JPH0778033B2 - 2,4,5-Trifluoro-3-hydroxybenzoic acid and method for producing the same - Google Patents
2,4,5-Trifluoro-3-hydroxybenzoic acid and method for producing the sameInfo
- Publication number
- JPH0778033B2 JPH0778033B2 JP62303312A JP30331287A JPH0778033B2 JP H0778033 B2 JPH0778033 B2 JP H0778033B2 JP 62303312 A JP62303312 A JP 62303312A JP 30331287 A JP30331287 A JP 30331287A JP H0778033 B2 JPH0778033 B2 JP H0778033B2
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- trifluoro
- group
- acid
- hydroxybenzoic acid
- carbon atoms
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Description
【発明の詳細な説明】 ［発明の目的］ （産業上の利用分野） 本発明は、新規物質2,4,5−トリフルオロ−３−ヒドロ
キシ安息香酸及びその製造法に関し、更に詳しくは、キ
ノロンカルボン酸系抗菌剤の合成中間体として有用な2,
4,5−トリフルオロ−３−ヒドロキシ安息香酸及びその
製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] (Field of Industrial Application) The present invention relates to a novel substance 2,4,5-trifluoro-3-hydroxybenzoic acid and a method for producing the same, more specifically, quinolone. Useful as a synthetic intermediate for carboxylic acid antibacterial agents 2.
The present invention relates to 4,5-trifluoro-3-hydroxybenzoic acid and a method for producing the same.
（従来の技術及びその問題点） 従来、合成抗菌剤としては、 次式： で示されるナリジクス酸、 次式： で示されるピペミド酸、 次式： で示されるピロミド酸及び 次式： で示されるノルフロキサシン等が開発され、各種感染症
の治療に供されている。(Conventional Technology and Problems Thereof) Conventional synthetic antibacterial agents have the following formula: Nalidixic acid represented by the following formula: Pipemidic acid represented by the following formula: And the following formula: Norfloxacin and the like shown in have been developed and used for the treatment of various infectious diseases.
更に、前記抗菌剤の種々の特性を改良するものとして、
８位に酸素原子を有するキノロンカルボン酸系抗菌剤が
開発されている（例えば，特公昭61−11955号）。Further, as improving various properties of the antibacterial agent,
A quinolonecarboxylic acid type antibacterial agent having an oxygen atom at the 8-position has been developed (for example, Japanese Patent Publication No. 61-11955).
しかしながら、８位に酸素原子を有するキノロンカルボ
ン酸誘導体の合成には、多工程を要し、製造工程の短縮
が望まれている。However, synthesis of a quinolonecarboxylic acid derivative having an oxygen atom at the 8-position requires multiple steps, and it is desired to shorten the manufacturing steps.
次式（Ｉ）： で示される2,4,5−トリフルオロ−３−ヒドロキシ安息
香酸は、前記キノロンカルボン酸誘導体の合成中間体と
して有用と考えられる。Formula (I): It is considered that 2,4,5-trifluoro-3-hydroxybenzoic acid represented by is useful as a synthetic intermediate for the quinolonecarboxylic acid derivative.
しかしながら、2,3,4,5−テトラフルオロ安息香酸にRO-
又はOH-等の求核試剤を反応させても、カルボキシル基
のメタ位への求核反応は起こらず、すべてパラ位又はオ
ルト位に選択的に反応し、2,4,5−トリフルオロ−３−
ヒドロキシ安息香酸を得ることはできない。また、他の
方法によっても、2,4,5−トリフルオロ−３−ヒドロキ
シ安息香酸は得られていない。However, RO to 2,3,4,5-tetrafluoro-benzoic acid -
Or OH - even when the nucleophile is reacted in such a nucleophilic reaction to the meta-position of the carboxyl group it does not occur, all selectively reacts in the para position or ortho position, 2,4,5 - 3-
It is not possible to obtain hydroxybenzoic acid. Moreover, 2,4,5-trifluoro-3-hydroxybenzoic acid has not been obtained by any other method.
