JPH01216983A - Method for optical resolution of (+-)-tetrahydrofuran-2-carboxylic acid - Google Patents
Method for optical resolution of (+-)-tetrahydrofuran-2-carboxylic acidInfo
- Publication number
- JPH01216983A JPH01216983A JP4195988A JP4195988A JPH01216983A JP H01216983 A JPH01216983 A JP H01216983A JP 4195988 A JP4195988 A JP 4195988A JP 4195988 A JP4195988 A JP 4195988A JP H01216983 A JPH01216983 A JP H01216983A
- Authority
- JP
- Japan
- Prior art keywords
- carboxylic acid
- tetrahydrofuran
- optically active
- salt
- ethylamine
- 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.)
- Pending
Links
- 230000003287 optical effect Effects 0.000 title claims abstract description 15
- UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title claims description 15
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000000126 substance Substances 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 2
- 229910052801 chlorine Inorganic materials 0.000 claims abstract 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 2
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 150000003839 salts Chemical class 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000012281 transfemoral cerebral angiography Methods 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UJJLJRQIPMGXEZ-BYPYZUCNSA-N (2s)-oxolane-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCO1 UJJLJRQIPMGXEZ-BYPYZUCNSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- SOZMSEPDYJGBEK-UHFFFAOYSA-N 1-(4-bromophenyl)ethanamine Chemical compound CC(N)C1=CC=C(Br)C=C1 SOZMSEPDYJGBEK-UHFFFAOYSA-N 0.000 description 1
- PINPOEWMCLFRRB-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanamine Chemical compound CC(N)C1=CC=C(Cl)C=C1 PINPOEWMCLFRRB-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 101100098918 Arabidopsis thaliana TFCA gene Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000003947 ethylamines Chemical class 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Furan Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、下記構造式をもつ化合物（±）−テトラヒド
ロフラン−２−カルボン酸の光学分割方法に関するもの
である。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for optical resolution of a compound (±)-tetrahydrofuran-2-carboxylic acid having the following structural formula.
本発明の方法で得られる光学活性なテトラヒドロフラン
−２−カルボン酸は、グラム陽性菌およびグラム陰性菌
等の感染症の治療に極めて顕著な効果を有するベネム系
抗生物質の原料として重要な化合物゛である。The optically active tetrahydrofuran-2-carboxylic acid obtained by the method of the present invention is an important compound as a raw material for venem antibiotics, which have extremely significant effects on the treatment of infections caused by Gram-positive bacteria and Gram-negative bacteria. be.
〈従来の技術〉
光学活性なテトラヒドロフラン−２−カルボン酸を得る
方法としては、たとえば、分割剤としてブルシンニ水和
物を作用させる光学分割方法（Ｐ。<Prior Art> As a method for obtaining optically active tetrahydrofuran-2-carboxylic acid, for example, an optical resolution method (P.
Ｃ，Ｂｅｌａｎｇｅｒ ａｎｄ Ｈ，讐、Ｒ，Ｖｉｌｌ
ｉａｍｓ、カナデイアン・ジャーナル・オブ・ケミスト
リー（ＣａｎａｄｉａｎＪｏｕｒｎａｌ ｏｆ Ｃｈｅ
ｍｉｓｔｒｙ）、 ６１巻、第１３８３頁（１９８３）
）および分割剤としてキニーネを作用させる光学分割方
法（０，Ｃｅｒｖｉｎｋａら、コレクションΦチェコス
ロバク・ケミカル・コミユニケイジョン（Ｃｏ１−１ｅ
ｃｔｉｏｎ Ｃｚｅｃｈｏ−ｓｌｏｖａｋ Ｃｈｅｍｉ
ｃａｌ ＣｏｍＩＩｕｎｉｃａｔｉｏｎ）、 Ｓｔ巻、
第４０４頁（１９８６））が知られている。C, Belanger and H, enemy, R, Vill
iams, Canadian Journal of Chemistry
mistry), vol. 61, p. 1383 (1983)
) and an optical resolution method in which quinine acts as a resolving agent (0, Cervinka et al., Collection Φ Czechoslovak Chemical Community (Co1-1e
ction Czecho-slovak Chemi
cal ComIIunication), Volume St,
No. 404 (1986)) is known.
