JP4496585B2 - Process for producing quinolylpropenal - Google Patents
Process for producing quinolylpropenal Download PDFInfo
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- JP4496585B2 JP4496585B2 JP2000014849A JP2000014849A JP4496585B2 JP 4496585 B2 JP4496585 B2 JP 4496585B2 JP 2000014849 A JP2000014849 A JP 2000014849A JP 2000014849 A JP2000014849 A JP 2000014849A JP 4496585 B2 JP4496585 B2 JP 4496585B2
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- BFDPBLWCXIOOLM-HWKANZROSA-N N#C/C=C/c1c(-c(cc2)ccc2F)c(cccc2)c2nc1C1CC1 Chemical compound N#C/C=C/c1c(-c(cc2)ccc2F)c(cccc2)c2nc1C1CC1 BFDPBLWCXIOOLM-HWKANZROSA-N 0.000 description 1
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Description
【０００１】
【発明の属する技術分野】
本発明は、キノリルアクリロニトリル誘導体からキノリルプロペナール誘導体を製造する方法に関する。本発明の製造方法によって得られるキノリルプロペナール誘導体は、例えば、コレステロール低下剤（ＨＭＧ-ＣｏＡ還元酵素阻害薬）の合成中間体として有用な化合物である。
【０００２】
【従来の技術】
従来、キノリルプロペナール誘導体を製造する方法としては、キノリンアクリル酸エステルを水素化ジイソブチルアルミニウムで還元してキノリルプロぺノールを得て、これをオキサリルクロライド及びジメチルスルホキシド、又は二酸化マンガンを用いて酸化してキノリルプロペナールとすることからなる、二工程で製造する方法が知られている（J.Med.Chem.,34,367（1991））。
また、アクリロニトリル化合物の二重結合を保持したまま、シアノ基のみを選択的にホルミル基に還元してプロペナール化合物を製造する方法としては、還元剤として水素化ジイソブチルアルミニウムを用いる方法が知られている（Heterocycles,29,691（1989））。
しかしながら、これらのいずれの方法も、取り扱いや後処理が煩雑となる水素化ジイソブチルアルミニウムや二酸化マンガンを用いなければならず、工業的な製造法としては不利である。
【０００３】
【発明が解決しようとする課題】
本発明の課題は、上記の問題点を解決し、簡便な方法によってキノリルアクリロニトリル誘導体からキノリルプロペナール誘導体を高収率で製造することが出来る、工業的に有利なキノリルプロペナール誘導体の製造方法を提供することにある。
【０００４】
【課題を解決するための手段】
本発明の課題は、式（１）
【０００５】
【化３】
で表わされるキノリルアクリロニトリル誘導体｛３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エンニトリル｝を、ギ酸のアミン塩と有機酸との存在下にて、ラネーニッケルにより還元することを特徴とする、式（２）
【０００７】
【化４】
で表わされるキノリルプロペナール誘導体｛３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エナール｝の製造方法によって解決される。
【０００９】
【発明の実施の形態】
本発明の製造法の出発原料となる式（１）のキノリルアクリロニトリル誘導体は、新規化合物であるが、公知の２−シクロプロピル−４−（４−フルオロフェニル）キノリン−３−カルボアルデヒド（特開平１−２７９８６６号公報、欧州公開特許出願第３０４０６３号公報、米国特許第５０１１９３０号明細書）に、ジエチルシアノメチルホスホネートを、好ましくは水酸化ナトリウムのような塩基と芳香族炭化水素のような溶媒の存在下で反応させることによって製造することができる。
【００１０】
