JPS63227543A - Production of optically active 2-(6-methoxy-2-naphthyl) propionic acid - Google Patents
Production of optically active 2-(6-methoxy-2-naphthyl) propionic acidInfo
- Publication number
- JPS63227543A JPS63227543A JP5993387A JP5993387A JPS63227543A JP S63227543 A JPS63227543 A JP S63227543A JP 5993387 A JP5993387 A JP 5993387A JP 5993387 A JP5993387 A JP 5993387A JP S63227543 A JPS63227543 A JP S63227543A
- Authority
- JP
- Japan
- Prior art keywords
- naphthyl
- methoxy
- propionic acid
- optically active
- 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
- CMWTZPSULFXXJA-UHFFFAOYSA-N 2-(6-methoxy-2-naphthalenyl)propanoic acid Chemical compound C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 title claims description 19
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 230000003287 optical effect Effects 0.000 claims abstract description 26
- VKJXAQYPOTYDLO-UHFFFAOYSA-N 4-methylphenethylamine Chemical compound CC1=CC=C(CCN)C=C1 VKJXAQYPOTYDLO-UHFFFAOYSA-N 0.000 claims 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 abstract description 12
- 239000013078 crystal Substances 0.000 abstract description 9
- 239000002904 solvent Substances 0.000 abstract description 8
- UZDDXUMOXKDXNE-UHFFFAOYSA-N 1-(4-methylphenyl)ethanamine Chemical compound CC(N)C1=CC=C(C)C=C1 UZDDXUMOXKDXNE-UHFFFAOYSA-N 0.000 abstract description 7
- 238000009835 boiling Methods 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 4
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 abstract description 4
- 239000012454 non-polar solvent Substances 0.000 abstract description 4
- 239000012299 nitrogen atmosphere Substances 0.000 abstract description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 239000006227 byproduct Substances 0.000 abstract description 2
- 239000011261 inert gas Substances 0.000 abstract description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 20
- 238000000034 method Methods 0.000 description 19
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 13
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 235000019260 propionic acid Nutrition 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- -1 -nonane Chemical compound 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 150000003947 ethylamines Chemical class 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000006340 racemization Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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−（６−メトキシ−２−ナフチル
）プロピオン酸の新規製造法に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel method for producing optically active 2-(6-methoxy-2-naphthyl)propionic acid.
（＋）−２−（６−メトキシ−２−ナフチル）プロピオ
ン酸は、抗炎症、鎮痛および下前作用を有し、医薬品と
して重要な化合物である。(+)-2-(6-Methoxy-2-naphthyl)propionic acid has anti-inflammatory, analgesic, and laxative effects, and is an important compound as a pharmaceutical.
（至）−２−（６−メトキシ−２−ナフチル）プロピオ
ン酸を光学活性１− （ｐ −） ！Ｊル）エチルアミ
ンを用いて光学分割する方法はすでに知られている（特
開昭５９−１５２３４６号）。(to) -2-(6-methoxy-2-naphthyl)propionic acid with optical activity 1-(p-)! A method of optical resolution using ethylamine is already known (Japanese Patent Laid-Open No. 152346/1983).
上記の方法は他の公知方法よりもすぐれているが、光学
分割と同時に光学分割されない対掌体がラセミ化する、
いわゆる同時ラセミ分割法ではないため、目的とする光
学活性体を１００％以上得ることは不可能である。Although the above method is superior to other known methods, the enantiomer that is not optically resolved becomes racemized at the same time as the optical resolution.
Since this is not a so-called simultaneous racemic resolution method, it is impossible to obtain 100% or more of the desired optically active substance.
本発明は、２−（６−メトキシ−２−ナフチル）プロピ
オン酸の光学分割の効率化を図るため、光学活性体を１
００％以上の収率で得られるいわゆる同時ラセミ分割法
を提供するものである。In order to improve the efficiency of optical resolution of 2-(6-methoxy-2-naphthyl)propionic acid, the present invention aims to improve the efficiency of optical resolution of 2-(6-methoxy-2-naphthyl)propionic acid.
This invention provides a so-called simultaneous racemic resolution method that can be obtained with a yield of 0.00% or more.