〈発明が解決しようとする問題点〉
しかしながら、上記方法により純粋な光学活性体を得る
ためには何回かの再結晶を繰り返す必要があること、ま
た、ここで用いているブルシンまたはキニーネ等の塩基
性天然分割剤は、アルカリ土類金属し極めて毒性が強く
、また高価であり、さらに、天然型光学異性体のみが入
手可能であることから、高光学純度で得られるのは一方
の対掌体のみであるなと、必ずしも良い分割方法とはい
えなかフた。<Problems to be solved by the invention> However, in order to obtain a pure optically active substance by the above method, it is necessary to repeat recrystallization several times. Basic natural resolving agents are alkaline earth metals, which are extremely toxic and expensive, and because only natural optical isomers are available, only one enantiomer can be obtained with high optical purity. It's not necessarily a good way to divide the parts, as it's just the body.
本発明の目的は、上記の問題点を改善し、純粋な光学活
性テトラヒドロフラン−２−カルボン酸を効率的に得る
方法を提供することにある。An object of the present invention is to improve the above problems and provide a method for efficiently obtaining pure optically active tetrahydrofuran-2-carboxylic acid.
〈問題点を解決するための手段〉
本発明者等は、（±）−テトラヒドロフラン−２−カル
ボン酸に対し種々の光学活性なアミンを作用させ、ジア
ステレオマー法による光学分割について鋭意検討したと
ころ、光学活性な１−（４−ハロゲノフェニル）エチル
アミンを作用させることにより光学活性なテトラヒドロ
フラン−２−カルボン酸を高収率かつ高純度で容易に光
学分割できることを見出した。<Means for Solving the Problems> The present inventors have conducted extensive studies on optical resolution using the diastereomer method by reacting various optically active amines with (±)-tetrahydrofuran-2-carboxylic acid. It has been discovered that optically active tetrahydrofuran-2-carboxylic acid can be easily optically resolved in high yield and purity by the action of optically active 1-(4-halogenophenyl)ethylamine.
すなわち、本発明は、（±）−テトラヒドロフラン−２
−カルボン酸に光学活性な１−（４−ハロゲノフェニル
）エチルアミンを作用させることを特徴とする（±）−
テトラヒドロフラン−２−カルボン酸の光学分割方法に
関するものである。That is, the present invention provides (±)-tetrahydrofuran-2
-Characterized by allowing optically active 1-(4-halogenophenyl)ethylamine to act on carboxylic acid (±)-
The present invention relates to a method for optical resolution of tetrahydrofuran-2-carboxylic acid.
以下、本発明の実施態様を順を追フて説明する。Hereinafter, embodiments of the present invention will be explained in order.
適当な溶媒中で（±）−テトラヒドロフラン−２−カル
ボン酸に光学活性な１−（４−ハロゲノフェニル）エチ
ルアミンを作用させ、必要により加熱し溶解させる。Optically active 1-(4-halogenophenyl)ethylamine is allowed to act on (±)-tetrahydrofuran-2-carboxylic acid in a suitable solvent, and if necessary, the mixture is heated and dissolved.
ここで用いられる溶媒としては、水、またはメタノール
、エタノール、１−プロパツール、２−プロパツール、
１−ブタノール、あるいは２−ブタノールなどのアルコ
ール類、またはアセトン、メチルエチルケトンなどのケ
トン類、または酢酸メチル、あるいは酢酸エチルなどの
エステル類、またはベンゼン、トルエン、あるいはキシ
レンなどの芳香族炭化水素類、または塩化メチレン、ク
ロロホルムあるいは四塩化炭素などのハロゲン化炭素類
、またはペンタン、ヘキサン、あるいはシクロヘキサン
などの飽和脂肪族炭化水素類などが好適な例として挙げ
ることができる。これらの溶媒は、単独で使用してもよ
いが、必要に応じて適当な比率で二種またはそれ以上を
混合して使用してもよい。The solvent used here includes water, methanol, ethanol, 1-propanol, 2-propanol,
Alcohols such as 1-butanol or 2-butanol, or ketones such as acetone or methyl ethyl ketone, or esters such as methyl acetate or ethyl acetate, or aromatic hydrocarbons such as benzene, toluene, or xylene, or Preferred examples include halogenated carbons such as methylene chloride, chloroform, and carbon tetrachloride, and saturated aliphatic hydrocarbons such as pentane, hexane, and cyclohexane. These solvents may be used alone, or may be used as a mixture of two or more in an appropriate ratio, if necessary.
