JP4067847B2 - Method for producing 1-alkoxy-2-fluoro-3-hydroxy compound by nucleophilic ring-opening fluorination to 1-alkoxy-2,3 epoxy compound - Google Patents
Method for producing 1-alkoxy-2-fluoro-3-hydroxy compound by nucleophilic ring-opening fluorination to 1-alkoxy-2,3 epoxy compound Download PDFInfo
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- JP4067847B2 JP4067847B2 JP2002070883A JP2002070883A JP4067847B2 JP 4067847 B2 JP4067847 B2 JP 4067847B2 JP 2002070883 A JP2002070883 A JP 2002070883A JP 2002070883 A JP2002070883 A JP 2002070883A JP 4067847 B2 JP4067847 B2 JP 4067847B2
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- APIUVWCYNNMEPM-UHFFFAOYSA-N NC1OC1CO Chemical compound NC1OC1CO APIUVWCYNNMEPM-UHFFFAOYSA-N 0.000 description 1
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Description
【０００１】
【発明の属する技術分野】
本発明は、新規フッ素化剤および１−アルコキシ−２，３−エポキシ化合物の求核的開環フッ素化反応への利用に関する。
【０００２】
【従来の技術】
エポキシ化合物の開環フッ素化において、フッ素化剤の選択は重要な問題である。フッ素化剤としてフッ化水素を単独で用いると、操作性が悪く危険である上、重合が進行してしまう場合があり、目的物は得られない。また、三フッ素ホウ素を用いた場合は、転移反応が進行してしまい、位置および立体的制御が難しい。
【０００３】
特に、２，３−エポキシアルコール類の求核的フッ素化開環は、位置および立体化学制御が難しく、幾つかのフッ素化剤が試されているが、従来法のほとんどが、Ｃ−３位選択的なフッ素化であった。例えばTetrahedron Lett.,1990,31(49),7209-7212（フッ素化剤：K2HF2／H2F3NBu4）、J.Org.Chem.,1988,53,1026-1030（フッ素化剤：ジイソプロピルアミントリハイドロフルオライド）Tetrahedoron Lett.,1992,33,(47),7083-7086(フッ素化剤：(HF)2/NBu4F）、Tetrahedoron Lett.,1992,33,(47),7087-7088(フッ素化剤：(RO)4-nTiFn）の合成例が示されているが、いずれもＣ−３位にフッ素が結合した化合物が主成分として生成する。唯一、J.Org.Chem.,1988,53,1026-1030に記載されている合成例でフッ素化剤としてピリジンポリハイドロフルオライドを用いた場合においてＣ−２位とＣ−３位が同等の割合で生成しているが、Ｃ−２選択的な生成物を与える合成例は、これまで報告されていない。
【０００４】
【発明が解決しようする課題】
本発明は、１−アルコキシ−２，３−エポキシ化合物の開環フッ素化において、Ｃ−２位選択的フッ素化を進行させるようなフッ素化剤およびその利用法の提供を目的とする。
【０００５】
【問題を解決するための手段】
本発明者は上記の課題を解決すべく鋭意検討した結果、フッ化水素酸アンモニウム塩と４族遷移金属フッ化物塩とからなるフッ素化剤が、１−アルコキシ−２，３−エポキシ化合物に対し、Ｃ−２位選択的に開環フッ素化することを見出し、本発明に至った。
【０００６】
すなわち、本発明は、一般式［１］
【０００７】
【化４】
［式中、ＲはＣ1-10の直鎖あるいは分岐アルキル基を表す］で示されるフッ化水素酸アンモニウム塩と４族遷移金属フッ化物塩とからなるフッ素化剤である。
【０００９】