［発明の構成］ （問題点を解決するための手段及び作用） 本発明は、新規化合物2,4,5−トリフルオロ−３−ヒド
ロキシ安息香酸及びその塩並びにそれらの製造法に関す
るものである。[Structure of the Invention] (Means and Actions for Solving Problems) The present invention relates to a novel compound 2,4,5-trifluoro-3-hydroxybenzoic acid and a salt thereof, and a method for producing them.
本発明の化合物は、例えば、次のようにして製造するこ
とができる。The compound of the present invention can be produced, for example, as follows.
即ち、次式（II）： （式中、Ｒは水素原子又は加水分解により水酸基を形成
しうる有機基を表す。） で示される化合物を水又は水性溶媒中において、80〜23
0℃で自然発生圧力下に処理することにより目的化合物
を得ることができる。That is, the following formula (II): (In the formula, R represents a hydrogen atom or an organic group capable of forming a hydroxyl group by hydrolysis.) A compound represented by the formula 80 to 23 in water or an aqueous solvent.
The target compound can be obtained by treating at 0 ° C. under a spontaneously generated pressure.
前記反応において、原料化合物（II）のＲが有機基であ
る場合、本反応は3,5,6−トリフルオロ−４−ヒドロキ
シフタル酸を経由し、その後、水酸基のパラ位のカルボ
キシル基のみが選択的に脱炭酸し、目的化合物（Ｉ）を
与える。従って、前記式（II）におけるＲとしての有機
基は、加水分解により水酸基を形成するものであれば如
何なるものでもよいが、特に、炭素数１〜６のアルキル
基、炭素数７〜10のアラルキル基、炭素数５〜10のシク
ロアルキル基又は炭素数１〜10のアシル基であることが
好ましい。In the above reaction, when R of the raw material compound (II) is an organic group, this reaction goes through 3,5,6-trifluoro-4-hydroxyphthalic acid, and then only the carboxyl group at the para position of the hydroxyl group is present. Selective decarboxylation gives the target compound (I). Therefore, the organic group as R in the formula (II) may be any group as long as it forms a hydroxyl group by hydrolysis, and particularly, an alkyl group having 1 to 6 carbon atoms and an aralkyl group having 7 to 10 carbon atoms. A group, a cycloalkyl group having 5 to 10 carbon atoms or an acyl group having 1 to 10 carbon atoms is preferable.
前記炭素数１〜６のアルキル基としては、例えば、メチ
ル基、エチル基、プロピル基、イソプロピル基、ブチル
基、イソブチル基、sec−ブチル基、tert−ブチル基、
ペンチル基、ヘキシル基等が挙げられる。Examples of the alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group,
Examples thereof include a pentyl group and a hexyl group.
前記炭素数７〜10のアラルキル基としては、例えば、ベ
ンジル基、ｐ−クロロフェニルメチル基等が挙げられ
る。Examples of the aralkyl group having 7 to 10 carbon atoms include benzyl group and p-chlorophenylmethyl group.
前記炭素数５〜10のシクロアルキル基としては、例え
ば、シクロペンチル基、シクロヘキシル基等が挙げられ
る。Examples of the cycloalkyl group having 5 to 10 carbon atoms include cyclopentyl group and cyclohexyl group.
前記炭素数１〜10のアシル基としては、ホルミル基、ア
セチル基、ベンゾイル基、プロピオニル基、ブチニル基
等が挙げられる。Examples of the acyl group having 1 to 10 carbon atoms include formyl group, acetyl group, benzoyl group, propionyl group and butynyl group.