ここで用いられる光学活性な１−（４−ハロゲノフェニ
ル）エチルアミンの量は、特に限定されるものではない
が、（±）−テトラヒドロフラン−２−カルボン酸に対
し、０．５から１．１倍モル量が好適である。The amount of optically active 1-(4-halogenophenyl)ethylamine used here is not particularly limited, but is 0.5 to 1.1 times the amount of (±)-tetrahydrofuran-2-carboxylic acid. Molar amounts are preferred.
このようにして得られた過飽和溶液を濃縮および／また
は徐冷して難溶性ジアステレオマー塩を析出させる。こ
の際上記過飽和溶液に難溶性塩である（＋）−テトラヒ
ドロフラン−２−カルボン酸・（−） −１−（４−ハ
ロゲノフェニル）エチルアミン塩または（−）−テトラ
ヒドロフラン−２−カルボン酸・（＋）−１−（４−ハ
ロゲノフェニル）エチルアミン塩を少量接種して析出さ
せてもよい。The supersaturated solution thus obtained is concentrated and/or slowly cooled to precipitate the sparingly soluble diastereomeric salt. At this time, (+)-tetrahydrofuran-2-carboxylic acid/(-)-1-(4-halogenophenyl)ethylamine salt or (-)-tetrahydrofuran-2-carboxylic acid/(+ )-1-(4-halogenophenyl)ethylamine salt may be inoculated in a small amount for precipitation.
難溶性ジアステレオマー塩を溶媒から析出させるための
温度条件としては、上記の各溶媒の凝固点から沸点まで
使用できるが、実際上操作し易い好ましい温度範囲は室
温から液体溶媒の沸点以下である０通常は光学分割剤を
作用させる際に加熱溶解し、得られた溶液を室温まで徐
冷することにより、難溶性ジアステレオマー塩を析出さ
せる方法が好ましく用いられる。The temperature conditions for precipitating the poorly soluble diastereomer salt from the solvent can range from the freezing point to the boiling point of each of the above solvents, but the preferred temperature range for practical ease of operation is from room temperature to below the boiling point of the liquid solvent. Usually, a method is preferably used in which a sparingly soluble diastereomeric salt is precipitated by heating and dissolving it when an optical resolution agent is applied and slowly cooling the resulting solution to room temperature.
かくして得られた難溶性ジアステレオマー塩の結晶は、
ろ過、遠心分離などの通常の固液分離法によって容易に
分離することができる。また、得られた難溶性ジアステ
レオマー塩の結晶は、必要に応じて再結晶してその純度
を高めることができる。The crystals of the poorly soluble diastereomeric salt thus obtained are
It can be easily separated by ordinary solid-liquid separation methods such as filtration and centrifugation. Further, the obtained crystals of the poorly soluble diastereomeric salt can be recrystallized to improve its purity, if necessary.
分離された難溶性ジアステレオマー塩は、公知のいかな
る方法によって分解してもよく、好ましい分解法として
は、たとえば、分離された難溶性ジアステレオマー塩を
水酸化ナトリウム、水酸化カリウムなどの水溶性の塩基
で処理し、遊離したアミンをベンセン、エーテルなどの
有機溶媒で抽出して回収した後、水層に塩酸、硫酸など
の鉱酸を作用させて遊離したカルボン酸をベンゼン、エ
ーテルなどの有機溶媒で抽出し蒸留する方法が挙げられ
る。かくして光学活性な（＋）または（−）−テトラヒ
ドロフラン−２−カルボン酸を得ることができる。The separated sparingly soluble diastereomer salt may be decomposed by any known method, and a preferred method of decomposition is, for example, by decomposing the separated sparingly soluble diastereomer salt in an aqueous solution such as sodium hydroxide or potassium hydroxide. After treatment with an aqueous base and recovering the liberated amine by extracting it with an organic solvent such as benzene or ether, the aqueous layer is treated with a mineral acid such as hydrochloric acid or sulfuric acid, and the liberated carboxylic acid is extracted with an organic solvent such as benzene or ether. Examples include a method of extraction with an organic solvent and distillation. In this way, optically active (+) or (-)-tetrahydrofuran-2-carboxylic acid can be obtained.