本発明の製造法において利用される還元反応で用いるラネーニッケルとは、ニッケルとアルミニウムとを主成分とする合金であり、ニッケル含有量が、好ましくは１０〜９０重量％、更に好ましくは４０〜８０重量％のものを意味する。通常は、展開されたラネーニッケルが使用されるが、種々の方法によって、前処理されたラネーニッケルや、安定化されたラネーニッケルも使用することが出来る。更に、ラネーニッケル中に、コバルト、鉄、鉛、クロム、チタン、モリブデン、バナジウム、マンガン、スズ、タングステン等のような金属が含まれているものも使用することが出来る。
【００１１】
本発明の製造法の還元反応におけるラネーニッケルの使用量は、原料のキノリルアクリロニトリル誘導体に対して、ニッケル原子換算で、好ましくは０．３０〜２重量倍、更に好ましくは０．４〜１．２重量倍である。
【００１２】
本発明の還元反応において使用するギ酸のアミン塩とは、ギ酸とアミンからなる塩であり、例えば、ギ酸アンモニウム；ギ酸モノメチルアンモニウム、ギ酸モノエチルアンモニウム等のギ酸と一級アミンからなる塩；ギ酸ジメチルアンモニウム、ギ酸ジエチルアンモニウム等のギ酸と二級アミンからなる塩；ギ酸トリメチルアンモニウム、ギ酸トリエチルアンモニウム等のギ酸と三級アミンからなる塩が挙げられるが、好ましくはギ酸アンモニウム、ギ酸トリエチルアンモニウム、更に好ましくはギ酸アンモニウムが使用される。
【００１３】
上記のギ酸のアミン塩の使用量は、原料のキノリルアクリロニトリル誘導体の使用量に対して、好ましくは１．０〜５．０倍モルであり、更に好ましくは１．５〜３．０倍モルである。
【００１４】
本発明の還元反応において使用する有機酸としては、特に炭素数２〜５の低級脂肪酸が好ましく、その例としては、酢酸、プロピオン酸、酪酸、イソ酪酸、吉草酸、イソ吉草酸、ピバル酸が挙げられるが、好ましくは酢酸が使用される。
【００１５】
上記有機酸の使用量は、原料のキノリルアクリロニトリル誘導体に対して、好ましくは３〜５０重量倍、更に好ましくは５〜３０重量倍である。これらの有機酸は、単独又は二種以上を混合して使用しても良い。
【００１６】
本発明の還元反応は、ラネーニッケルの存在下、式（１）のキノリルアクリロニトリル誘導体とギ酸のアミン塩とを有機酸中で接触させることが好ましく、例えば、不活性ガス雰囲気にて、ラネーニッケル、キノリルアクリロニトリル、ギ酸アンモニウム及び有機酸を混合して、加熱攪拌する等の方法によって、常圧下又は加圧下で行われる。その際の反応温度は、好ましくは２０〜１１０℃、更に好ましくは４０〜９０℃である。
【００１７】
また、必要に応じて、無機塩基、有機塩基、白金塩等を系内に添加することによって、反応性を調節しても良い（久保松照夫、小松信一郎、ラネー触媒（川研ファインケミカル株式会社発行）、１２３〜１４７頁に記載）。
【００１８】
なお、最終生成物であるキノリルプロペナール誘導体は、例えば、反応終了後に濾過及び抽出し、蒸留、再結晶、カラムクロマトグラフィー等による一般的な方法によって分離・精製される。
【００１９】
【実施例】
次に、実施例を挙げて本発明を具体的に説明するが、本発明の範囲はこれらに限定されるものではない。
【００２０】
［参考例１］ ３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エンニトリルの合成
攪拌装置、温度計及び滴下漏斗を備えた内容積１００ｍＬのガラス製フラスコに、窒素雰囲気下、２−シクロプロピル−４−（４−フルオロフェニル）キノリン−３−カルボアルデヒド４．９８ｇ（１７．１ミリモル）、純度９８％のジエチルシアノメチルホスホネート３．１０ｍＬ（１８．８ミリモル）、トリカプリルメチルアンモニウムクロライド（Aliquat 336：Aldrich社製）０．１５ｍＬ（０．３３ミリモル）及びトルエン３５ｍＬを加え、液温を２５〜３５℃に保ちながら、２０重量％水酸化ナトリウム水溶液１０．１ｇ（５０．５ミリモル）を５０分間かけてゆるやかに滴下し、同温度で３時間反応させた。その後、純度９８％のジエチルシアノメチルホスホネート０．１４ｍＬ（０．８５ミリモル）を加え、同温度で６６時間反応させた。反応終了後、水５ｍＬを加えて３０分間攪拌した。得られた反応液にトルエン５０ｍＬを加え、有機層を分離して１０重量％水酸化ナトリウム水溶液１０ｍＬで洗浄し、飽和食塩水１０ｍＬを加えた。次いで、１モル／Ｌ塩酸５．