtained. [α]D+
21.9° (c=1, methanol) 9 Addition of (±)-, EBA-(±)-eis acid salt 0.31 g to the mother liquor
was added and heated to completely dissolve. Leave at room temperature, 30°
After cooling to C (+)-EI3A・c)-cts
Acid tA seed crystal ([al ”,' -26,4° (c=
1. 10 mg of methanol) was inoculated and left overnight. The precipitated crystals were filtered to obtain 0.42 g of (+)-EBA-(-)-eis acid as the second crystallization. [Q]
D-2i, 8° (c=1, methanol) and the following similar operations were repeated to obtain the following results.
晶出回数 晶出塩 収量 ［α］ｐ（ｅ＝ １．
メタ／−ル）３回目 （−）−ＥＢＡ＝（＋）−ｅｉｓ
酸 ０．４０ｇ ＋ ２３．８゜４回目 （＋
）−ＥＢＡ−（−）−ｅｉｓ酸 ０．３２ｇ
−２５，２゜以上の操作によって得られた（＋）−ＥＢ
Ａ・（−）−ｃｉｓ酸塩０．７４ｇをメタノール６ｍｌ
から再結晶し、０．３２ｇの精製（＋）−ＥＢＡ・（−
）−ｅｉｓ酸塩を得た。ｍｐ １８２−１８８°Ｃ１［
α１２７ Ｑ８．８°（ｃ＝１、メタノール）。この
精製（＋）ＥＢＡ・（−）−ｃｉｓ酸塩に１規定の水酸
化ナトリウム水溶液０．８ｍｌを加え、エーテル抽出し
、有機層の溶媒を減圧で留去することにより（＋ ）−
ＥＢＡ９４ｍｇを得た。［Ｑ］Ｄ＋６．６°（ｃ＝１゜
、５．９９％エタノール）、光学純度は１００％であっ
た。エーテル抽出後の水層に濃塩酸を加えてボンゴ−レ
ッド酸性とした。Number of crystallizations Crystallized salt Yield [α]p(e=1.
meta/-ru) 3rd time (-)-EBA=(+)-eis
Acid 0.40g + 23.8゜4th time (+
)-EBA-(-)-eis acid 0.32g
(+)-EB obtained by operation at -25.2° or more
A.(-)-cis acid salt 0.74g in methanol 6ml
Recrystallized from 0.32g of purified (+)-EBA・(-
)-eis acid salt was obtained. mp 182-188°C1[
α127 Q8.8° (c=1, methanol). By adding 0.8 ml of 1 N aqueous sodium hydroxide solution to this purified (+)EBA・(-)-cis acid salt, extracting with ether, and distilling off the solvent of the organic layer under reduced pressure, (+)-
94 mg of EBA was obtained. [Q]D+6.6° (c=1°, 5.99% ethanol), optical purity was 100%. After the ether extraction, concentrated hydrochloric acid was added to the aqueous layer to make it Bongo Red acidic.
析出した沈殿をろ別することにより（−）−ｃｉｓ酸０
．２０ｇを得た。ｒｒｘｐ ２０５−２０７°Ｃ１［α
］ｏ −３６，４゜（ｃ＝１．９９％エタノール）、光
学純度は１００％であった。また同様な操作により、粗
（−）−ＥＢＡ・（＋）−ｅｉｓ酸塩０．５５ｇから０
．３５ｇの精製（−）−ＥＢＡ −（＋ ）−ｃｉｓ酸
塩を得た。 ＋２７．４°（ｃ＝１、メタノール）。By filtering the deposited precipitate, (-)-cis acid 0
．． 20g was obtained. rrxp 205-207°C1[α
] o −36.4° (c=1.99% ethanol), and the optical purity was 100%. In addition, by the same operation, from 0.55 g of crude (-)-EBA・(+)-eis acid salt to 0.
．． 35 g of purified (-)-EBA-(+)-cis acid salt was obtained. +27.4° (c=1, methanol).
［Ｃ＋してこれを遊離することにより、（−）−ＥＢＡ
１１６ｍｇ、［ｏ］ ３０−６．５°（Ｃ＝２．９９
％エタノール）光学純度９８％、および０．２２ｇの（
＋）−ｃｉｓ酸、ｍｐ２０２−２０５°Ｃ１［。］”、
、’ ＋３５．６°（ｃ＝ ０．８．９９％エタノール
）、光学純度９８％を得た。[By releasing it by C+, (-)-EBA
116 mg, [o] 30-6.5° (C=2.99
% ethanol) optical purity 98%, and 0.22 g of (
+)-cis acid, mp202-205°C1[. ]”,
,' +35.6° (c = 0.8.99% ethanol), yielding an optical purity of 98%.