また有機溶媒で抽出して回収した分割剤の光学活性なア
ミンは、再使用が可能である。Furthermore, the optically active amine of the resolving agent recovered by extraction with an organic solvent can be reused.
〈実施例〉 以下、実施例により本発明を具体的に説明する。<Example> Hereinafter, the present invention will be specifically explained with reference to Examples.
実施例１
アセトン９ｍｌに（±）−テトラヒドロフラン−２−カ
ルボン酸［以下、（±）−ＴＦＣＡと略記する］ ０．
４６４ｇ （４，０ｍｍｏ ｌ）および（＋） −１−
（４−ブロモフェニル）エチルアミン［以下、（＋）−
ＢＰＥＡと略記する１ ０．７２ｇ （３，６ｍｍｏ
ｌ）を加え、加熱溶解した後、室温まで冷却して２時間
放置した。析出した結晶をろ別することにより粗（−）
−ＴＦＣＡ・（＋）−ＢＰＥＡ塩０．９４２ｇ （３，
０ｍｍｏ １）を得た。この塩をアセトン：水＝１０：
１の混合溶媒３．３ｍｌで２回再結晶することにより精
（−）−Ｔ Ｆ ＣＡ・（＋） −ＢＰＥＡ塩０．３６
３ｇ（１，１ｍｍｏｌ）を得た。用いたく±”） −Ｔ
ＦＣＡの全量に対する収率は２７．５％、［α］ 、２
８−８．１″″ （ｃ＝１．０．メタノール）、融点１
６４〜１６７℃であった。Example 1 (±)-Tetrahydrofuran-2-carboxylic acid [hereinafter abbreviated as (±)-TFCA] was added to 9 ml of acetone.
464g (4,0mmol) and (+) -1-
(4-Bromophenyl)ethylamine [hereinafter referred to as (+)-
BPEA abbreviated as 1 0.72g (3.6mmo
1) was added and dissolved by heating, then cooled to room temperature and left for 2 hours. By filtering the precipitated crystals, coarse (-)
-TFCA・(+)-BPEA salt 0.942g (3,
0 mmo 1) was obtained. Add this salt to acetone: water = 10:
By recrystallizing twice with 3.3 ml of mixed solvent of 1, the purified (-)-T F CA・(+)-BPEA salt 0.36
3 g (1.1 mmol) was obtained. I want to use ±”) -T
The yield based on the total amount of FCA was 27.5%, [α], 2
8-8.1″″ (c=1.0.methanol), melting point 1
The temperature was 64-167°C.
この塩に１規定の水酸化ナトリウム水溶液１゜５ｍｌを
加え、遊離した（＋）−ＢＰＥＡをエーテルで抽出除去
した後、水層にｌ規定の塩酸１゜７ｍｌを加えてエーテ
ルで抽出した。エーテル層を乾燥後、減圧下に溶媒を留
去することにより、（−）−ＴＦＣＡｏ、１２８ｇ （
１，１ｍｍｏ ｌ）を得た。［α コ ｏ２９− ３
０ 、 ２ ” （ｃ＝１．０．り０ロネルム
）、光学純度９９％（文献値＝［α］ｏ＋３０．４゜（
ｃ＝１．０．クロロホルム）、 Ｐ、Ｃ，Ｂｅｌａｎ
ｇｅｒ ａｎｄ Ｈ，Ｗ、Ｒ。To this salt was added 1.5 ml of 1N aqueous sodium hydroxide solution, and the liberated (+)-BPEA was extracted and removed with ether. To the aqueous layer was added 1.7 ml of 1N hydrochloric acid and extracted with ether. After drying the ether layer, the solvent was distilled off under reduced pressure to obtain 128 g of (-)-TFCAo (
1.1 mmol) was obtained. [α Ko o29-3
0, 2'' (c=1.0.0 ronelm), optical purity 99% (literature value = [α] o + 30.4° (
c=1.0. chloroform), P.C.Belan
ger and H,W,R.