６ｍＬを加えて中和した後、有機層を取り出し、攪拌装置を備えた内容積２００ｍＬのガラス製フラスコに移した。それに、無水硫酸ナトリウム１．６０ｇを加えて室温で１時間攪拌させ、更に、活性炭０．１４ｇ（粉末状：和光純薬株式会社製）及びシリカゲル（ワコーゲルＣ−２００：和光純薬株式会社製）０．６２ｇを加えて室温で１．７５時間攪拌させた後、セライトで濾過し、セライトをトルエン５０ｍＬで洗浄した。得られた反応液を減圧下で濃縮すると結晶が析出してきたので、結晶を加熱して溶解させ、次いで、ヘキサン３０ｍＬを加えて３０分間加熱還流させた。その後、液温を５℃まで冷却して２時間攪拌すると結晶が析出してきたので、結晶を濾過した後、ヘキサン３０ｍＬで洗浄し、減圧下、５５℃にて乾燥させて、白色結晶として３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エンニトリル４．８１ｇを得た（収率９０％）。
【００２１】
得られた３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エンニトリルの物性値を次に記す。
融点：１７５〜１７６℃、ＥＩ−ＭＳ（ｍ／ｅ）：３１３（Ｍ−１）、ＣＩ−ＭＳ（ｍ／ｅ）：３１５（Ｍ＋１）
【００２２】
［実施例１］ ３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エナールの製造
攪拌装置、温度計及び滴下漏斗を備えた内容積２００ｍＬのガラス製フラスコに、窒素雰囲気下、参考例１で合成した３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エンニトリル４．０ｇ（１２．７ミリモル）、ギ酸アンモニウム１．６ｇ（２５．４ミリモル）、含水展開ラネーニッケル（川研ファインケミカル（株）製：ＮＤＨＴ−９０：ニッケル含有量５０重量％品）４．４ｇ（ニッケル原子として３７．５ミリモル）及び酢酸４０ｍＬを加え、６５℃で４時間反応させた。反応終了後、室温まで冷却し、エタノール２０ｍＬを加えた後、触媒をセライトで濾過した。次いで、濾液を減圧下で濃縮し、酢酸エチル４０ｍＬを加え、１モル／Ｌ塩酸５ｍＬ、水１０ｍＬ、１モル／Ｌ水酸化ナトリウム水溶液２０ｍＬ、ＤＬ−酒石酸のアルカリ水溶液（ＤＬ−酒石酸１．０ｇを１モル／Ｌ水酸化ナトリウム水溶液１４ｍＬに溶解）１４ｍＬ、飽和食塩水２０ｍＬの順で洗浄した後、有機層を無水硫酸マグネシウムで乾燥した。濾過後、減圧下で濃縮し、薄黄色結晶として純度９８％（高速液体クロマトグラフィーによる面積百分率）の３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エナール３．４ｇを得た（収率８２％）。
【００２３】
３−［２−シクロプロピル−４−（４−フルオロフェニル）−３−キノリル］プロプ−２−エナールの物性値を次に記す。
ＣＩ−ＭＳ（ｍ／ｅ）：３１８（Ｍ＋１）
1Ｈ−ＮＭＲ（ＣＤＣｌ3、δ（ｐｐｍ））：１．０７〜１．１３（２Ｈ，ｍ）、１．４０〜１．４５（２Ｈ，ｍ）、２．３２〜２．３７（１Ｈ，ｍ）、６．４３（１Ｈ，ｄｄ，Ｊ＝７．８，１６．２Ｈｚ）、７．２２〜７．２６（４Ｈ，ｍ）、７．３５〜７．３８（２Ｈ，ｍ）、７．５５（１Ｈ，ｄ，Ｊ＝１６．２Ｈｚ）、７．６４〜７．６９（１Ｈ，ｍ）、７．９７（１Ｈ，ｄ，Ｊ＝８．４Ｈｚ）、９．５１（１Ｈ，ｄ，Ｊ＝７．５Ｈｚ）
【００２４】
【発明の効果】
本発明の製造方法により、簡便な方法によって前記式（１）のキノリルアクリロニトリル誘導体から前記式（２）のキノリルプロペナール誘導体を高収率で製造することが出来る。従って、工業的に有利なキノリルアクロレインの製造法を提供することが出来る。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for producing a quinolylpropenal derivative from a quinolylacrylonitrile derivative. The quinolylpropenal derivative obtained by the production method of the present invention is a useful compound, for example, as a synthetic intermediate for a cholesterol-lowering agent (HMG-CoA reductase inhibitor).
