JPH0558955A - Production of beta-fluoro-alpha-keto acid equivalent substance - Google Patents
Production of beta-fluoro-alpha-keto acid equivalent substanceInfo
- Publication number
- JPH0558955A JPH0558955A JP3244246A JP24424691A JPH0558955A JP H0558955 A JPH0558955 A JP H0558955A JP 3244246 A JP3244246 A JP 3244246A JP 24424691 A JP24424691 A JP 24424691A JP H0558955 A JPH0558955 A JP H0558955A
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- beta
- acid
- reagent
- toluenesulfonyloxy
- 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
Classifications
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【産業上の利用分野】本発明は、医薬農薬等の生理活性
物質、液晶や界面活性剤等の機能性有機化合物、機能性
材料ポリマー等の原料として有用なβ-フルオロ-α-ケ
ト酸の等価体である含フッ素エノールエステル化合物の
製造方法に関する。The present invention relates to a β-fluoro-α-keto acid useful as a raw material for physiologically active substances such as pharmaceuticals and agricultural chemicals, functional organic compounds such as liquid crystals and surfactants, and functional material polymers. The present invention relates to a method for producing an equivalent fluorine-containing enol ester compound.
【0002】[0002]
【従来の技術】一般に機能性或いは生理活性を有する既
知化合物の水素をフッ素に置き換えた化合物は、そのフ
ッ素原子の特異的な電子効果により、その機能や生理活
性が強化され、或いは新しい機能や生理活性を得ること
が知られている。そのため既知化合物の原料と類似の構
造を持つ含フッ素ビルディングブロックが設計され合成
されてきている〔例えば、「90年代のフッ素系生理活
性物質」石川延男監修、CMC社刊(1991)〕。2. Description of the Related Art In general, a compound obtained by replacing hydrogen of a known compound having functionality or physiological activity with fluorine has its function or physiological activity enhanced by a specific electronic effect of the fluorine atom, or has a new function or physiological activity. It is known to obtain activity. Therefore, a fluorine-containing building block having a structure similar to the starting material of a known compound has been designed and synthesized [eg, "Fluorine-based physiologically active substances in the 90's, supervised by Nobuo Ishikawa, published by CMC (1991)].
【0003】α-ケト酸は一般に良く用いられる化学原
料物質のひとつであり、特には種々の生理活性物質や医
薬の原料として広く用いられているアミノ酸の原料とな
る。そのフッ素置換化合物であるβ-フルオロ-α-ケト
酸及びその等価体は有用な原料化合物と考えられてい
る。[0003] α-Keto acid is one of the commonly used chemical raw materials, and in particular, it is a raw material of various physiologically active substances and amino acids which are widely used as raw materials for pharmaceuticals. The fluorine-substituted compound β-fluoro-α-keto acid and its equivalent are considered to be useful starting compounds.
【0004】このβ-フルオロ-α-ケト酸、その等価
体、或いはβ-フルオロアミノ酸の既知の製造方法とし
ては、 フッ素化試薬により、水酸基、チオール基、アミノ基
などをフッ素に置き換える方法〔例えば J.Kollonitsc
h, S.Marburg, L.M.Perkins, J.Org.Chem., 40,3808(19
75); 40,771(1979)〕、 二重結合に対してフッ素を導入する方法〔例えば、H.
Gershon, M.W.McNeil, E.D.Bergmann, J.Med.Chem.16,1
407(1973)〕、 アジリジン環、エポキシ環などをフッ化水素で開環
し、その後目的物に変換する方法〔例えば、A.I.Ayi,
M.Remli, R.Guedj, J.Fluorine Chem.18,93(1981)〕、 α-ケト酸のβ-位の水素をフッ素と反応させる方法
〔例えば、T.Tsusima, K.Kawada, T.Tsuji, J.Org.Che
m.,47,1107(1967)〕、等が知られている。As a known method for producing this β-fluoro-α-keto acid, its equivalent, or β-fluoro amino acid, a method of replacing a hydroxyl group, a thiol group, an amino group or the like with fluorine by a fluorinating reagent [eg, J. Kollonitsc
h, S. Marburg, LMPerkins, J. Org. Chem., 40, 3808 (19
75); 40, 771 (1979)], a method of introducing fluorine into the double bond (for example, H.