本発明は、沸点１２０℃以上の無極性溶媒中でロー２−
（６−メトキシ−２−ナフチル）プロピオン酸を、光学
活性１− （ｐ −トリル）工チルアミンを用いて光学
分割することを特徴とする光学活性２−（６−メトキシ
−２−ナフチル）プロピオン酸の製造法に関する。In the present invention, the low 2-
Optically active 2-(6-methoxy-2-naphthyl)propionic acid characterized by optically resolving (6-methoxy-2-naphthyl)propionic acid using optically active 1-(p-tolyl)engineered tylamine. Concerning the manufacturing method.
本発明方法を実施するには、例えば沸点１２０℃以上の
無極性溶媒に（：ｌ：）−２−（６−メトキシ−２−ナ
フチル）プロピオン酸と光学活性１−（ｐ−）リル）エ
チルアミンを添加し、析出した両者のジアステレオマー
塩を懸濁状態で光学分割すればよい。To carry out the method of the present invention, for example, (:l:)-2-(6-methoxy-2-naphthyl)propionic acid and optically active 1-(p-)lyl)ethylamine are added to a nonpolar solvent with a boiling point of 120°C or higher. may be added, and the precipitated diastereomer salts of both may be optically resolved in a suspended state.
本発明に用いる溶媒は、反応に悪影響を及は゛さイ沸点
が少なくとも１２０℃以上で、かつ操作温度で２−（６
−メトキシ−２−ナフチル）プロピオン酸と光学活性な
１−（ｐ−トリル）エチルアミ）５塩が難溶となるもの
から広範囲に選択しうる。この具体例としては沸点が１
２０℃以上の無極性溶媒があげられるが、炭素数８以上
の脂肪族炭化水素が好ましく、例えばｎ−オクタン、ｎ
−ノナン、ｎ−デカン、ｎ−ウンデカン及びデカリン又
はこれらの混合物などが挙げられる。その使用量は分割
するプロピオン酸１ｇに対し、５〜３０ｍ１程度がよい
。The solvent used in the present invention should have a boiling point of at least 120°C or higher without adversely affecting the reaction, and should have a boiling point of at least 2-(6
-Methoxy-2-naphthyl)propionic acid and the optically active 1-(p-tolyl)ethylamide) 5-salt can be selected from a wide range of salts that are sparingly soluble. As a specific example of this, the boiling point is 1
Examples include nonpolar solvents with a temperature of 20°C or higher, but aliphatic hydrocarbons having 8 or more carbon atoms are preferred, such as n-octane, n-octane,
-nonane, n-decane, n-undecane and decalin or mixtures thereof. The amount used is preferably about 5 to 30 ml per 1 g of propionic acid to be divided.
無極性溶媒に極性溶媒を添加することもできるが、この
際に添加する極性溶媒は、数％〜数十％にとどめるべき
で、２−（６−メトキシ−２−ナフチル）プロピオン酸
と光学活性な１−（ｐ−トリル）エチルアミンの塩の大
部分を操作温度で溶解させない添加量が目安となる。It is also possible to add a polar solvent to a non-polar solvent, but the polar solvent added in this case should be limited to a few percent to several tens of percent. A guideline is an amount that does not dissolve most of the 1-(p-tolyl)ethylamine salt at the operating temperature.
Ｃ１：ｌ−２−（６−メトキシ−２−ナフチル）プロピ
オン酸と光学活性１−（ｐ−トリル）エチルアミンとの
使用割合は特に限定されず、前者に対し後者ｏ、７〜２
モルと広範囲に選択しうるが、当モル量使用するのが
分割効率の点から好ましい。ここでｆ十） −１−（ｐ
−１リル）エチルアミンを用いた場合には（＋）−２−
（６−メトキシ−２−ナフチル）プロピオン酸との塩の
結晶が増加し、Ｈ−１−（ｐ−トリル）エチルアミンを
用いた場合にはＨ−２−（６−メトキシ−２−ナフチル
）プロピオン酸との塩の結晶が増加する。C1: The ratio of l-2-(6-methoxy-2-naphthyl)propionic acid and optically active 1-(p-tolyl)ethylamine to be used is not particularly limited;
Although it can be selected from a wide range of moles, it is preferable to use equimolar amounts from the viewpoint of splitting efficiency. where f1) -1-(p
-1lyl) When using ethylamine, (+)-2-
Crystals of the salt with (6-methoxy-2-naphthyl)propionic acid increased, and when H-1-(p-tolyl)ethylamine was used, H-2-(6-methoxy-2-naphthyl)propionic acid Crystals of salts with acids increase.