（以下空白）(blank below)
Claims (3)
シス−２−ベンズアミドシクロヘキサンカルボン酸の光
学異性体混合物との塩の過飽和溶液に少量の（＋）−α
−エチルベンジルアミン・（−）−シス−２−ベンズア
ミドシクロヘキサンカルボン酸塩又は、（−）−エチル
ベンジルアミン・（＋）−シス−２−ベンズアミドシク
ロヘキサンカルボン酸塩のいずれか一方の難溶性のジア
ステレオマー塩の種晶を接種し、種晶と同種のジアステ
レオマー塩を析出させ、次いで取得したジアステレオマ
ー塩にアルカリ及び酸を作用させて（＋）−α−エチル
ベンジルアミンと（−）−シス−２−ベンズアミドシク
ロヘキサンカルボン酸又は（−）−α−エチルベンジル
アミンと（＋）−シス−２−ベンズアミドシクロヘキサ
ンカルボン酸とを分離することを特徴とする光学分割法
。(1) Add a small amount of (+)-α to a supersaturated solution of a salt of an optical isomer mixture of α-ethylbenzylamine and an optical isomer mixture of cis-2-benzamidocyclohexanecarboxylic acid.
A sparingly soluble dia of either -ethylbenzylamine/(-)-cis-2-benzamide cyclohexanecarboxylate or (-)-ethylbenzylamine/(+)-cis-2-benzamide cyclohexanecarboxylate A seed crystal of a stereomer salt is inoculated to precipitate a diastereomer salt of the same type as the seed crystal, and then the diastereomer salt obtained is treated with an alkali and an acid to form (+)-α-ethylbenzylamine and (- An optical resolution method characterized by separating )-cis-2-benzamidocyclohexanecarboxylic acid or (-)-α-ethylbenzylamine from (+)-cis-2-benzamidocyclohexanecarboxylic acid.
ス−２−ベンズアミドシクロヘキサンカルボン酸塩及び
（−）−α−エチルベンジルアミン・（＋）−シス−２
−ベンズアミドシクロヘキサンカルボン酸塩の接種を交
互に行い、その間に（±）−α−エチルベンジルアミン
及び（±）−シス−２−ベンズアミドシクロヘキサンカ
ルボン酸を溶液に追加して実施する特許請求の範囲第１
項の方法。(2) (+)-α-ethylbenzylamine/(-)-cis-2-benzamide cyclohexanecarboxylate and (-)-α-ethylbenzylamine/(+)-cis-2
- The inoculations of benzamide cyclohexane carboxylic acid salts are carried out alternately, during which time (±)-α-ethylbenzylamine and (±)-cis-2-benzamide cyclohexane carboxylic acid are added to the solution. 1
Section method.
シス−２−ベンズアミドシクロヘキサンカルボン酸を含
有する溶液中に、（＋）−α−エチルベジルアミン、（
−）−α−エチルベンジルアミン、（＋）−シス−２−
ベンズアミドシクロヘキサンカルボン酸又は、（−）−
シス−２−ベンズアミドシクロヘキサンカルボン酸のう
ち少なくとも１種の濃度を高めて実施する特許請求の範
囲第２項の方法。(3) (±)-α-ethylbenzylamine and (±)-
In a solution containing cis-2-benzamidocyclohexanecarboxylic acid, (+)-α-ethyl bezylamine, (
-)-α-ethylbenzylamine, (+)-cis-2-
Benzamidocyclohexanecarboxylic acid or (-)-
The method according to claim 2, which is carried out by increasing the concentration of at least one of cis-2-benzamidocyclohexanecarboxylic acids.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61198134A JP2574254B2 (en) | 1986-08-26 | 1986-08-26 | Optical resolution method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61198134A JP2574254B2 (en) | 1986-08-26 | 1986-08-26 | Optical resolution method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6354341A true JPS6354341A (en) | 1988-03-08 |
| JP2574254B2 JP2574254B2 (en) | 1997-01-22 |
Family
ID=16386014
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61198134A Expired - Lifetime JP2574254B2 (en) | 1986-08-26 | 1986-08-26 | Optical resolution method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2574254B2 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5824545A (en) * | 1981-08-07 | 1983-02-14 | Hiroyuki Nohira | Optical resolution of (+-)-1-(1-naphthyl)ethylamine |
| JPS61134344A (en) * | 1984-12-05 | 1986-06-21 | Nissan Chem Ind Ltd | Optical resolution of (+-)-2-phenylpropionic acid and/or +--2-phenetylamine |
-
1986
- 1986-08-26 JP JP61198134A patent/JP2574254B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5824545A (en) * | 1981-08-07 | 1983-02-14 | Hiroyuki Nohira | Optical resolution of (+-)-1-(1-naphthyl)ethylamine |
| JPS61134344A (en) * | 1984-12-05 | 1986-06-21 | Nissan Chem Ind Ltd | Optical resolution of (+-)-2-phenylpropionic acid and/or +--2-phenetylamine |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2574254B2 (en) | 1997-01-22 |
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