また、本発明は、４族遷移金属フッ化物塩がチタン、ジルコニウム、ハフニウムの金属フッ化物である上記に記載のフッ素化剤である。
【００１０】
また、本発明は、 一般式［２］
【００１１】
【化５】
［式中、Ｒ1およびＲ2は水素、Ｃ1-10置換または無置換の飽和または不飽和の直鎖または分岐アルキル基、Ｃ3-8環状アルキル基、無置換もしくは置換アリール基、無置換もしくは置換ヘテロ環を表し、同一でも異なっていてもよい］で示される１−アルコキシ−２，３−エポキシ化合物に上記に記載のフッ素化剤を作用させて開環フッ素化し、一般式［３］
【００１３】
【化６】
［式中、Ｒ1およびＲ2は一般式［２］と同じ］で示される１−アルコキシ−２−フルオロ−３−ヒドロキシロ化合物を製造する方法である。
【００１５】
【発明の実施の形態】
本発明に用いるフッ素化剤は、フッ化水素酸アンモニウム塩と４族遷移金属フッ化物塩を室温で混合することにより調製できる。フッ化水素酸アンモニウム塩は、一般式［１］に示すようなアンモニウム４級塩で、テトラアルキルアンモニウム ジハイドロジェントリフルオライド類（Ｈ2Ｆ3ＮＲ4）である。
【００１６】
ここで、ＲはＣ1-10の直鎖あるいは分岐のアルキル基を示す。具体的には、直鎖アルキル基として、メチル、エチル、プロピル、ブチル、ペンチル、ヘキシル、ヘプチル、オクチル、デシル等を、また分岐アルキル基として、イソプロピル、ｓｅｃ−ブチル、ｔｅｒｔ−ブチル、２−メチルブチル、イソペンチル、イソヘキシル、３−エチルオクチル、等を示すことができる。
【００１７】
また、４属遷移金属フッ化物塩は、チタン、ジルコニウム、ハフニウムの金属フッ化物であり、具体的には、四フッ化チタン、三フッ化チタン、四フッ化ジルコニウム、四フッ化ハフニウムを挙げることができ、特に四フッ化ジルコニウム、四フッ化ハフニウムが好ましい。
【００１８】
使用されるフッ化水素酸アンモニウム塩の量は４属遷移金属フッ化物塩１モルに対して、０．５〜２．０モルで、好ましくは０．８〜１．２モルである。
【００１９】
本発明のフッ素化反応においては、一般式［２］で示される１−アルコキシ−２，３−エポキシ化合物を原料とし、上記フッ素化剤を作用させて開環フッ素化することにより、Ｃ−２選択的なフッ素化を進行させ、一般式［３］に示すような、１−アルコキシ−２−フルオロ−３−ヒドロキシ化合物を製造することができる。
【００２０】
本発明における１−アルコキシ−２，３−エポキシ化合物において、Ｒ1およびＲ2は水素、Ｃ1-10置換または無置換の飽和または不飽和の鎖状または分岐アルキル基、Ｃ3-8環状アルキル基、無置換もしくは置換アリール基、無置換もしくは置換ヘテロ環を表し、同一でも異なっていてもよい。
【００２１】
具体的には、メチル、エチル、プロピル、ブチル、ペンチル、ヘキシル、ヘプチル、オクチル、デシル等のＣ1-10の直鎖飽和アルキル、イソプロピル、ｓｅｃ−ブチル、ｔｅｒｔ−ブチル、２−メチルブチル、イソペンチル、イソヘキシル、３−エチルオクチル等のＣ1-10等の飽和分岐アルキル、ビニル、プロペニル、ブテニル、ペンテニル、ヘキセニル、デセニル、２−プロペニル、１−メチル−１−プロペニル、１−エチル−１−ブテニル、２，４−ジメチル−１−ペンテニル、２，４−ジメチル−２−ペンテニル基等のＣ2-10の直鎖または分岐アルケニル基、シクロプロピル、シクロヘキシル、シクロオクチル等のＣ3-8環状アルキル基等が挙げられる。 また、アリール基としては、フェニル基、ヘテロ環としては、ピロリジン環、ピペリジン環、、イミダゾリジン環、イミダゾリジノン環、ピリミジン環、ピリミジノン環が挙げられる。
【００２２】
これらは置換されていてもよく、ここで置換基としては本発明の方法において不活性な置換基であればよいが、アルキル基、アルケニル基、アルキニル基にあっては、アリール基、ヘテロ環式基、アルコキシ基、三級アミノ基等であり、また、アーリル基、ヘテロ環式基にあっては、アルキル基、アルケニル基、アルキニル基、アリール基、ヘテロ環式基、アルコキシ基、三級アミノ基等である。
【００２３】
本発明のフッ素化反応に用いられるフッ素化剤の量は、通常、一般式［２］で示される１−アルコキシ−２，３−エポキシ化合物に対して、１モル当量以上使用すればよく、１〜１０モル当量が好ましく、特に１〜５モル当量が好ましい。
【００２４】