光学分割は通常１２０℃以上、好ましくは１２０〜１５
０℃で数時町〜７０時間で終了するが、分割温度、溶媒
の種類により変化する。Optical resolution is usually 120°C or higher, preferably 120-15
The process can be completed in a few hours to 70 hours at 0°C, but this will vary depending on the splitting temperature and type of solvent.
また、副生成物の生成を避けるために、分割は不活性気
体、例えば窒素雰囲気中で行うのが望ましい。Furthermore, in order to avoid the formation of by-products, the splitting is preferably carried out in an inert gas atmosphere, such as nitrogen.
分割終了後、結晶を戸数し、得られた光学活性２−（６
−メトキシ−２−ナフチル）プロピオン酸・光学活性１
−（ｐ−）リル）エチルアミン塩を、必要に応じメタノ
ールなどのアルコール等の有機溶媒で再結晶した後、塩
酸、硫酸、硝酸等の鉱酸を作用させて分解し、遊離した
光学活性２−（６−メトキシ−２−ナフチル）プロピオ
ン酸をそのまま戸数し、鉱酸水で洗浄するか、′又はエ
ーテル、クロロホルム等の有機溶媒で抽出することによ
り、純度の高い目的物を得ることができる。After the splitting, the crystals were separated and the obtained optical activity 2-(6
-methoxy-2-naphthyl)propionic acid/optical activity 1
-(p-)lyl)ethylamine salt is recrystallized if necessary in an organic solvent such as an alcohol such as methanol, and then decomposed by the action of a mineral acid such as hydrochloric acid, sulfuric acid, or nitric acid to liberate optically active 2- (6-Methoxy-2-naphthyl)propionic acid is taken as it is and washed with mineral acid water or extracted with an organic solvent such as ether or chloroform to obtain the desired product with high purity.
なお、分割母液は次の分割の際の溶媒として使用するこ
とができる。又、精製工程で生ずる再結晶ろ液から溶媒
を除去して該ろ液中の塩の結晶を得、これをラセミ化す
ることなく、次の分割に使用することができる。Note that the splitting mother liquor can be used as a solvent for the next splitting. Furthermore, the solvent can be removed from the recrystallized filtrate produced in the purification step to obtain salt crystals in the filtrate, which can be used for the next separation without racemization.
本発明方法は、再結晶法による通常の光学分割法とは異
なり、光学分割を結晶が析出した状態でおこなう点で極
めて特異な光学分割方法であり、本発明方法によれば、
光学純度約５０％の粗製光学活性−２−（６−メトキシ
−２−ナフチル）プロピオン酸・光学活性−１−（ｐ−
トリル）エチルアミン塩としたのち、これを再結晶する
ことで所望の光学活性体を得ることができる上、再結晶
ろ液中に含まれる所望でない２−（６−メトキシ−２−
ナフチル）プロピオン酸の対掌体を新たにラセミ化する
ことなく回収し、不足の２−（６−メトキシ−２−ナフ
チル）プロピオン酸・（十）−１−（ｐ−トリル）エチ
ルアミン塩を追加し、再び本発明方法を実施することで
連続的に光学分割することが可能に旋光性を示すプロピ
オン酸のリッチなものを原６一
料としても反対の旋光性を示すプロピオン酸が得られる
ということは驚くべきことである。The method of the present invention is a very unique optical resolution method in that the optical resolution is carried out in a state where crystals are precipitated, unlike ordinary optical resolution methods using recrystallization methods.According to the method of the present invention,
Crude optically active-2-(6-methoxy-2-naphthyl)propionic acid with optical purity of approximately 50%, optically active-1-(p-
By recrystallizing the resulting tolyl)ethylamine salt, the desired optically active substance can be obtained, and the undesired 2-(6-methoxy-2-
The enantiomer of naphthyl)propionic acid is recovered without new racemization, and the missing 2-(6-methoxy-2-naphthyl)propionic acid (decade)-1-(p-tolyl)ethylamine salt is added. However, by carrying out the method of the present invention again, it is possible to carry out continuous optical resolution, and even if a rich propionic acid exhibiting optical rotation is used as a raw material, propionic acid exhibiting the opposite optical rotation can be obtained. That is surprising.