Ｗｉｌｌｉａｓｓ、カナデイアン・ジャーナルｅオブ・
ケミストリー（Ｃａｎａｄｉａｎ Ｊｏｕｒｎａｌ ｏ
ｆ Ｃｈｅｍｉｓｔｒｙ）＋、 ６１巻、第１３８３頁
（１９８３）による）であった。Williams, Canadian Journal e of
Chemistry (Canadian Journal o
f Chemistry) +, Vol. 61, p. 1383 (1983)).
実施例２
アセトン１０ｍ１に（±）−ＴＦＣＡｏ、２３２ｇ （
２，０ｍｍｏ ｌ）およびＣ−）−ＢＰＥＡＯ，３６０
ｇ （１，８ｍｍｏ Ｉ）を加え、加熱溶解した。室温
まで冷却して２時間放置した後、析出した結晶をろ別す
ることにより（＋）−ＴＦＣＡ・（−）−ＢＰＥＡ塩０
．２４８ｇ （０，７８ｍｍ０１）を得た。用いた（±
）−ＴＦＣＡの全量に対する収率は３９．０％、［αコ
Ｄ２９＋ ６ 。Example 2 232 g of (±)-TFCAo in 10 ml of acetone (
2,0 mmol) and C-)-BPEAO, 360
g (1.8 mmo I) was added and dissolved by heating. After cooling to room temperature and leaving for 2 hours, the precipitated crystals were filtered to obtain (+)-TFCA/(-)-BPEA salt 0.
．． 248 g (0.78 mm01) were obtained. used (±
) - The yield based on the total amount of TFCA was 39.0%, [αcoD29+ 6 .
０’ （ｃ＝１．０．メタノール）、融点１６３〜１
６７℃であった。0' (c=1.0.methanol), melting point 163-1
The temperature was 67°C.
この塩に１規定の水酸化ナトリウム水溶液】。Add 1N aqueous sodium hydroxide solution to this salt.
３ ｍ ｌを加え、遊離した（−）−ＢＰＥＡをエーテ
ルで抽出除去した後、水層に１規定の塩酸１゜５ｍｌを
加えてエーテルで抽出した。エーテル層を乾燥後、減圧
下に溶媒を留去することにより、（＋）−ＴＦＣＡｏ、
０７８ｇ （０，６６ｍｍ。After adding 3 ml of the mixture and extracting and removing liberated (-)-BPEA with ether, 1.5 ml of 1N hydrochloric acid was added to the aqueous layer and the mixture was extracted with ether. After drying the ether layer, the solvent was distilled off under reduced pressure to obtain (+)-TFCAo,
078g (0,66mm.
１）を得た＊ ＣａＥａ２７＋２５．９° （ｃ＝１
．５．クロ０ネルム）、光学純度８５％であフた。1) was obtained* CaEa27+25.9° (c=1
．． 5. The optical purity was 85%.
実施例３
２−プロパツール４．０ｍｌに（±）−ＴＦＣＡｏ、４
６４ｇ （４，０ｍｍｏ １）および（−）−１−（４
−クロロフェニル）エチルアミン［以下、（−）−ＣＰ
ＥＡと略記する１ ０．４９８ｇ （３゜２ｍｍｏｌ）
を加え、加熱溶解した後、室温まで冷却して３時間放置
した。析出した結晶をろ別することにより粗（＋）−Ｔ
ＦＣＡ・（−） −ＣＰＥＡ塩０．４４１ｇ （１，６
ｍｍｏｌ）を得た。Example 3 2-propatool 4.0ml (±)-TFCAo, 4
64g (4,0mmo 1) and (-)-1-(4
-chlorophenyl)ethylamine [hereinafter, (-)-CP
1 abbreviated as EA 0.498g (3゜2mmol)
was added and heated to dissolve, then cooled to room temperature and left for 3 hours. Crude (+)-T is obtained by filtering the precipitated crystals.