Gershon, MWMcNeil, EDBergmann, J.Med.Chem.16,1
407 (1973)], aziridine ring, epoxy ring and the like is opened with hydrogen fluoride, then a method of converting to the desired product [eg, AIAyi,
M. Remli, R. Guedj, J. Fluorine Chem. 18, 93 (1981)], a method of reacting the β-position hydrogen of α-keto acid with fluorine (for example, T. Tsusima, K. Kawada, T. Tsuji, J.Org.Che
m., 47, 1107 (1967)], etc. are known.
【0005】しかし、これらの方法では、種々のβ-フ
ルオロ-α-ケト酸またはその等価体を作るためにはそれ
に対応した含フッ素原料を揃える必要があり、必ずしも
簡便な方法とは言い難い。このような煩雑さを避け、種
々のβ-フルオロ-α-ケト酸またはその等価体を合成す
るためには、β-フルオロ-α-ケト酸部分をひとつの合
成原料ブロックとして種々の置換基をそれに対して導入
する方法が最適と考えられる。However, in these methods, in order to prepare various β-fluoro-α-keto acids or their equivalents, it is necessary to prepare fluorine-containing raw materials corresponding thereto, which is not necessarily a simple method. In order to avoid such complications and synthesize various β-fluoro-α-keto acids or their equivalents, various substituents are used with the β-fluoro-α-keto acid moiety as one synthesis raw material block. The method introduced for this is considered optimal.
【0006】[0006]
【発明が解決しようとする課題】本発明は、上記のよう
な現状に鑑みてなされたものであり、本発明の目的は、
このβ-フルオロ-α-ケト酸部分の原料ブロックとして
安価なβ,β,β-トリフルオロ乳酸を用いることによ
り、簡便に種々のβ-フルオロ-α-ケト酸及びその等価
体を製造する新しい方法を提供することにある。SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and the object of the present invention is to:
By using inexpensive β, β, β-trifluorolactic acid as a raw material block of this β-fluoro-α-keto acid moiety, various β-fluoro-α-keto acids and their equivalents can be easily produced. To provide a method.
【0007】[0007]
【課題を解決するための手段】本発明は、下記一般式化
3The present invention provides the following general formula 3
【化3】 (式中Xは水酸基保護基を、R’はカルボン酸保護のた
めのアルキル基を示す)で表されるトリフルオロ乳酸誘
導体に有機金属試薬を反応させることからなる下記一般
式化4[Chemical 3] (Wherein X represents a hydroxyl-protecting group and R ′ represents an alkyl group for protecting a carboxylic acid), a trifluorolactic acid derivative represented by the following general formula 4
【化4】 (式中Rは有機金属試薬由来のアルキル基を示し、X、
R’は上記と同じ)で表されるβ-フルオロ-α-ケト酸
等価体の製造方法で、特に好ましくは、前記有機金属試
薬として有機銅試薬を用いることからなるものである。[Chemical 4] (In the formula, R represents an alkyl group derived from an organometallic reagent, X,
R ′ is the same as the above), and a method for producing a β-fluoro-α-keto acid equivalent is particularly preferable, which comprises using an organocopper reagent as the organometallic reagent.