原料化合物（II）の具体例としては、例えば、3,5,6−
トリフルオロ−４−ヒドロキシフタル酸、3,5,6−トリ
フルオロ−４−メトキシフタル酸、3,5,6−トリフルオ
ロ−４−エトキシフタルサン、3,5,6−トリフルオロ−
４−プロポキシフタル酸、、3,5,6−トリフルオロ−４
−ブトキシフタル酸、3,5,6−トリフルオロ−４−ベン
ジルオキシフタル酸、3,5,6−トリフルオロ−４−アセ
トキシフタル酸、3,5,6−トリフルオロ−４−ベンゾイ
ルオキシフタル酸等が挙げられる。Specific examples of the raw material compound (II) include, for example, 3,5,6-
Trifluoro-4-hydroxyphthalic acid, 3,5,6-trifluoro-4-methoxyphthalic acid, 3,5,6-trifluoro-4-ethoxyphthalsan, 3,5,6-trifluoro-
4-propoxyphthalic acid, 3,5,6-trifluoro-4
-Butoxyphthalic acid, 3,5,6-trifluoro-4-benzyloxyphthalic acid, 3,5,6-trifluoro-4-acetoxyphthalic acid, 3,5,6-trifluoro-4-benzoyloxyphthalic acid Acid etc. are mentioned.
かかる原料化合物（II）の合成法は、例えば、石川他，
日本化学会誌200頁（1976年）に記載されている。The method for synthesizing the starting compound (II) is described in, for example, Ishikawa et al.
It is described in page 200 (1976) of the Chemical Society of Japan.
本発明の製造法において、溶媒の量は、原料化合物（I
I）に対して３〜100重量倍の範囲内であることが好まし
い。水性溶媒としては水及び水と任意の割合で溶解し、
酸性条件下において反応しない溶媒との混合物が使用で
きる。水性溶媒の具体例としてはメタノール、エタノー
ル等のアルコール類、ジオキサン等のエーテル類と水と
の混合物が挙げられる。水の含有量は10％以上が好まし
い。反応は80〜230℃の範囲内で自然発生圧力下に行う
が、反応温度が100〜190℃の範囲内であることが更に好
ましい。反応時間は反応温度に依存するが、通常、0.5
〜20時間で完結する。本反応は、不活性ガス、例えば、
窒素、アルゴンの存在下で行ってもよい。In the production method of the present invention, the amount of the solvent is
It is preferably in the range of 3 to 100 times the weight of I). As an aqueous solvent, it dissolves in water and water at an arbitrary ratio,
Mixtures with solvents that do not react under acidic conditions can be used. Specific examples of the aqueous solvent include a mixture of alcohols such as methanol and ethanol, ethers such as dioxane, and water. The water content is preferably 10% or more. The reaction is carried out under the pressure of spontaneous generation within the range of 80 to 230 ° C, and the reaction temperature is more preferably within the range of 100 to 190 ° C. The reaction time depends on the reaction temperature, but is usually 0.5
It will be completed in ~ 20 hours. This reaction is carried out with an inert gas such as
It may be carried out in the presence of nitrogen or argon.
反応生成物は、冷却後、反応混合物を濃縮すると結晶又
は粉末として析出するので、過等通常の方法で単離可
能である。After cooling, the reaction product is precipitated as crystals or powder when the reaction mixture is concentrated, and thus can be isolated by a conventional method.
（実施例） 以下、本発明を実施例により具体的に説明するが本発明
はこれらに限定されるものではない。(Examples) Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited thereto.
実施例１ 3,5,6−トリフルオロ−４−ヒドロキシフタル酸0.47g及
び水10mlを封管中にいれ、窒素置換して140℃で３時間
加熱した。反応終了後、室温まで冷却し、濃縮すると結
晶が析出した。その結晶をろ過し、洗浄（クロロホルム
5ml）後、乾燥した。無色の結晶として2,4,5−トリフル
オロ−３−ヒドロキシ安息香酸0.35gを得た。収率90
％。融点144〜146℃。プロトンNMRスペクトル（inCD3O
D）δppm7.25（m,1H,3JHF10.74Hz,4JHF8.30Hz,4JHF5.86
Hz）芳香族プロトン、4.94（bs,1H）ヒドロキシプロト
ン、質量分析M+192。Example 1 0.47 g of 3,5,6-trifluoro-4-hydroxyphthalic acid and 10 ml of water were placed in a sealed tube, which was replaced with nitrogen and heated at 140 ° C. for 3 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated to precipitate crystals. The crystals are filtered and washed (chloroform
5 ml) and then dried. 0.35 g of 2,4,5-trifluoro-3-hydroxybenzoic acid was obtained as colorless crystals. Yield 90
%. Melting point 144-146 ° C. Proton NMR spectrum (in CD 3 O
D) δppm 7.25 (m, 1H, 3 J HF 10.74Hz, 4 J HF 8.30Hz, 4 J HF 5.86
Hz) aromatic proton, 4.94 (bs, 1H) hydroxy proton, mass spec M + 192.