[0002]
[Prior art]
Conventionally, as a method for producing a quinolylpropenal derivative, quinoline acrylate is reduced with diisobutylaluminum hydride to obtain quinolylpropenol, which is oxidized using oxalyl chloride and dimethyl sulfoxide, or manganese dioxide. There is known a method of producing in two steps consisting of quinolylpropenal (J. Med. Chem., 34 , 367 (1991)).
Further, as a method for producing a propenal compound by selectively reducing only a cyano group to a formyl group while retaining the double bond of the acrylonitrile compound, a method using diisobutylaluminum hydride as a reducing agent is known. (Heterocycles, 29 , 691 (1989)).
However, any of these methods must use diisobutylaluminum hydride or manganese dioxide, which is complicated in handling and after-treatment, and is disadvantageous as an industrial production method.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to solve the above-mentioned problems and to produce an industrially advantageous quinolylpropenal derivative capable of producing a quinolylpropenal derivative from a quinolylacrylonitrile derivative in a high yield by a simple method. It is to provide a manufacturing method.
[0004]
[Means for Solving the Problems]
The subject of this invention is Formula (1).
[0005]
[Chemical 3]
In represented by quinolylacrylonitrile derivative {3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] prop-2-ene nitrile}, in the presence of an amine salt with the organic acids formic acid (2), characterized by reduction with Raney nickel
[0007]
[Formula 4]
The quinolylpropenal derivative {3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] prop-2-enal} represented by
[0009]
DETAILED DESCRIPTION OF THE INVENTION
The quinolylacrylonitrile derivative of the formula (1) which is a starting material for the production method of the present invention is a novel compound, but is a known 2-cyclopropyl-4- (4-fluorophenyl) quinoline-3-carbaldehyde (special No. 1-279866, European Published Patent Application No. 304063, US Pat. No. 5,011,930), diethyl cyanomethylphosphonate, preferably a base such as sodium hydroxide and a solvent such as aromatic hydrocarbon. It can manufacture by making it react in presence of.
[0010]
Raney nickel used in the reduction reaction used in the production method of the present invention is an alloy mainly composed of nickel and aluminum, and the nickel content is preferably 10 to 90% by weight, more preferably 40 to 80% by weight. % Means something. Normally, developed Raney nickel is used, but pre-treated Raney nickel or stabilized Raney nickel can also be used by various methods. Furthermore, Raney nickel containing metals such as cobalt, iron, lead, chromium, titanium, molybdenum, vanadium, manganese, tin, tungsten, etc. can be used.
[0011]
The amount of Raney nickel used in the reduction reaction of the production method of the present invention is preferably 0.30 to 2 times by weight, more preferably 0.4 to 1.2, in terms of nickel atoms, relative to the raw material quinolylacrylonitrile derivative. Weight times.
[0012]
The amine salt of formic acid used in the reduction reaction of the present invention is a salt composed of formic acid and an amine, such as ammonium formate; a salt composed of formic acid such as monomethylammonium formate and monoethylammonium formate and a primary amine; dimethylammonium formate. A salt composed of formic acid and a secondary amine such as diethylammonium formate; a salt composed of formic acid and a tertiary amine such as trimethylammonium formate and triethylammonium formate, preferably ammonium formate, triethylammonium formate, more preferably formic acid Ammonium is used.
[0013]
The amount of amine salt of formic acid used is preferably 1.0 to 5.0 times mol, more preferably 1.5 to 3.0 times mol, based on the amount of raw material quinolylacrylonitrile derivative used. It is.
[0014]
The organic acid used in the reduction reaction of the present invention is particularly preferably a lower fatty acid having 2 to 5 carbon atoms. Examples thereof include acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and pivalic acid. Although acetic acid is mentioned, preferably acetic acid is used.
[0015]
The amount of the organic acid used is preferably 3 to 50 times by weight, more preferably 5 to 30 times by weight with respect to the raw material quinolylacrylonitrile derivative. These organic acids may be used alone or in combination of two or more.
[0016]
In the reduction reaction of the present invention, the quinolylacrylonitrile derivative of formula (1) and the amine salt of formic acid are preferably contacted in an organic acid in the presence of Raney nickel. For example, in an inert gas atmosphere, Raney nickel, quino The reaction is carried out under normal pressure or under pressure by a method such as mixing rylacrylonitrile, ammonium formate and an organic acid, and stirring under heating. The reaction temperature in that case becomes like this. Preferably it is 20-110 degreeC, More preferably, it is 40-90 degreeC.