また、本発明による光学活性な１− （ｐ −トリル）
エチルアミンを用いて光学分割と一方の対掌体のラセミ
化とを同時に行う方法によって実施した場合と、比較対
照として光学活性な１− （ｐ −トリル）エチルアミ
ンを用いてジアステレオマー塩を形成させ、生成した２
種類のジアステレオマー塩の溶解度差によって分割を行
った場合（参考側参照）とを表１のごとく比較すると、
本発明方法と対照方法によって得られた２−（６−メト
キシ−２−ナフチル）プロピオン酸の光学純度がほとん
ど同じにもかかわらず、本発明方法では対照方法に対し
て約３０％も収率が向上するといったときわめて大きな
効果も有する。Furthermore, optically active 1-(p-tolyl) according to the present invention
One case was carried out by a method in which optical resolution and racemization of one enantiomer were carried out simultaneously using ethylamine, and the other was carried out by a method in which diastereomeric salts were formed using optically active 1-(p-tolyl)ethylamine as a comparison. , generated 2
Comparing the case where separation is performed based on the solubility difference of different types of diastereomeric salts (see reference side) as shown in Table 1,
Although the optical purity of 2-(6-methoxy-2-naphthyl)propionic acid obtained by the method of the present invention and the control method are almost the same, the yield of the method of the present invention is about 30% higher than that of the control method. It also has a very large effect.
表１
＊ 使用した（至）−２−（６−メトキシ−２−ナフチ
ル）プロピオン酸中の（＋）一体に対する回収された２
−（６−メトキシ−２−ナフチル）プロピオン中の（＋
）一体の収率
〔実施例〕
以下実施例により本発明を具体的に説明する。Table 1 * Recovered 2 relative to (+) unit in (to)-2-(6-methoxy-2-naphthyl)propionic acid used
- (+ in (6-methoxy-2-naphthyl)propion)
) Integral Yield [Example] The present invention will be specifically explained below with reference to Examples.
実施例１゜
（ｄ−２−（６−メ）キシ−２−ナフチル）プロピオン
酸０．８９ ｇ （３，９ｍｍｏｌ）およびｆ＋）−１
−（ｐ−トリル）エチルアミン０．５２ ｇ （３，９
ｍｍｏｌ）にｎ−オクタン１４．１ｍｌを加え、生成し
たジアステレオマー塩の大半が不溶となる状態で、攪拌
しなから浴温１３５℃で６０時間加熱還流した。反応は
窒素雰囲気中で行い、反応終了後にベンゼン２０ｍ１お
よびＩＮ水酸化ナトリウム水溶液７０ｍ１を加え、水層
と有機層を分離した。水層をベンゼン１０ｍ１で３回洗
浄したのち６Ｎ塩酸２０ｒｒ＋ｔを加え酸性としたのち
、クロロホルム２０ｍ１で３回抽出した。抽出液を無水
硫酸ナトリウムで乾燥したのち溶媒留去することで光学
純度５０．７％の（十ｌ−２−（６−メトキシ−２−ナ
フチル）プロピオン酸０．６３ ｇ （２，７ｍｍｏｌ
）（［α］、＋３３．２°（ＣＩ、 ＣＨＣＩｇ））
を得た。用いた（至）−２−（６−メトキシ−２−ナフ
チル）プロピオン酸に含まれる（＋）一体に対する回収
された光学純度５０．７％の２−（６−メトキシ−２−
ナフチル）プロピオン酸中の（＋）一体の収率は１．０
６．５％であった。Example 1゜(d-2-(6-me)xy-2-naphthyl)propionic acid 0.89 g (3,9 mmol) and f+)-1
-(p-tolyl)ethylamine 0.52 g (3,9
14.1 ml of n-octane was added to the mixture (14.1 ml of n-octane), and the mixture was heated under reflux at a bath temperature of 135° C. for 60 hours without stirring, with most of the generated diastereomeric salts insoluble. The reaction was carried out in a nitrogen atmosphere, and after the reaction was completed, 20 ml of benzene and 70 ml of IN sodium hydroxide aqueous solution were added to separate the aqueous layer and the organic layer. The aqueous layer was washed three times with 10 ml of benzene, made acidic by adding 20 ml of 6N hydrochloric acid, and extracted three times with 20 ml of chloroform. After drying the extract over anhydrous sodium sulfate, the solvent was distilled off to obtain 0.63 g (2.7 mmol) of (10l-2-(6-methoxy-2-naphthyl)propionic acid) with an optical purity of 50.7%.