本発明のフッ素化に用いられる反応溶媒は、原料の１−アルコキシ−２，３−エポキシ化合物および生成物である１−アルコキシ−２−フルオロ−３−ヒドロキシ化合物と反応しないものであれば特に限定されないが、例えば、アセトニトリル、プロピオニトリル、ブチロニトリルのようなニトリル系、ベンゼン、トルエン、キシレン、塩化ベンゼン等の芳香族類、ジエチルエーテル、イソプロピルエーテル、ジブチルエーテル、テトラヒドロフラン、１，４−ジオキサン等のエーテル類、四塩化炭素、クロロホルム、ジクロロメタン等のハロゲン化炭化水素類が挙げられる。その中でも、アセトニトリル、トルエン、塩化ベンゼン、テトラヒドロフラン、ジクロロメタンが好ましく、特にテトラヒドロフラン、ジクロロメタンがより好ましい。これらの溶媒は、単独または組み合わせて使用することができる。また、溶媒量は原料の１−アルコキシ−２，３−エポキシ化合物が溶解する範囲内であればよく、使用原料量の１倍以上用いれば良い。
【００２５】
本反応のフッ素化の反応温度は、室温付近で容易に反応が進行する。当然のことながら、加熱下においては効率よく進行する。
【００２６】
本反応の後処理においては、通常の後処理操作を行うことにより粗生成物を得ることができる。得られた粗生成物は、必要に応じて、活性炭、蒸留、カラムクロマトグラフィー等の精製操作を行うことにより、目的の一般式［３］で示される１−アルコキシ−２−フルオロ−３−ヒドロキシ化合物を得ることができる。
【００２７】
【実施例】
以下実施例により本発明の実施の形態を具体的に説明するが、本発明はこれらの実施例に限定されるものではない。
【００２８】
「実施例１」
○フッ素化剤の調製
テトラブチルアンモニウム ジハイドロジェントリフルオライド（Ｈ2Ｆ3ＮＢｕ4）と四フッ化チタン（ＴｉＦ4）を等モル量混合し、室温で１０分間攪拌した。
○開環フッ素化反応
フッ素化剤調製溶液（塩化ベンゼン溶液、エポキシ化合物に対して二倍当量）に式［４］
【００２９】
【化７】
に示す１−ヒドロキシ−２，３−エポキシアルコールを滴下し、０℃で１時間攪拌後、室温で８時間攪拌した。反応は穏やかに進行し、式［５］
【００３１】
【化８】
に示す１，３ジヒドロキシ−２−フルオロ化合物（２−Ｆ体）をおよび式［６］
【００３３】
【化９】
に示す１，２−ジヒドロキシ−３−フルオロ化合物（３−Ｆ体）を得た。19Ｆ−ＮＭＲで確認したところ、２−Ｆ体と３−Ｆ体を合わせた収率は８６％で、２−Ｆ体と３−Ｆ体との比は６６：３４であった。
【００３５】
「実施例２〜実施例３」
実施例１と同じ系で、フッ素化剤調製時の４属遷移金属フッ化物塩として四フッ化チタン（ＴｉＦ4）を用い、開環フッ素化反応時の溶媒の種類、反応時間を変えて、室温において、実施例１と同様な操作を行った。結果を実施例１の結果と合わせて表１に示した。
【００３６】
「実施例４〜実施例５」
実施例１と同じ系で、フッ素化剤調製時の４属遷移金属フッ化物塩として三フッ化チタン（ＴｉＦ3）を用い、開環フッ素化反応時の溶媒の種類、反応時間を変えて、室温において、実施例１と同様な操作を行った。結果を表１に示した。
【００３７】
「実施例６〜実施例７」
実施例１と同じ系で、フッ素化剤調製時の４属遷移金属フッ化物塩として四フッ化ジルコニウム（ＺｒＦ4）を用い、開環フッ素化反応時の溶媒の種類、反応時間を変えて、室温において、実施例１と同様な操作を行った。結果を表１に示した。
【００３８】
「実施例８〜実施例９」
実施例１と同じ系で、フッ素化剤調製時の４属遷移金属フッ化物塩として四フッ化ハフニウム（ＨｆＦ4）を用い、開環フッ素化反応時の溶媒の種類、反応時間を変えて、室温において、実施例１と同様な操作を行った。結果を表１に示した。
【００３９】
「参考例１」
実施例１と同じ系で、塩化ベンゼン中、フッ素化剤としてテトラブチルアンモニウム ジハイドロジェントリフルオライド（Ｈ2Ｆ3ＮＢｕ4）のみを使用し、１４０℃で２０時間反応させ、開環フッ素化を行った。２−Ｆ体と３−Ｆ体を合わせた収率は６０％で、２−Ｆ体と３−Ｆ体との比は３９：６１であった。結果を表１に示した。
【００４０】
【表１】
【発明の効果】
１−アルコキシ−２，３−エポキシ化合物の開環フッ素化において、Ｃ−２位選択的フッ素化生成物を与えるフッ素化剤を簡単な操作で製造できる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel fluorinating agent and use of 1-alkoxy-2,3-epoxy compounds for nucleophilic ring-opening fluorination reactions.