実施例２ 3,5,6−トリフルオロ−４−メトキシフタル酸0.84g及び
水10mlを封管中にいれ、窒素置換して190℃で８時間加
熱した。反応終了後、室温まで冷却し、濃縮すると結晶
が析出した。その結晶をろ過し、洗浄（クロロホルム5m
l）後、乾燥した。無色の結晶として2,4,5−トリフルオ
ロ−３−ヒドロキシ安息香酸0.48gを得た。収率74％。
融点144〜146℃。プロトンNMRスペクトル（inCD3OD）δ
ppm7.25（m,1H,3JHF10.74Hz,4JHF8.30Hz,4JHF5.86Hz）
芳香族プロトン、4.94（bs,1H）ヒドロシプロトン。質
量分析M+192。Example 2 0.84 g of 3,5,6-trifluoro-4-methoxyphthalic acid and 10 ml of water were placed in a sealed tube, which was replaced with nitrogen and heated at 190 ° C. for 8 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated to precipitate crystals. The crystals are filtered and washed (chloroform 5m
l) and then dried. 0.48 g of 2,4,5-trifluoro-3-hydroxybenzoic acid was obtained as colorless crystals. Yield 74%.
Melting point 144-146 ° C. Proton NMR spectrum (inCD 3 OD) δ
ppm7.25 (m, 1H, 3 J HF 10.74Hz, 4 J HF 8.30Hz, 4 J HF 5.86Hz)
Aromatic proton, 4.94 (bs, 1H) Hydroxyproton. Mass Spec M + 192.
参考例 2,4,5−トリフルオロ−３−ヒドロキシ安息香酸（Ｉ）
を出発原料として、抗菌剤オフロキサシン（III）（９
−フルオロ−３−メチル−10−（４−メチル−１−ピペ
ラジニル）−７−オキソ−2,3−ジヒドロ−7H−ピリド
［1,2,3−de］［1,4］ベンゾオキサジン−６−カルボン
酸）を合成する際の重要な中間体である9,10−ジフルオ
ロ−３−メチル−７−オキソ−2,3−ジヒドロ−7H−ピ
リド［1,2,3−de］［1,4］ベンゾオキサジン−６−カル
ボン酸エチル（IV）を下記の反応式に従って合成した。Reference example 2,4,5-trifluoro-3-hydroxybenzoic acid (I)
Using the starting material as a starting material, the antibacterial agent ofloxacin (III) (9)
-Fluoro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6 -Carboxylic acid), which is an important intermediate in the synthesis of 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1, 4] Ethyl (IV) benzoxazine-6-carboxylate was synthesized according to the following reaction formula.
工程１ 2,4,5−トリフルオロ−３−ヒドロキシ安息香酸（Ｉ）1
2,6g（0.066モル）に無水酢酸40mlを添加し、15時間加
熱還流した。反応混合物を氷水中に注加後、クロロホル
ムで抽出し、クロロホルム層を水洗し、乾燥した後、減
圧濃縮し、残渣をｎ−ヘキサンで洗浄することにより、
３−アセトキシ−2,4,5−トリフルオロ安息香酸（Ｖ）
6.10gを無色粉末として得た。 Step 1 2,4,5-Trifluoro-3-hydroxybenzoic acid (I) 1
40 ml of acetic anhydride was added to 2,6 g (0.066 mol), and the mixture was heated under reflux for 15 hours. The reaction mixture was poured into ice water, extracted with chloroform, the chloroform layer was washed with water, dried and concentrated under reduced pressure, and the residue was washed with n-hexane,
3-acetoxy-2,4,5-trifluorobenzoic acid (V)
6.10 g was obtained as a colorless powder.