FCA・(-)-CPEA salt 0.441g (1,6
mmol) was obtained.
この塩を２−プロパツール３．０ｍｌで再結晶すること
により精（＋）−ＴＦＣＡ・ （−）−ＣＰＥＡ塩０．
３４０ｇ （１，３ｍｍｏ １）を得た。This salt was recrystallized with 3.0 ml of 2-propanol to obtain 0.0% pure (+)-TFCA/(-)-CPEA salt.
340 g (1,3 mmol 1) were obtained.
用いたく±’）−ＴＦＣＡの全量に対する収率は３２．
５％、［ａｌ ｎ２＠＋ １０ 、６ ” （ｃ＝１
．０． メ９ノール）、融点１５１〜１５４℃であった
。The yield based on the total amount of used ±')-TFCA is 32.
5%, [al n2@+ 10, 6'' (c=1
．． 0. (methanol), and the melting point was 151-154°C.
この塩に１規定の水酸化ナトリウム水溶液１゜６ｍｌを
加え、遊離した（−）−ＣＰＥＡをエーテルで抽出除去
した後、水層に１規定の塩酸１゜７ｍｌを加えてエーテ
ルで抽出した。エーテル層を乾燥後、減圧下に溶媒を留
去することにより、（＋）−ＴＦＣＡｏ、１４３ｇ （
１，２ｍｍｏ ｌ）を得た。 ［α ｌｏ”＋２９．
６ ° （ｃ＝１．０．クロロホルム）、光学純度
９７％であった。To this salt was added 1.6 ml of 1N aqueous sodium hydroxide solution, and the liberated (-)-CPEA was extracted and removed with ether. To the aqueous layer was added 1.7 ml of 1N hydrochloric acid and extracted with ether. After drying the ether layer, the solvent was distilled off under reduced pressure to obtain (+)-TFCAo, 143 g (
1.2 mmol) was obtained. [α lo”+29.
6° (c=1.0.chloroform), and the optical purity was 97%.
実施例４
アセトン：水＝１０：１の混合溶媒２．２ｍｌに（±）
−ＴＦＣＡ ０．４６４ｇ（４，０ｍｍｏ１）および（
＋） −ＣＰＥＡ Ｏ，４７７ｇ （３，１ｍｍｏｌ）
を加え、加熱溶解した後、室温まで冷却して３時間放置
した。析出した結晶をろ別することにより粗（−）−Ｔ
ＦＣＡ・（＋）−ＣＰＥＡ塩０．３７３ｇ （１，４ｍ
ｍｏ １）を得た。この塩を上記の混合溶媒２．２ｍｌ
で再結晶することにより精（−）−ＴＦＣＡ・（＋）
−ＣＰＥＡ塩０．２１９ｇ （０，８１ｍｍｏｌ）を得
た。用いた（±）−ＴＦＣＡの全量に対する収率は２０
．３％、［ａ］ ｏ３’ −１０，８＠（ｃ＝１．０゜
メタノール）、融点１５４〜１５７℃であった。Example 4 Add 2.2 ml of mixed solvent of acetone:water = 10:1 (±)
-TFCA 0.464g (4,0mmol) and (
+) -CPEA O, 477g (3.1 mmol)
was added and heated to dissolve, then cooled to room temperature and left for 3 hours. By filtering the precipitated crystals, crude (-)-T
FCA・(+)-CPEA salt 0.373g (1.4m
mo 1) was obtained. Add this salt to 2.2 ml of the above mixed solvent.
By recrystallizing with
-CPEA salt 0.219g (0.81mmol) was obtained. The yield based on the total amount of (±)-TFCA used was 20
．． 3%, [a]o3'-10,8@(c=1.0° methanol), melting point 154-157°C.