[0002]
[Prior art]
In the ring-opening fluorination of epoxy compounds, the selection of the fluorinating agent is an important issue. When hydrogen fluoride is used alone as the fluorinating agent, the operability is poor and dangerous, and the polymerization may proceed, and the target product cannot be obtained. In addition, when boron trifluoride is used, the transfer reaction proceeds and position and steric control are difficult.
[0003]
In particular, the nucleophilic fluorinated ring-opening of 2,3-epoxy alcohols is difficult to control the position and stereochemistry, and several fluorinating agents have been tried. It was selective fluorination. For example, Tetrahedron Lett., 1990, 31 (49), 7209-7212 (fluorinating agent: K 2 HF 2 / H 2 F 3 NBu 4 ), J. Org. Chem., 1988, 53, 1026-1030 (fluorination) Agent: Diisopropylamine trihydrofluoride) Tetrahedoron Lett., 1992, 33, (47), 7083-7086 (fluorinating agent: (HF) 2 / NBu 4 F), Tetrahedoron Lett., 1992, 33, (47) , 7087-7088 (fluorinating agent: (RO) 4-n TiF n ) are shown as examples, but in each case, a compound in which fluorine is bonded to the C-3 position is generated as a main component. Only in the synthesis example described in J. Org. Chem., 1988, 53, 1026-1030, when pyridine polyhydrofluoride is used as the fluorinating agent, the C-2 position and the C-3 position are equivalent. No synthetic examples have been reported so far that produce in proportion but give C-2 selective products.
[0004]
[Problems to be solved by the invention]
An object of the present invention is to provide a fluorinating agent that allows selective C-2 fluorination to proceed in ring-opening fluorination of a 1-alkoxy-2,3-epoxy compound and a method for using the fluorinating agent.
[0005]
[Means for solving problems]
As a result of intensive studies to solve the above problems, the present inventor has found that a fluorinating agent comprising an ammonium hydrofluoric acid salt and a Group 4 transition metal fluoride salt has a 1-alkoxy-2,3-epoxy compound. , C-2 position-selective ring-opening fluorination was found, and the present invention was reached.
[0006]
That is, the present invention relates to the general formula [1]
[0007]
[Formula 4]
[Wherein, R represents a C 1-10 linear or branched alkyl group] is a fluorinating agent comprising an ammonium hydrofluoride salt and a Group 4 transition metal fluoride salt.
[0009]
Moreover, this invention is a fluorinating agent as described in the above, wherein the group 4 transition metal fluoride salt is a metal fluoride of titanium, zirconium, or hafnium.
[0010]
The present invention also provides a general formula [2]
[0011]
[Chemical formula 5]
[Wherein R 1 and R 2 are hydrogen, C 1-10 substituted or unsubstituted saturated or unsaturated linear or branched alkyl group, C 3-8 cyclic alkyl group, unsubstituted or substituted aryl group, unsubstituted Or a substituted heterocycle, which may be the same or different], and the fluorinating agent described above is allowed to act on the 1-alkoxy-2,3-epoxy compound represented by formula (3).
[0013]
[Chemical 6]
[In the formula, R 1 and R 2 are the same as those in the general formula [2]] A method for producing a 1-alkoxy-2-fluoro-3-hydroxy compound represented by the general formula [2].