) ([α], +33.2° (CI, CHCIg))
I got it. The recovered optical purity of 2-(6-methoxy-2-2-
The yield of (+) monomer in naphthyl)propionic acid is 1.0
It was 6.5%.
実施例２゜
（ｆｆｌ−２−（６−メトキシ−２−ナフチル）プロピ
オ７ｅ ０．８９ ｇ （３，９ｍｍｏｌ ）および（
＋）−１−（ｐ−トリル）エチルアミン０゜５２ ｇ
（３，９ｍｍｏｌ ）にｎ−オクタン１４．１ ｍｌを
加え、生成したジアステレオマー塩の大半が不溶となる
状態で、窒素雰囲気中、攪拌しなから浴温１３５℃で６
０時間加熱還流した。分割終了後、結晶を加数しく＋ｌ
−２−（６−メトキシ−２−ナフチル）プロピオン酸・
ｆ＋１−１−（ｐ−）リル）エチルアミン塩０．９７６
ｇを得た。この塩０．６７２ｇを９５％エタノール６
．０ｍｌで再結晶して得られた結晶０．４７５ｇのうち
０．３７５ｇを再び９５％エタノール３．６ｍｌで再結
晶することで、（＋）−２−（６−メトキシ−２−ナフ
チル）プロピオン酸・（＋） −１−（ｐ−）リル）エ
チルアミン塩０．３２０ｇ（［α〕４３５ ２．５°（
ＣＩ 、 ＭｅＯＨ） 。Example 2゜(ffl-2-(6-methoxy-2-naphthyl)propio7e 0.89 g (3.9 mmol) and (
+)-1-(p-tolyl)ethylamine 0°52 g
(3.9 mmol) was added with 14.1 ml of n-octane, and in a state in which most of the diastereomer salts formed were insoluble, the mixture was heated to 135°C in a nitrogen atmosphere without stirring.
The mixture was heated under reflux for 0 hours. After dividing, add the crystal to +l
-2-(6-methoxy-2-naphthyl)propionic acid.
f+1-1-(p-)lyl)ethylamine salt 0.976
I got g. Add 0.672g of this salt to 95% ethanol6
．． (+)-2-(6-methoxy-2-naphthyl)propionic acid was obtained by recrystallizing 0.375 g of the 0.475 g of crystals obtained by recrystallizing with 0 ml of 95% ethanol.・(+)-1-(p-)lyl)ethylamine salt 0.320g ([α]435 2.5°(
CI, MeOH).
ｍｐ１７０−１７２°Ｃ）を得た。mp170-172°C) was obtained.
この塩９９．６１１１ｇにＩＮ塩酸２ ｍｌを加えたの
ち結晶を加数しＩＮ塩酸で洗浄後、乾燥し、（＋） −
２−（６−メトキシ−２−ナフチル）プロピオン酸６２
．４ｍｇ（１：α）Ｂ” ＋６５．９°（ＣＩ、ＣＨＣ
Ｉｇ）、 １５７．５〜１５８．０℃）を得た。After adding 2 ml of IN hydrochloric acid to 99.6111 g of this salt, the crystals were added, washed with IN hydrochloric acid, dried, and (+) -
2-(6-methoxy-2-naphthyl)propionic acid 62
．． 4mg (1:α)B” +65.9° (CI, CHC
Ig), 157.5-158.0°C) was obtained.