【0008】本発明の出発原料である上記一般式化3で
表わされるトリフルオロ乳酸誘導体としては、3,3,3
-トリフルオロ-2-(メタンスルホニルオキシ)プロピオ
ン酸メチル、3,3,3-トリフルオロ-2-(メタンスルホ
ニルオキシ)プロピオン酸エチル、3,3,3-トリフルオ
ロ-2-(メタンスルホニルオキシ)プロピオン酸イソプロ
ピル、3,3,3-トリフルオロ-2-(メタンスルホニルオ
キシ)プロピオン酸-l-メンチル、3,3,3-トリフルオ
ロ-2-(p-トルエンスルホニルオキシ)プロピオン酸メチ
ル、3,3,3-トリフルオロ-2-(p-トルエンスルホニル
オキシ)プロピオン酸エチル、3,3,3-トリフルオロ-
2-(p-トルエンスルホニルオキシ)プロピオン酸イソプ
ロピル、3,3,3-トリフルオロ-2-(p-トルエンスルホ
ニルオキシ)プロピオン酸-l-メンチル等を例示でき
る。The trifluorolactic acid derivative represented by the above general formula 3, which is the starting material of the present invention, is 3,3,3
Methyl -trifluoro-2- (methanesulfonyloxy) propionate Ethyl 3,3,3-trifluoro-2- (methanesulfonyloxy) propionate 3,3,3-Trifluoro-2- (methanesulfonyloxy) ) Isopropyl propionate, 3,3,3-trifluoro-2- (methanesulfonyloxy) propionate-l-menthyl methyl 3,3,3-trifluoro-2- (p-toluenesulfonyloxy) propionate, Ethyl 3,3,3-trifluoro-2- (p-toluenesulfonyloxy) propionate 3,3,3-trifluoro-
Examples include isopropyl 2- (p-toluenesulfonyloxy) propionate, 3,3,3-trifluoro-2- (p-toluenesulfonyloxy) propionic acid-1-menthyl and the like.
【0009】これらのトリフルオロ乳酸誘導体は、トリ
フルオロプロペンを微生物酸化することにより得られる
3,3,3-トリフルオロプロペンオキシド(特公昭61-
14798公報参照)を酸化することにより容易に得ら
れる3,3,3-トリフルオロ乳酸(特願平3-06097
9号、特願平3-103630号)のカルボキシル基を、
アルコールと硫酸触媒などの存在下でエステル化するこ
とにより保護した後、残っているその水酸基を酸塩化物
を用いて、酸エステル化することにより得られる。この
場合のカルボキシル基の保護に用いられるアルコールと
しては、メタノール、エタノール、プロパノール、ブタ
ノール、ヘキサノール、オクタノール等の1級アルコー
ル類、イソプロパノール、s-ブタノール、メンチルア
ルコール等2級アルコール、t-ブタノール等の3級ア
ルコールを用いることができ、このアルコールに特に制
限はなく、最後に脱保護するときの反応性、あるいは生
成物の取扱い易さを基準に最適のものを選ぶと良い。ま
た、水酸基の保護に用いられる酸塩化物は、同じく多種
多様なものを用い得るが、この反応の、エノールエステ
ル製造段階において分解、変性しないものであり、かつ
必要に応じて容易に脱保護できるものが好ましい、具体
的にはp-トルエンスルホン酸塩化物などのスルホン酸
塩化物が好適である。These trifluorolactic acid derivatives are 3,3,3-trifluoropropene oxide obtained by microbial oxidation of trifluoropropene (Japanese Examined Patent Publication No. 61-
14798), the 3,3,3-trifluorolactic acid easily obtained by oxidation (Japanese Patent Application No. 3-06097).
No. 9, Japanese Patent Application No. 3-103630),
After protected by esterification in the presence of an alcohol and a sulfuric acid catalyst or the like, the remaining hydroxyl group is acid-esterified with an acid chloride. Examples of the alcohol used for protecting the carboxyl group in this case include primary alcohols such as methanol, ethanol, propanol, butanol, hexanol, and octanol, secondary alcohols such as isopropanol, s-butanol, and menthyl alcohol, and t-butanol. A tertiary alcohol can be used, and the alcohol is not particularly limited, and it is advisable to select the most suitable alcohol based on the reactivity at the final deprotection or the ease of handling the product. A wide variety of acid chlorides can be used for the protection of hydroxyl groups, but they are not decomposed or modified in the enol ester production step of this reaction, and can be easily deprotected as necessary. Those which are preferable, specifically, sulfonic acid chlorides such as p-toluenesulfonic acid chloride are suitable.
【0010】本発明は、このようなトリフルオロ乳酸誘
導体に対して、有機金属試薬を作用させることにより上
記一般式化4で表されるエノールエステルを製造するも
のである。The present invention produces an enol ester represented by the above general formula 4 by reacting such a trifluorolactic acid derivative with an organometallic reagent.