質量分析（CI）:m/e 235（M+＋１）,217（M+−OH）,17
5（M+−CH3COO） 工程２〜６ ３−アセトキシ−2,4,5−トリフルオロ安息香酸（Ｖ）
6.10g（0.026モル）をベンゼン200mlに溶解し、塩化チ
オニル15mlを加えて４時間加熱還流した。反応後、ベン
ゼン及び過剰の塩化チオニルを完全に減圧留去し、３−
アセトキシ−2,4,5−トリフルオロ安息香酸クロリド（V
I）を得た。Mass spectrum (CI): m / e 235 (M + +1), 217 (M + -OH), 17
5 (M + -CH 3 COO) Step 2-6 3-acetoxy-2,4,5-trifluorobenzoic acid (V)
6.10 g (0.026 mol) was dissolved in 200 ml of benzene, 15 ml of thionyl chloride was added, and the mixture was heated under reflux for 4 hours. After the reaction, benzene and excess thionyl chloride were completely distilled off under reduced pressure, and 3-
Acetoxy-2,4,5-trifluorobenzoic acid chloride (V
I) got.
一方、マグネシウムエトキシド3.17g（0.028モル）及び
マロン酸ジエチル4.30g（0.027モル）を無水ジエチルエ
ーテル100ml中で３時間加熱還流することによって、エ
トキシマグネシウムマロン酸ジエチルのジエチルエーテ
ル懸濁液を得た。これに、撹拌下室温で前記酸クロリド
の無水ジエチルエーテル50ml溶液を滴下し、滴下終了
後、更に室温で１時間撹拌した。反応終了後、1N塩酸を
加えて酸性として酢酸エチルで抽出し、有機層を水洗
し、乾燥した後、溶媒を減圧留去し、３−アセトキシ−
2,4,5−トリフルオロベンゾイルマロン酸ジエチル（VI
I）10.39gを黄色油状物として得た。Meanwhile, 3.17 g (0.028 mol) of magnesium ethoxide and 4.30 g (0.027 mol) of diethyl malonate were heated under reflux in 100 ml of anhydrous diethyl ether for 3 hours to obtain a suspension of diethyl ethoxymagnesium malonate in diethyl ether. . To this, a solution of the acid chloride in 50 ml of anhydrous diethyl ether was added dropwise with stirring at room temperature, and after completion of the addition, the mixture was further stirred at room temperature for 1 hour. After completion of the reaction, 1N hydrochloric acid was added to acidify and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried, and the solvent was evaporated under reduced pressure to give 3-acetoxy-
Diethyl 2,4,5-trifluorobenzoylmalonate (VI
I) 10.39 g was obtained as a yellow oil.
次しで、この黄色油状物をジオキサン120mlに溶解し、
ｐ−トルエンスルホン酸・一水和物4.90g（0.026モル）
を添加し、15時間加熱還流した。反応終了後、ジオキサ
ンを減圧留去し、残渣に水100ml及び炭酸水素ナトリウ
ム2.15g（0.026モル）を加え、この混合物をクロロホル
ムで抽出した。クロロホルム層を水洗し、乾燥した後、
減圧留去し、３−アセトキシ−2,4,5−トリフルオロベ
ンゾイル酢酸エチル（VIII）7.64gを赤色油状物として
得た。This yellow oil was then dissolved in 120 ml dioxane,
p-toluenesulfonic acid monohydrate 4.90 g (0.026 mol)
Was added and the mixture was heated under reflux for 15 hours. After completion of the reaction, dioxane was distilled off under reduced pressure, 100 ml of water and 2.15 g (0.026 mol) of sodium hydrogencarbonate were added to the residue, and this mixture was extracted with chloroform. After washing the chloroform layer with water and drying,
Evaporation under reduced pressure gave 7.64 g of ethyl 3-acetoxy-2,4,5-trifluorobenzoylacetate (VIII) as a red oil.