[0017]
If necessary, the reactivity may be adjusted by adding inorganic base, organic base, platinum salt, etc. into the system (Teruo Kubo, Shinichiro Komatsu, Raney Catalyst (published by Kawaken Fine Chemical Co., Ltd.) ), Pages 123-147).
[0018]
The final product, quinolylpropenal derivative, is filtered and extracted after completion of the reaction, and separated and purified by a general method such as distillation, recrystallization, or column chromatography.
[0019]
【Example】
Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.
[0020]
[Reference Example 1] 3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] prop-2-ene nitrile synthesis stirring device, a glass having an inner volume of 100mL equipped with a thermometer and a dropping funnel Under a nitrogen atmosphere, a flask made of 4-cyclopropyl-4- (4-fluorophenyl) quinoline-3- carbaldehyde (4.98 g, 17.1 mmol), 98% pure diethylcyanomethylphosphonate (3.10 mL, 18 0.8 mmol), tricaprylmethylammonium chloride (Aliquat 336: manufactured by Aldrich) 0.15 mL (0.33 mmol) and toluene 35 mL were added, and the liquid temperature was kept at 25 to 35 ° C., while maintaining 20 wt% sodium hydroxide. 10.1 g (50.5 mmol) of an aqueous solution was slowly added dropwise over 50 minutes and reacted at the same temperature for 3 hours. Thereafter, 0.14 mL (0.85 mmol) of 98% pure diethyl cyanomethylphosphonate was added and reacted at the same temperature for 66 hours. After completion of the reaction, 5 mL of water was added and stirred for 30 minutes. To the resulting reaction solution, 50 mL of toluene was added, the organic layer was separated, washed with 10 mL of a 10 wt% aqueous sodium hydroxide solution, and 10 mL of saturated brine was added. Subsequently, 5.6 mL of 1 mol / L hydrochloric acid was added for neutralization, and then the organic layer was taken out and transferred to a glass flask having an internal volume of 200 mL equipped with a stirrer. 1.60 g of anhydrous sodium sulfate was added thereto and stirred at room temperature for 1 hour. Further, 0.14 g of activated carbon (powder: Wako Pure Chemical Industries, Ltd.) and silica gel (Wakogel C-200: Wako Pure Chemical Industries, Ltd.) After adding 0.62 g and stirring at room temperature for 1.75 hours, the mixture was filtered through celite, and the celite was washed with 50 mL of toluene. When the obtained reaction solution was concentrated under reduced pressure, crystals were precipitated. The crystals were heated and dissolved, and then 30 mL of hexane was added and heated to reflux for 30 minutes. Thereafter, when the liquid temperature was cooled to 5 ° C. and stirred for 2 hours, crystals were precipitated. After filtering the crystals, the crystals were washed with 30 mL of hexane and dried at 55 ° C. under reduced pressure to give 3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] to give prop-2-ene nitrile 4.81 g (90% yield).
[0021]
The resulting 3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] then marks the physical properties of the prop-2-ene nitrile.
Melting point: 175-176 ° C., EI-MS (m / e): 313 (M−1), CI-MS (m / e): 315 (M + 1)
[0022]
[Example 1] Production of 3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] prop-2-enal 200 g of glass with a stirrer, a thermometer and a dropping funnel the flask under a nitrogen atmosphere, the synthesized 3 in reference example 1 [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] prop-2-ene nitrile 4.0 g (12.7 mmol), 1.6 g (25.4 mmol) of ammonium formate, 4.4 g (37.5 mmol as nickel atom) and acetic acid with water-containing developed Raney nickel (manufactured by Kawaken Fine Chemical Co., Ltd .: NDHT-90: nickel content 50% by weight) 40 mL was added and reacted at 65 ° C. for 4 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, 20 mL of ethanol was added, and the catalyst was filtered through celite. Next, the filtrate was concentrated under reduced pressure, 40 mL of ethyl acetate was added, 1 mol / L hydrochloric acid 5 mL, water 10 mL, 1 mol / L sodium hydroxide aqueous solution 20 mL, DL-tartaric acid alkaline aqueous solution (DL-tartaric acid 1.0 g After washing with 14 mL of a 1 mol / L aqueous sodium hydroxide solution and 20 mL of saturated brine in that order, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure and 3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] prop-2 having a purity of 98% (area percentage by high performance liquid chromatography) as pale yellow crystals. -3.4 g of enal was obtained (82% yield).