【0011】本発明に用いられる有機金属試薬として
は、有機リチウム試薬、有機マグネシウム試薬、有機ア
ルミニウム試薬、有機銅試薬などを例示できるが、反応
性、反応選択性を考慮すれば、有機銅試薬が最適であ
る。この有機銅試薬も、その生成法により、いろいろな
種類があるが、一般に良く用いられる1価のハロゲン化
銅にグリニャール試薬を作用させて作る反応性の高いノ
ルマン氏型有機銅試薬を用いるとより良い結果を得るこ
とができ、特に好ましい。これらの有機金属試薬は、上
記原料のトリフルオロ乳酸誘導体1モルに対し2〜5モ
ル用いるとよい。Examples of the organometallic reagent used in the present invention include organolithium reagents, organomagnesium reagents, organoaluminum reagents, organocopper reagents and the like. Considering the reactivity and reaction selectivity, the organocopper reagents are Optimal. There are various types of this organocopper reagent depending on its production method, but it is more preferable to use a highly reactive Norman-type organocopper reagent prepared by reacting a commonly used monovalent copper halide with a Grignard reagent. Good results can be obtained, which is particularly preferable. These organometallic reagents may be used in an amount of 2 to 5 mol per 1 mol of the above-mentioned raw material trifluorolactic acid derivative.
【0012】反応は溶媒中で行い、この溶媒としては、
有機金属試薬の安定性上エーテル系の溶媒、特にはテト
ラヒドロフラン(THF)が好ましい。The reaction is carried out in a solvent.
An ether solvent, particularly tetrahydrofuran (THF), is preferable for the stability of the organometallic reagent.
【0013】反応温度については、有機金属試薬を添加
混合する時点までは、試薬の安定性上、室温以下の温度
で行い、添加し、十分に混合が行われたら加熱して反応
を進めると良い。反応の終了は、通常の分析手段などに
より原料物質が消費されたことを確認して決定すること
ができる。この反応は十分に速く、数時間以内に完結す
る。Regarding the reaction temperature, until the time of adding and mixing the organometallic reagent, it is advisable to carry out the reaction at a temperature of room temperature or lower for the stability of the reagent, and when the addition is completed and sufficient mixing is carried out, the reaction is heated. .. The completion of the reaction can be determined by confirming that the raw material has been consumed by an ordinary analytical means. The reaction is fast enough to complete within hours.
【0014】以上のようにして得られる反応混合物は、
塩酸などの酸により分解した後、有機溶媒による抽出、
乾燥、精製など通常の後処理により単離される。The reaction mixture obtained as described above is
After decomposing with acid such as hydrochloric acid, extraction with organic solvent,
It is isolated by a usual post-treatment such as drying and purification.
【0015】このようにして得られた上記一般式化4で
表されるエノールエステル化合物は、そのエノール位の
水酸基の保護をはずすことにより容易にエノール=ケト
互変異性化を起こし、下記一般式化5The thus obtained enol ester compound represented by the above general formula 4 easily undergoes enol = keto tautomerization by removing the protection of the hydroxyl group at the enol position, and the following general formula Conversion 5
【化5】 (式中R、R’は上記と同じ)で表されるβ-フルオロ-
α-ケト酸に変換することが可能である。[Chemical 5] (Wherein R and R ′ are the same as above), β-fluoro-
It is possible to convert to α-keto acid.
【0016】このエステル結合の分解条件等は、エノー
ル位の水酸基保護に用いた保護試薬により異なるが、種
々の試薬に応じた最適の方法が既に報告されている
〔[T.W.Greene, "Protective Groups in Organic Synth
esis" John Willy & Sons,(1981)〕。Although the conditions for decomposing the ester bond and the like differ depending on the protective reagent used for protecting the hydroxyl group at the enol position, the optimal method according to various reagents has already been reported [[TW Greene, "Protective Groups in Organic Synth
esis "John Willy & Sons, (1981)].