このようにして３−アセトキシ−2,4,5−トリフルオロ
ベンゾイル酢酸エチル（VIII）7.64g（0.025モル）に無
水酢酸20ml及びオルトギ酸エチル6mlを添加し、２時間
加熱還流後、減圧濃縮した。残渣をジクロロメタン50ml
に溶解し、DL−２−アミノプロパノール1.91g（0.026モ
ル）を添加して室温で一夜放置した。ジクロロメタンを
減圧留去し、残渣をシリカゲルカラムクロマトグラフィ
ー（溶媒：トルエン−酢酸エチルの1:1混合液）に付
し、２−（３−アセトキシ−2,4,5−トリフルオロベン
ゾイル）−３−（２−ヒドロキシ−１−メチルエチル）
アミノアクリル酸エチル（Ｘ）4.37gを微黄色油状物と
して得た。Thus, 20 ml of acetic anhydride and 6 ml of ethyl orthoformate were added to 7.64 g (0.025 mol) of ethyl 3-acetoxy-2,4,5-trifluorobenzoylacetate (VIII), and the mixture was heated under reflux for 2 hours and concentrated under reduced pressure. . 50 ml of the residue is dichloromethane
Was dissolved in the solution, 1.91 g (0.026 mol) of DL-2-aminopropanol was added, and the mixture was allowed to stand at room temperature overnight. Dichloromethane was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (solvent: toluene-ethyl acetate 1: 1 mixture) to give 2- (3-acetoxy-2,4,5-trifluorobenzoyl) -3. -(2-hydroxy-1-methylethyl)
Obtained 4.37 g of ethyl aminoacrylate (X) as a pale yellow oil.
質量分析:m/e 389（M+）,358（M+−CH2OH）,43（＋COC
H3） 工程７ 前述のように得た２−（３−アセトキシ−2,4,5−トリ
フルオロベンゾイル）−３−（２−ヒドロキシ−１−メ
チルエチル）アミノアクリル酸エチル（Ｘ）4.30g（0.0
11モル）をジメチルホルムアミド30mlに溶解し、フッ化
カリウム1.92g（0.033モル）を添加し、140〜150℃で２
時間撹拌した。反応終了後、溶媒を減圧留去し、残渣に
水を加えてジクロロメタンで抽出し、有機層を水洗し、
乾燥した後、減圧濃縮した。Mass spectrometry: m / e 389 (M + ), 358 (M + −CH 2 OH), 43 (+ COC
H 3) Step 7 2- (3-acetoxy-2,4,5-trifluorobenzoyl Robben benzoyl obtained as described above) -3- (2-hydroxy-1-methylethyl) aminoethyl acrylate (X) 4.30 g (0.0
11 mol) was dissolved in 30 ml of dimethylformamide, 1.92 g (0.033 mol) of potassium fluoride was added, and the mixture was heated at 140 to 150 ° C for 2 hours.
Stir for hours. After completion of the reaction, the solvent was distilled off under reduced pressure, water was added to the residue and the mixture was extracted with dichloromethane, and the organic layer was washed with water,
After drying, it was concentrated under reduced pressure.
次いで、残留物をエタノールで洗浄し、得られた粗結晶
をアセトンから再結晶して9,10−ジフルオロ−３−メチ
ル−７−オキソ−2,3−ジヒドロ−7H−ピリド［1,2,3−
de］［1,4］ベンゾオキサジン−６−カルボン酸エチル
（IV）1.40gを微褐色微細針状結晶として得た。The residue was then washed with ethanol and the crude crystals obtained were recrystallized from acetone to give 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2, 3-
1.40 g of de] [1,4] benzoxazine-6-carboxylate ethyl (IV) was obtained as fine brown fine needle crystals.