実施例３゜
実施例２と同様にして光学純度５１％の（＋）−２−（
６−メトキシ−２−ナフチル）プロピオン酸・（＋）
−１−（ｐ−１リル）エチルアミン塩を再結−１〇−
晶した時の再結晶ろ液の溶媒を留去する“ことで、光学
純度約２０％の（→−２−（６−メトキシ−２−ナフチ
ル）フ゛ロピオン酸・（十）−１−（ｐ−トリル）エチ
ルアミン塩０．２６２ｇを得た。この塩に（至）−２−
（６−メトキシ−２−ナフチル）プロピオン酸０．７２
３ｇ及びｆ＋）−１−（ｐ−）リル）エチルアミン０．
４２５ｇを追加し、実施例１と同様に操作することで光
学純度４９．８％のｆ十） −２−（６−メトキシ−２
−ナフチル）プロピオン酸０．６４ ｇ （２，８ｍｍ
ｏｌ ）（［α）、＋３２．６°（Ｃ１，ＣＨＣｌ３）
’）を得た。Example 3゜(+)-2-( with an optical purity of 51%) was prepared in the same manner as in Example 2.
6-methoxy-2-naphthyl)propionic acid (+)
-1-(p-1lyl)ethylamine salt is recrystallized -10- By "distilling off the solvent of the recrystallized filtrate after crystallization," the optical purity of (→-2-(6- 0.262 g of methoxy-2-naphthyl)propionic acid (10)-1-(p-tolyl)ethylamine salt was obtained.
(6-methoxy-2-naphthyl)propionic acid 0.72
3g and f+)-1-(p-)lyl)ethylamine 0.
By adding 425 g and operating in the same manner as in Example 1, f1)-2-(6-methoxy-2
-naphthyl)propionic acid 0.64 g (2,8 mm
ol ) ([α), +32.6° (C1, CHCl3)
') got.
実施例４゜
（＋）−１−（ｐ−）リル）エチルアミンの代りにＨ−
１−（ｐ−）１ｊル）エチルアミンを用い、実施例１と
同様に操作することで光学純度５０，９％（〔α］Ｄ−
３３，３°（ＣＩ、 ＣＨＣｌ３）のｆ−）−２−（６
−メトキシ−２−ナフチル）プロピオン酸を得た。Example 4 H- in place of (+)-1-(p-)lyl)ethylamine
The optical purity was 50.9% ([α]D-
f-)-2-(6 of 33,3°(CI, CHCl3)
-methoxy-2-naphthyl)propionic acid was obtained.
参考例（特開昭５９−１５２３４６号）ロー２−（６−
メトキシ−２−ナフチル）フロピオン＃０．９３ｇおよ
び（＋）−１−（ｐ−１リル）エチルアミン０．５５ｇ
を９５％エタノール１８．Ｏｍｌに加熱溶解し、室温で
放置後に析出した結晶を９５％エタノール２ ｍｌで洗
浄し、乾燥することで（十）−２−（６−メトキシ−２
−ナフチル）プロピオン酸・ｆ＋）−１−（１）−トリ
ル）エチルアミン塩０．７７ｇを得た。この塩の一部分
を塩酸で酸性とし、エーテルで抽出することで得られた
２−（６−メトキシ−２−ナフチル）プロピオン酸は光
学純度４８６４％（〔α〕。＋３１．７°（ＣＩ、 Ｃ
ＨＣｌ３））であった。用いた（至）−２−（６−メト
キシ−２−ナフチル）プロピオン酸に含まれる（＋）一
体に対する回収された塩に含まれる（＋ｌ−２−（６−
メトキシ−２−ナフチル）プロピオン酸の収率は７７．
３％であった。Reference example (Unexamined Japanese Patent Publication No. 59-152346) Row 2-(6-
Methoxy-2-naphthyl) fropion #0.93g and (+)-1-(p-1lyl)ethylamine 0.55g
95% ethanol18. (10)-2-(6-methoxy-2
0.77 g of -naphthyl)propionic acid/f+)-1-(1)-tolyl)ethylamine salt was obtained. 2-(6-methoxy-2-naphthyl)propionic acid obtained by acidifying a part of this salt with hydrochloric acid and extracting with ether has an optical purity of 4864% ([α]. +31.7° (CI, C
HCl3)). The recovered salt contained in the (+l-2-(6-)
The yield of methoxy-2-naphthyl)propionic acid was 77.
It was 3%.