【0017】[0017]
【実施例】実施例1 〔3-フルオロ-3-フェニル-2-(p-トルエンスルホニル
オキシ)アクリル酸エチルの製造〕 ヨウ化銅0.54g
(3mmol)のTHF懸濁溶液にフェニルマグネシウムブロ
ミド(3mmol)を加え、30分の撹拌の後、3,3,3-ト
リフルオロ-2-(p-トルエンスルホニルオキシ)プロピオ
ン酸エチル0.33g(1mmol)のTHF溶液を滴下し、加
熱還流を2時間行った。EXAMPLES Example 1 [Production of ethyl 3-fluoro-3-phenyl-2- (p-toluenesulfonyloxy) acrylate] 0.54 g of copper iodide
Phenylmagnesium bromide (3 mmol) was added to a THF suspension solution of (3 mmol), and after stirring for 30 minutes, ethyl 3,3,3-trifluoro-2- (p-toluenesulfonyloxy) propionate 0.33 g ( A THF solution (1 mmol) was added dropwise, and the mixture was heated under reflux for 2 hours.
【0018】反応溶液は砕いた氷の上にあけ、3%の塩
酸を加えて、エーテル抽出を行った。硫酸マグネシウム
で乾燥した後、溶媒を減圧留去し、カラムクロマトグラ
フィーによって分離精製し、さらに再結晶法による精製
を行い、収率67%で、次の物性を有する3-フルオロ-
3-フェニル-2-(p-トルエンスルホニルオキシ)アクリ
ル酸エチルを得た。 融点:71〜73℃1 H-NMR(CCl4)δ:1.12(t,3H)、2.43(s,3H)、4.
03(q,2H)、7.25(q,2H)、7.35(s,5H)、7.80
(d,2H) ppm.19 F-NMR(CCl4)δ:7.23(s) ppm. IR(KBr):1725、1370、1600、1650 cm
-1. MS(M+(m/e)):362The reaction solution was poured onto crushed ice, 3% hydrochloric acid was added, and the mixture was extracted with ether. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, the residue was separated and purified by column chromatography, and further purified by a recrystallization method. The yield was 67%, and 3-fluoro- had the following physical properties.
Ethyl 3-phenyl-2- (p-toluenesulfonyloxy) acrylate was obtained. Melting point: 71-73 ° C 1 H-NMR (CCl 4 ) δ: 1.12 (t, 3H), 2.43 (s, 3H), 4.
03 (q, 2H), 7.25 (q, 2H), 7.35 (s, 5H), 7.80
(d, 2H) ppm. 19 F-NMR (CCl 4 ) δ: 7.23 (s) ppm. IR (KBr): 1725, 1370, 1600, 1650 cm
-1 .MS (M + (m / e)): 362
【0019】実施例2 〔3-フルオロ-3-メチル-2-(p-トルエンスルホニルオ
キシ)アクリル酸エチルの製造〕 ヨウ化銅1.80g(9mmol)のTHF懸濁溶液にメチルマ
グネシウムブロミド(9mmol)を加え、30分の撹拌の
後、3,3,3-トリフルオロ-2-(p-トルエンスルホニル
オキシ)プロピオン酸エチル0.98g(3mmol)のTHF
溶液を滴下し、一晩撹拌した。反応溶液は砕いた氷の上
にあけ、3%の塩酸を加えてエーテル抽出を行った。硫
酸マグネシウムで乾燥後、溶媒を減圧留去し、カラムク
ロマトグラフィ-によって分離精製し、収率71%で次
の物性を有する3-フルオロ-3-メチル-2-(p-トルエン
スルホニルオキシ)アクリル酸エチルを得た。1 H-NMR(CCl4)δ:1.15(t,3H)、2.35(d,3H)、2.
40(s,3H)、4.02(q,2H)、7.21(d,2H)、7.67
(d,2H) ppm.19 F-NMR(CCl4)δ:2.10(q) ppm. IR(KBr):1720、1670、1600、1380、
1450cm-1. MS(M+(m/e)):302 Example 2 [Production of ethyl 3-fluoro-3-methyl-2- (p-toluenesulfonyloxy) acrylate] Methyl magnesium bromide (9 mmol) was added to a THF suspension solution of 1.80 g (9 mmol) of copper iodide. ) Was added and after stirring for 30 minutes, ethyl 3,3,3-trifluoro-2- (p-toluenesulfonyloxy) propionate 0.98 g (3 mmol) of THF was added.