[0015]
DETAILED DESCRIPTION OF THE INVENTION
The fluorinating agent used in the present invention can be prepared by mixing ammonium hydrofluoric acid salt and Group 4 transition metal fluoride salt at room temperature. The ammonium hydrofluoric acid salt is a quaternary ammonium salt represented by the general formula [1] and is a tetraalkylammonium dihydrofluoride (H 2 F 3 NR 4 ).
[0016]
Here, R represents a C 1-10 linear or branched alkyl group. Specifically, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, decyl, etc. are used as linear alkyl groups, and isopropyl, sec-butyl, tert-butyl, 2-methylbutyl are used as branched alkyl groups. , Isopentyl, isohexyl, 3-ethyloctyl, and the like.
[0017]
The Group 4 transition metal fluoride salt is a metal fluoride of titanium, zirconium, or hafnium, and specifically includes titanium tetrafluoride, titanium trifluoride, zirconium tetrafluoride, or hafnium tetrafluoride. In particular, zirconium tetrafluoride and hafnium tetrafluoride are preferable.
[0018]
The amount of ammonium hydrofluoride used is 0.5 to 2.0 moles, preferably 0.8 to 1.2 moles per mole of Group 4 transition metal fluoride salt.
[0019]
In the fluorination reaction of the present invention, a 1-alkoxy-2,3-epoxy compound represented by the general formula [2] is used as a raw material, and the above fluorinating agent is allowed to act on the ring-opening fluorination to produce C-2. Selective fluorination proceeds to produce a 1-alkoxy-2-fluoro-3-hydroxy compound as represented by the general formula [3].
[0020]
In the 1-alkoxy-2,3-epoxy compound of the present invention, R 1 and R 2 are hydrogen, C 1-10 substituted or unsubstituted saturated or unsaturated chain or branched alkyl group, C 3-8 cyclic alkyl Represents a group, an unsubstituted or substituted aryl group, an unsubstituted or substituted heterocycle, which may be the same or different.
[0021]
Specifically, C 1-10 linear saturated alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, decyl, isopropyl, sec-butyl, tert-butyl, 2-methylbutyl, isopentyl, isohexyl, saturated branched alkyl of C 1-10 such as 3-ethyl-octyl, vinyl, propenyl, butenyl, pentenyl, hexenyl, decenyl, 2-propenyl, 1-methyl-1-propenyl, 1-ethyl-1-butenyl, C 2-10 linear or branched alkenyl groups such as 2,4-dimethyl-1-pentenyl and 2,4-dimethyl-2-pentenyl groups, and C 3-8 cyclic alkyl groups such as cyclopropyl, cyclohexyl and cyclooctyl Etc. Examples of the aryl group include a phenyl group, and examples of the heterocycle include a pyrrolidine ring, a piperidine ring, an imidazolidine ring, an imidazolidinone ring, a pyrimidine ring, and a pyrimidinone ring.
[0022]
These may be substituted, and the substituent may be any substituent that is inactive in the method of the present invention. However, in the case of an alkyl group, alkenyl group, or alkynyl group, an aryl group, a heterocyclic group may be used. Group, alkoxy group, tertiary amino group and the like, and in the case of aryl group and heterocyclic group, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, alkoxy group, tertiary amino group, etc. Group.
[0023]
The amount of the fluorinating agent used in the fluorination reaction of the present invention is usually 1 molar equivalent or more with respect to the 1-alkoxy-2,3-epoxy compound represented by the general formula [2]. 10 to 10 molar equivalents are preferable, and 1 to 5 molar equivalents are particularly preferable.
[0024]
The reaction solvent used in the fluorination of the present invention is not particularly limited as long as it does not react with the raw material 1-alkoxy-2,3-epoxy compound and the product 1-alkoxy-2-fluoro-3-hydroxy compound. For example, nitriles such as acetonitrile, propionitrile, butyronitrile, aromatics such as benzene, toluene, xylene, benzene chloride, diethyl ether, isopropyl ether, dibutyl ether, tetrahydrofuran, 1,4-dioxane, etc. And halogenated hydrocarbons such as ethers, carbon tetrachloride, chloroform, and dichloromethane. Among these, acetonitrile, toluene, benzene chloride, tetrahydrofuran, and dichloromethane are preferable, and tetrahydrofuran and dichloromethane are more preferable. These solvents can be used alone or in combination. Moreover, the amount of solvent should just be in the range which 1-alkoxy-2,3-epoxy compound of a raw material melt | dissolves, and should just use 1 time or more of the amount of raw materials to be used.