融点:255〜256℃ 元素分析値（％）:C15H13F2NO4として Ｃ Ｈ Ｎ 理論値 58.25 4.24 4.53 測定値 58.09 4.14 4.24 ［発明の効果］ 本発明によれば、抗菌剤として有用なキノロンカルボン
酸誘導体の合成中間体として有用な新規化合物2,4,5−
トリフルオロ−３−ヒドロキシ安息香酸を提供でき、該
化合物を用いることにより、前記キノロンカルボン酸誘
導体の製造工程を大幅に短縮できる。Melting point: 255 to 256 ° C Elemental analysis value (%): C 15 H 13 F 2 NO 4 CHN theoretical value 58.25 4.24 4.53 measured value 58.09 4.14 4.24 [Effect of the invention] Useful as an antibacterial agent according to the present invention Compounds useful as synthetic intermediates of novel quinolonecarboxylic acid derivatives 2,4,5-
Trifluoro-3-hydroxybenzoic acid can be provided, and by using the compound, the production process of the quinolonecarboxylic acid derivative can be significantly shortened.
Claims (1)
香酸及びその塩。 （２）式（II）： （式中、Ｒは水素原子又は炭素数１〜６のアルキル基、
炭素数７〜10のアラルキル基、炭素数５〜10のシクロア
ルキル基又は炭素数１〜10のアシル基を表す。） で示される化合物を水又は水性溶媒中において、80〜23
0℃で自然発生圧力下に処理することを特徴とする次式
（Ｉ）： で示される2,4,5−トリフルオロ−３−ヒドロキシ安息
香酸又はその塩の製造法。1. The following formula (I): 2,4,5-trifluoro-3-hydroxybenzoic acid and a salt thereof. (2) Formula (II): (In the formula, R is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms,
It represents an aralkyl group having 7 to 10 carbon atoms, a cycloalkyl group having 5 to 10 carbon atoms, or an acyl group having 1 to 10 carbon atoms. ) In water or an aqueous solvent, a compound represented by
The following formula (I) is characterized in that the treatment is carried out at 0 ° C. under a spontaneous pressure: 2. A method for producing 2,4,5-trifluoro-3-hydroxybenzoic acid or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62303312A JPH0778033B2 (en) | 1986-12-04 | 1987-12-02 | 2,4,5-Trifluoro-3-hydroxybenzoic acid and method for producing the same |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61-287763 | 1986-12-04 | ||
| JP28776386 | 1986-12-04 | ||
| JP62303312A JPH0778033B2 (en) | 1986-12-04 | 1987-12-02 | 2,4,5-Trifluoro-3-hydroxybenzoic acid and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63264440A JPS63264440A (en) | 1988-11-01 |
| JPH0778033B2 true JPH0778033B2 (en) | 1995-08-23 |
Family
ID=26556868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62303312A Expired - Lifetime JPH0778033B2 (en) | 1986-12-04 | 1987-12-02 | 2,4,5-Trifluoro-3-hydroxybenzoic acid and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0778033B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0610159B2 (en) * | 1987-06-29 | 1994-02-09 | 株式会社日本触媒 | Process for producing 3-hydroxy-2,4,5-trifluorobenzoic acid |
| JPH03279348A (en) * | 1990-03-28 | 1991-12-10 | Kyorin Pharmaceut Co Ltd | Production of 2,4,5-trifluoro-3-alkoxybenzoic acid |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6185349A (en) * | 1984-10-04 | 1986-04-30 | Nippon Shokubai Kagaku Kogyo Co Ltd | Production of 2,3,4,5-tetrafluorobenzoic acid |
| JPS62175485A (en) * | 1985-12-23 | 1987-08-01 | アボツト ラボラトリ−ズ | Isoxazolo-pyrido-benzoxazine and isothiazolo-pyrido- benzoxazine derivative |
| JPH089597B2 (en) * | 1986-01-21 | 1996-01-31 | 杏林製薬株式会社 | 8-Alkoxyquinolonecarboxylic acid excellent in selective toxicity and its salt, and method for producing the same |
-
1987
- 1987-12-02 JP JP62303312A patent/JPH0778033B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63264440A (en) | 1988-11-01 |
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