The solution was added dropwise and stirred overnight. The reaction solution was placed on crushed ice and 3% hydrochloric acid was added to perform ether extraction. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was separated and purified by column chromatography to give 3-fluoro-3-methyl-2- (p-toluenesulfonyloxy) acrylic acid having the following physical properties in a yield of 71%. Obtained ethyl. 1 H-NMR (CCl 4 ) δ: 1.15 (t, 3H), 2.35 (d, 3H), 2.
40 (s, 3H), 4.02 (q, 2H), 7.21 (d, 2H), 7.67
(d, 2H) ppm. 19 F-NMR (CCl 4 ) δ: 2.10 (q) ppm. IR (KBr): 1720, 1670, 1600, 1380,
1450cm -1 .MS (M + (m / e)): 302
【0020】実施例3 〔3-フルオロ-3-メチル-2-(p-トルエンスルホニルオ
キシ)アクリル酸-l-メンチルの製造〕 ヨウ化銅1.80g(9mmol)のTHF懸濁溶液にメチルマ
グネシウムブロミド(9mmol)を加え、30分撹拌の後、
3,3,3-トリフルオロ-2-(p-トルエンスルホニルオキ
シ)プロピオン酸-l-メンチル1.30g(3mmol)のTH
F溶液を滴下し、一晩撹拌した。反応溶液は砕いた氷の
上にあけ、3%の塩酸を加えてエーテル抽出を行った。
硫酸マグネシウムで乾燥した後、溶媒を減圧留去し、カ
ラムクロマトグラフィーによって分離精製し、収率63
%で次の物性を有する3-フルオロ-3-メチル-2-(p-ト
ルエンスルホニルオキシ)アクリル酸-l-メンチルを得
た。1 H-NMR(CCl4)δ:0.40〜2.13(m,18H)、2.38
(d,3H)、2.42(s,3H)、4.29〜4.99(br,1H)、
7.21(d,2H)、7.71(d,2H) ppm.19 F-NMR(CCl4)δ:1.70(d) ppm. IR(KBr):1720、1670、1600、1380、
1450cm-1. MS(M+(m/e)):412 Example 3 [Production of 3-fluoro-3-methyl-2- (p-toluenesulfonyloxy) acrylic acid-1-menthyl] Methylmagnesium was added to a THF suspension solution of 1.80 g (9 mmol) of copper iodide. Bromide (9 mmol) was added and after stirring for 30 minutes,
1,3,3,3-trifluoro-2- (p-toluenesulfonyloxy) propionic acid-1-menthyl 1.30 g (3 mmol) of TH
The F solution was added dropwise and stirred overnight. The reaction solution was placed on crushed ice and 3% hydrochloric acid was added to perform ether extraction.
After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography to give a yield of 63.
% 3-fluoro-3-methyl-2- (p-toluenesulfonyloxy) acrylic acid-1-menthyl having the following physical properties was obtained. 1 H-NMR (CCl 4 ) δ: 0.40 to 2.13 (m, 18H), 2.38
(d, 3H), 2.42 (s, 3H), 4.29 to 4.99 (br, 1H),
7.21 (d, 2H), 7.71 (d, 2H) ppm. 19 F-NMR (CCl 4 ) δ: 1.70 (d) ppm. IR (KBr): 1720, 1670, 1600, 1380,
1450cm -1 .MS (M + (m / e)): 412
【0021】[0021]
【発明の効果】本発明は、産業上有用な含フッ素原料化
合物である種々のβ-フルオロ-α-ケト酸等価体を簡便
かつ安価に製造することができ、これにより、従来入手
することが難しかった、或いは不可能であったβ-フル
オロ-α-ケト酸あるいはその等価体を安価に入手するこ
とができるようになり、このβ-フルオロ-α-ケト酸あ
るいはその等価体化合物を原料とする生理活性物質など
を安価に製造できるようになる。Industrial Applicability According to the present invention, various β-fluoro-α-keto acid equivalents, which are industrially useful fluorine-containing raw material compounds, can be produced simply and inexpensively, and thus can be obtained conventionally. The difficult or impossible β-fluoro-α-keto acid or its equivalent became available at low cost, and this β-fluoro-α-keto acid or its equivalent compound was used as a raw material. It becomes possible to inexpensively produce a physiologically active substance or the like.