[0025]
The reaction proceeds easily around the room temperature of the fluorination reaction of this reaction. As a matter of course, it proceeds efficiently under heating.
[0026]
In the post-treatment of this reaction, a crude product can be obtained by carrying out ordinary post-treatment operations. The obtained crude product is subjected to purification operations such as activated carbon, distillation, column chromatography, etc. as necessary to give 1-alkoxy-2-fluoro-3-hydroxy represented by the general formula [3]. A compound can be obtained.
[0027]
【Example】
The embodiments of the present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.
[0028]
"Example 1"
Preparation of fluorinating agent Tetrabutylammonium dihydrofluoride (H 2 F 3 NBu 4 ) and titanium tetrafluoride (TiF 4 ) were mixed in equimolar amounts and stirred at room temperature for 10 minutes.
○ Ring opening fluorination reaction Fluorinating agent preparation solution (chlorobenzene solution, double equivalent to epoxy compound) formula [4]
[0029]
[Chemical 7]
1-hydroxy-2,3-epoxy alcohol was added dropwise and stirred at 0 ° C. for 1 hour and then at room temperature for 8 hours. The reaction proceeds gently, with the formula [5]
[0031]
[Chemical 8]
And a 1,3-dihydroxy-2-fluoro compound (2-F form) represented by formula (6):
[0033]
[Chemical 9]
1,2-dihydroxy-3-fluoro compound (3-F form) was obtained. As confirmed by 19 F-NMR, the combined yield of 2-F and 3-F was 86%, and the ratio of 2-F to 3-F was 66:34.
[0035]
"Example 2 to Example 3"
In the same system as in Example 1, titanium tetrafluoride (TiF 4 ) was used as the Group 4 transition metal fluoride salt during preparation of the fluorinating agent, and the type of solvent and reaction time during the ring-opening fluorination reaction were changed. The same operation as in Example 1 was performed at room temperature. The results are shown in Table 1 together with the results of Example 1.
[0036]
"Example 4 to Example 5"
In the same system as in Example 1, using titanium trifluoride (TiF 3 ) as the Group 4 transition metal fluoride salt at the time of preparing the fluorinating agent, changing the type of solvent and the reaction time during the ring-opening fluorination reaction, The same operation as in Example 1 was performed at room temperature. The results are shown in Table 1.
[0037]
"Example 6 to Example 7"
In the same system as in Example 1, zirconium tetrafluoride (ZrF 4 ) was used as the Group 4 transition metal fluoride salt during preparation of the fluorinating agent, and the solvent type and reaction time during the ring-opening fluorination reaction were changed. The same operation as in Example 1 was performed at room temperature. The results are shown in Table 1.
[0038]
"Example 8 to Example 9"
In the same system as in Example 1, using hafnium tetrafluoride (HfF 4 ) as the Group 4 transition metal fluoride salt during preparation of the fluorinating agent, changing the type of solvent and the reaction time during the ring-opening fluorination reaction, The same operation as in Example 1 was performed at room temperature. The results are shown in Table 1.
[0039]
"Reference Example 1"
In the same system as in Example 1, using only tetrabutylammonium dihydrofluoride (H 2 F 3 NBu 4 ) as a fluorinating agent in chlorobenzene, the reaction is carried out at 140 ° C. for 20 hours to effect ring-opening fluorination. went. The combined yield of 2-F form and 3-F form was 60%, and the ratio of 2-F form and 3-F form was 39:61. The results are shown in Table 1.
[0040]
[Table 1]
【The invention's effect】
In ring-opening fluorination of 1-alkoxy-2,3-epoxy compounds, a fluorinating agent that gives a C-2 position selective fluorination product can be produced by a simple operation.
Claims (3)
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| JP2002070883A JP4067847B2 (en) | 2001-03-14 | 2002-03-14 | Method for producing 1-alkoxy-2-fluoro-3-hydroxy compound by nucleophilic ring-opening fluorination to 1-alkoxy-2,3 epoxy compound |
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| JP2002070883A JP4067847B2 (en) | 2001-03-14 | 2002-03-14 | Method for producing 1-alkoxy-2-fluoro-3-hydroxy compound by nucleophilic ring-opening fluorination to 1-alkoxy-2,3 epoxy compound |
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