この塩に１規定の水酸化ナトリウム水溶液１゜０ｍｌを
加え、遊離した（＋）−ＣＰＥＡをエーテルで抽出除去
した後、水層に１規定の塩酸ｌ。To this salt was added 1°0 ml of a 1N aqueous sodium hydroxide solution, and the liberated (+)-CPEA was extracted and removed with ether, followed by adding 1N hydrochloric acid (l) to the aqueous layer.
１ｍｌを加丸でエーテルで抽出した。エーテル層を乾燥
後、減圧下に溶媒を留去することにより、（−）−ＴＦ
ＣＡｏ、０８８ｇ （０，７６ｍｍ。1 ml was extracted with ether using Kamaru. After drying the ether layer, the solvent was distilled off under reduced pressure to obtain (-)-TF.
CAo, 088g (0,76mm.
１）を得た。［αコロ２９−２フ、３° （ｃ＝１．０
．りｏ。1) was obtained. [α roller 29-2f, 3° (c=1.0
．． Ri o.
ネルム）、光学純度９０％であった。Nelm), and the optical purity was 90%.
〈発明の効果〉
本発明の方法により光学活性な（＋）および／またはく
−）−テトラヒドロフラン−２−カルボン酸を効率よく
、また高純度で得ることが可能になフた０本発明で分割
剤として用いる光学活性な１−（４−ハロゲノフェニル
）エチルアミンは、４−ハロゲノアセトフェノンの還元
アミノ化により工業的に容易に人手できる（±）−１−
（４−ハロゲノフェニル）エチルアミンを光学分割する
ことにより得られるものであり、毒性も少なく、また両
対掌体が入手可能であることから、分割剤を選ぶことに
より光学活性なく＋）または（−）−テトラヒドロフラ
ン−２−カルボン酸を任意に得ることが可能である。<Effects of the Invention> The method of the present invention makes it possible to efficiently obtain optically active (+) and/or -)-tetrahydrofuran-2-carboxylic acid with high purity. The optically active 1-(4-halogenophenyl)ethylamine used as the agent can be easily obtained industrially by reductive amination of 4-halogenoacetophenone (±)-1-
It is obtained by optically resolving (4-halogenophenyl)ethylamine, has low toxicity, and both enantiomers are available. )-tetrahydrofuran-2-carboxylic acid can optionally be obtained.
特許出願人 野 平 博 之Patent applicant: Hiroyuki Nohira
Claims (1)
［ I ］ ▲数式、化学式、表等があります▼［ I ］ ［式中、Ｘは塩素原子または臭素原子を表し、Ｃ＾＊は
不斉炭素原子を表す。］で表される光学活性な１−（４
−ハロゲノフェニル）エチルアミンを作用させることを
特徴とする（±）−テトラヒドロフラン−２−カルボン
酸の光学分割方法。[Claims] (±)-Tetrahydrofuran-2-carboxylic acid has the general formula [I] ▲ Numerical formulas, chemical formulas, tables, etc.▼ [I] [In the formula, X represents a chlorine atom or a bromine atom, and C ^* represents an asymmetric carbon atom. ] The optically active 1-(4
-A method for optical resolution of (±)-tetrahydrofuran-2-carboxylic acid, which comprises reacting with (halogenophenyl)ethylamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4195988A JPH01216983A (en) | 1988-02-26 | 1988-02-26 | Method for optical resolution of (+-)-tetrahydrofuran-2-carboxylic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4195988A JPH01216983A (en) | 1988-02-26 | 1988-02-26 | Method for optical resolution of (+-)-tetrahydrofuran-2-carboxylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01216983A true JPH01216983A (en) | 1989-08-30 |
Family
ID=12622729
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4195988A Pending JPH01216983A (en) | 1988-02-26 | 1988-02-26 | Method for optical resolution of (+-)-tetrahydrofuran-2-carboxylic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01216983A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4985575A (en) * | 1989-02-07 | 1991-01-15 | Suntory Limited | Process for preparing optically active tetrahydro-2-furoic acid |
| EP0521496A2 (en) * | 1991-07-04 | 1993-01-07 | Consortium für elektrochemische Industrie GmbH | Process for producing optically active carboxylic acids |
| JPH07119222B2 (en) * | 1990-06-29 | 1995-12-20 | アボツト・ラボラトリーズ | R (+)-terazosin |