Claims (2)
めのアルキル基を示す)で表されるトリフルオロ乳酸誘
導体に有機金属試薬を反応させることを特徴とする下記
一般式化2 【化2】 (式中Rはアルキル基を示し、X、R’は上記と同じ)
で表されるβ-フルオロ-α-ケト酸等価体の製造方法。1. The following general formula 1 (Wherein X represents a hydroxyl-protecting group and R ′ represents an alkyl group for protecting a carboxylic acid) and a trifluorolactic acid derivative represented by the following general formula: Chemical 2] (In the formula, R represents an alkyl group, and X and R ′ are the same as above)
A method for producing a β-fluoro-α-keto acid equivalent represented by:
薬であることを特徴とするβ-フルオロ-α-ケト酸等価
体を製造する方法。 【0001】2. A method for producing a β-fluoro-α-keto acid equivalent, wherein the organometallic reagent according to claim 1 is an organocopper reagent. [0001]
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP3244246A JPH0558955A (en) | 1991-08-30 | 1991-08-30 | Production of beta-fluoro-alpha-keto acid equivalent substance |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP3244246A JPH0558955A (en) | 1991-08-30 | 1991-08-30 | Production of beta-fluoro-alpha-keto acid equivalent substance |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH0558955A true JPH0558955A (en) | 1993-03-09 |
Family
ID=17115907
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP3244246A Pending JPH0558955A (en) | 1991-08-30 | 1991-08-30 | Production of beta-fluoro-alpha-keto acid equivalent substance |
Country Status (1)
Country | Link |
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JP (1) | JPH0558955A (en) |
Cited By (5)
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---|---|---|---|---|
KR100401958B1 (en) * | 2000-12-29 | 2003-10-17 | 주식회사 태평양 | Enol form compounds of alpha-keto carboxylates derivatives and method for preparing thereof |
WO2005105963A1 (en) * | 2004-05-04 | 2005-11-10 | Yki, Ytkemiska Institutet Ab | Decomposing surfactant |
US7160925B2 (en) | 2004-05-04 | 2007-01-09 | Yki, Ytkemiska Institutet Ab | Decomposing surfactant |
US8991829B2 (en) | 2007-11-20 | 2015-03-31 | The Timken Company | Non-contact labyrinth seal assembly and method of construction thereof |
CN109633071A (en) * | 2019-02-27 | 2019-04-16 | 贵州健安德科技有限公司 | A method of utilizing the gloomy copper of thiophene in UPLC-MS/MS method detection water |
-
1991
- 1991-08-30 JP JP3244246A patent/JPH0558955A/en active Pending
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100401958B1 (en) * | 2000-12-29 | 2003-10-17 | 주식회사 태평양 | Enol form compounds of alpha-keto carboxylates derivatives and method for preparing thereof |
WO2005105963A1 (en) * | 2004-05-04 | 2005-11-10 | Yki, Ytkemiska Institutet Ab | Decomposing surfactant |
US7160925B2 (en) | 2004-05-04 | 2007-01-09 | Yki, Ytkemiska Institutet Ab | Decomposing surfactant |
US8991829B2 (en) | 2007-11-20 | 2015-03-31 | The Timken Company | Non-contact labyrinth seal assembly and method of construction thereof |
US9291272B2 (en) | 2007-11-20 | 2016-03-22 | Federal-Mogul Corporation | Non-contact labyrinth seal assembly and method of construction thereof |
CN109633071A (en) * | 2019-02-27 | 2019-04-16 | 贵州健安德科技有限公司 | A method of utilizing the gloomy copper of thiophene in UPLC-MS/MS method detection water |
CN109633071B (en) * | 2019-02-27 | 2021-05-07 | 贵州健安德科技有限公司 | Method for detecting Saisentong copper in water by using UPLC-MS/MS method |
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