Claims (1)
メトキシ−２−ナフチル）プロピオン酸を、光学活性１
−（ｐ−トリル）エチルアミンを用いて光学分割するこ
とを特徴とする光学活性２−（６−メトキシ−２−ナフ
チル）プロピオン酸の製造法(±)-2-(6-
Methoxy-2-naphthyl)propionic acid with optical activity of 1
- A method for producing optically active 2-(6-methoxy-2-naphthyl)propionic acid, characterized by optical resolution using (p-tolyl)ethylamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5993387A JPS63227543A (en) | 1987-03-17 | 1987-03-17 | Production of optically active 2-(6-methoxy-2-naphthyl) propionic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5993387A JPS63227543A (en) | 1987-03-17 | 1987-03-17 | Production of optically active 2-(6-methoxy-2-naphthyl) propionic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63227543A true JPS63227543A (en) | 1988-09-21 |
Family
ID=13127425
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5993387A Pending JPS63227543A (en) | 1987-03-17 | 1987-03-17 | Production of optically active 2-(6-methoxy-2-naphthyl) propionic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63227543A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5278334A (en) * | 1992-10-01 | 1994-01-11 | Ethyl Corporation | Racemization process |
| US5321154A (en) * | 1991-08-23 | 1994-06-14 | Nagase & Company, Ltd. | Optical resolution of (±)-2-(4-isobutylphenyl)-propionic acid |
-
1987
- 1987-03-17 JP JP5993387A patent/JPS63227543A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5321154A (en) * | 1991-08-23 | 1994-06-14 | Nagase & Company, Ltd. | Optical resolution of (±)-2-(4-isobutylphenyl)-propionic acid |
| US5278334A (en) * | 1992-10-01 | 1994-01-11 | Ethyl Corporation | Racemization process |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0672030B1 (en) | Process for preparing substantially pure enantiomers of phenylpropionic acids | |
| JPH08503949A (en) | Selective crystallization of α-aryl carboxylates | |
| ZA200601262B (en) | Cycloakylaminoacid compounds, processes for making and uses thereof | |
| JPS63227543A (en) | Production of optically active 2-(6-methoxy-2-naphthyl) propionic acid | |
| WO2005121117A1 (en) | Processes for production of optically active compounds | |
| JPS6383056A (en) | Split of diastereomer | |
| JPS61129142A (en) | Separation of p-xylene | |
| JP4380325B2 (en) | Process for producing optically active carboxylic acid | |
| JP3694923B2 (en) | Process for producing optically active 1- (2,4-dichlorophenyl) ethylamine | |
| EP0288647B1 (en) | Derivatives of 5-[2-(1-pyrrolidinyl)ethoxy]-p-cymene, process for their preparation, and medicaments containing these derivatives | |
| JP3738470B2 (en) | Process for producing optically active 1- (dichloro-substituted phenyl) ethylamines | |
| JP2551216B2 (en) | Process for producing optically active 1- (p-chlorophenyl) -1- (2-pyridyl) -3-dimethylaminopropane | |
| KR920005828B1 (en) | Process for preparing salt of 2-(2-aminomethyl)-thiomethyl-5-dimethyl amino methylfuran | |
| JP2819800B2 (en) | Method for producing optically active 1- (p-chlorophenyl) -1- (2-pyridyl) -3-dimethylaminopropane | |
| JP2616211B2 (en) | Preparation of optically active 1,2-propanediamine | |
| JPS625140B2 (en) | ||
| US2118054A (en) | Optical isomers of acyl-beta-alkyl choline salts and intermediates and processes for their production | |
| JPH06107604A (en) | Production of optically active 1-@(3754/24)4-halogenophenyl) ethylamine | |
| JPS60228442A (en) | Production of optically active 2-(6-methoxy-2-naphthyl) propionic acid | |
| JP3284605B2 (en) | Method for producing optically active 1- (1-naphthyl) ethylamine | |
| JPH0813793B2 (en) | Tartaric acid amide derivative | |
| JPS5811851B2 (en) | DL- Efuedrin Okogaku Katsuseitaini Bunkatsusurhouhou | |
| KR20030008708A (en) | Method of preparing optically active mandelic acid | |
| BE876900A (en) | PROCESS FOR THE PRODUCTION OF PYRROLIDINE-2-ONES FROM 3-PYRROLINE-2-ONES AND FOR THE PRODUCTION OF 3-PYRROLINE-2-ONES | |
| JPH0418058A (en) | Method for optically resolving (+-)-1-methyl-2-(4-chlorophenyl)ethylamine |