[0023]
The physical properties of 3- [2-cyclopropyl-4- (4-fluorophenyl) -3-quinolyl] prop-2-enal are described below.
CI-MS (m / e): 318 (M + 1)
1 H-NMR (CDCl 3 , δ (ppm)): 1.07 to 1.13 (2H, m), 1.40 to 1.45 (2H, m), 2.32 to 2.37 (1H, m), 6.43 (1H, dd, J = 7.8, 16.2 Hz), 7.22 to 7.26 (4H, m), 7.35 to 7.38 (2H, m), 7. 55 (1H, d, J = 16.2 Hz), 7.64-7.69 (1 H, m), 7.97 (1 H, d, J = 8.4 Hz), 9.51 (1 H, d, J = 7.5Hz)
[0024]
【The invention's effect】
According to the production method of the present invention, the quinolylpropenal derivative of the formula (2) can be produced in a high yield from the quinolylacrylonitrile derivative of the formula (1) by a simple method. Accordingly, it is possible to provide an industrially advantageous method for producing quinolyl acrolein.
Claims (3)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000014849A JP4496585B2 (en) | 2000-01-24 | 2000-01-24 | Process for producing quinolylpropenal |
| EP01901538A EP1251124B1 (en) | 2000-01-24 | 2001-01-24 | Process for the preparation of quinolylpropenal |
| DE60129203T DE60129203T2 (en) | 2000-01-24 | 2001-01-24 | PROCESS FOR THE PREPARATION OF QUINOLYLPROPENAL |
| CA002398138A CA2398138C (en) | 2000-01-24 | 2001-01-24 | Process for the preparation of quinolylpropenal |
| CN01807062.0A CN1222512C (en) | 2000-01-24 | 2001-01-24 | Process for the preparation of quinolylpropenal |
| AT01901538T ATE366239T1 (en) | 2000-01-24 | 2001-01-24 | METHOD FOR PRODUCING QUINOLYL PROPENAL |
| PCT/JP2001/000452 WO2001053265A1 (en) | 2000-01-24 | 2001-01-24 | Process for the preparation of quinolylpropenal |
| US10/181,820 US6630591B2 (en) | 2000-01-24 | 2001-01-24 | Process for the preparation of quinolylpropenal |
| AU2001227100A AU2001227100A1 (en) | 2000-01-24 | 2001-01-24 | Process for the preparation of quinolylpropenal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000014849A JP4496585B2 (en) | 2000-01-24 | 2000-01-24 | Process for producing quinolylpropenal |
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| Publication Number | Publication Date |
|---|---|
| JP2001199964A JP2001199964A (en) | 2001-07-24 |
| JP2001199964A5 JP2001199964A5 (en) | 2006-11-30 |
| JP4496585B2 true JP4496585B2 (en) | 2010-07-07 |
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| JP2000014849A Expired - Fee Related JP4496585B2 (en) | 2000-01-24 | 2000-01-24 | Process for producing quinolylpropenal |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01279866A (en) * | 1987-08-20 | 1989-11-10 | Nissan Chem Ind Ltd | Quinoline-based mevalonolactones |
| JPH06329540A (en) * | 1991-10-04 | 1994-11-29 | Nissan Chem Ind Ltd | Suppressor for arteriosclerotic intravascular membrane hyperplasia |
| JP4281248B2 (en) * | 1998-07-23 | 2009-06-17 | 日産化学工業株式会社 | Process for producing quinoline derivative and intermediate |
-
2000
- 2000-01-24 JP JP2000014849A patent/JP4496585B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01279866A (en) * | 1987-08-20 | 1989-11-10 | Nissan Chem Ind Ltd | Quinoline-based mevalonolactones |
| JPH06329540A (en) * | 1991-10-04 | 1994-11-29 | Nissan Chem Ind Ltd | Suppressor for arteriosclerotic intravascular membrane hyperplasia |
| JP4281248B2 (en) * | 1998-07-23 | 2009-06-17 | 日産化学工業株式会社 | Process for producing quinoline derivative and intermediate |
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| JP2001199964A (en) | 2001-07-24 |
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