| US6440721B2 (en) | 2000-06-01 | 2002-08-27 | Sk Corporation | Method for preparing an R- or S-form of α-substituted heterocyclic carboxylic acid and a counter enantiomeric form of α-substituted heterocyclic carboxylic acid ester thereto using enzyme |
| US6455302B1 (en) | 2000-06-01 | 2002-09-24 | Sk Corporation | Method for optically resolving a racemic α-substituted heterocyclic carboxylic acid using enzyme |
| WO2013011999A1 (en) * | 2011-07-20 | 2013-01-24 | 株式会社カネカ | Method for producing optically active 2-methylproline derivative |
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-
1988
- 1988-02-26 JP JP4195988A patent/JPH01216983A/en active Pending
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4985575A (en) * | 1989-02-07 | 1991-01-15 | Suntory Limited | Process for preparing optically active tetrahydro-2-furoic acid |
| JPH07119222B2 (en) * | 1990-06-29 | 1995-12-20 | アボツト・ラボラトリーズ | R (+)-terazosin |
| EP0521496A2 (en) * | 1991-07-04 | 1993-01-07 | Consortium für elektrochemische Industrie GmbH | Process for producing optically active carboxylic acids |
| JPH05213921A (en) * | 1991-07-04 | 1993-08-24 | Consortium Elektrochem Ind Gmbh | Preparation of optically active carboxylic acid, preparation of liquid crystal compound, preparation of high-purity optically active amino acid, and optically active carboxylic acid amide and optically active carboxylic acid |
| US5334730A (en) * | 1991-07-04 | 1994-08-02 | Consortium Fur Elektrochemische Industrie Gmbh | Process for the preparation of optically active carboxylic acids and amide intermediates |
| JP2003534808A (en) * | 2000-06-01 | 2003-11-25 | エスケー コーポレイション | Method for preparing R- or S-form α-substituted heterocyclic carboxylic acid and enantiomer α-substituted heterocyclic carboxylate using an enzyme |
| US6455302B1 (en) | 2000-06-01 | 2002-09-24 | Sk Corporation | Method for optically resolving a racemic α-substituted heterocyclic carboxylic acid using enzyme |
| JP2003534807A (en) * | 2000-06-01 | 2003-11-25 | エスケー コーポレイション | Optical resolution of racemic α-substituted heterocyclic carboxylic acids using enzymes |
| US6440721B2 (en) | 2000-06-01 | 2002-08-27 | Sk Corporation | Method for preparing an R- or S-form of α-substituted heterocyclic carboxylic acid and a counter enantiomeric form of α-substituted heterocyclic carboxylic acid ester thereto using enzyme |
| WO2013011999A1 (en) * | 2011-07-20 | 2013-01-24 | 株式会社カネカ | Method for producing optically active 2-methylproline derivative |
| CN103702981A (en) * | 2011-07-20 | 2014-04-02 | 株式会社钟化 | Method for producing optically active 2-methylproline derivative |
| JPWO2013011999A1 (en) * | 2011-07-20 | 2015-02-23 | 株式会社カネカ | Process for producing optically active 2-methylproline derivative |
| JP2014172820A (en) * | 2013-03-06 | 2014-09-22 | Toray Fine Chemicals Co Ltd | Method for producing optically active tetrahydrofuran-2-carboxylic acid |
| CN104031010A (en) * | 2013-03-08 | 2014-09-10 | 东丽精细化工株式会社 | Manufacturing Method Of Optically Active Tetrahydrofuran-2-carboxylic Acid |
| JP2014172856A (en) * | 2013-03-08 | 2014-09-22 | Toray Fine Chemicals Co Ltd | Method for producing optically active tetrahydrofuran-2-carboxylic acid |
| CN104031010B (en) * | 2013-03-08 | 2017-03-01 | 东丽精细化工株式会社 | The manufacture method of optical activity oxolane -2- formic acid |
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