JP2020007282A - Method for producing fluoroalkylpyridine - Google Patents

Abstract

To provide a method for producing a fluoroalkylpyridine that can use highly safe raw materials and allows a fluoroalkylpyridine to be prepared simply in one stage reaction step.SOLUTION: A method for producing a fluoroalkylpyridine includes preparing a fluoroalkylpyridine represented by the following formula by reacting, in the presence of a base, a propiolic acid ester having a specific structure and an aminocrotonate having a specific structure (Ris a C1-10 alkyl group, Ris one or more F-substituted C1-10 alkyl group).SELECTED DRAWING: None

Description

  The present invention relates to a method for producing a fluoroalkylpyridine, for example, a method for producing a fluoroalkylpyridine by reacting a propiolate and an aminocrotonate to obtain a fluoroalkylpyridine.

  Fluoroalkylpyridines are important as intermediates for medical and agricultural chemicals, and are used for synthesizing various physiologically active substances. For example, various reports have been made on the reaction, pharmacological activity, and use of 6-hydroxy-2-trifluoromethylpyridine-3-carboxylate.

As a method for producing a fluoroalkylpyridine, a production method using acrylamide as a raw material (see Patent Documents 1 to 4) and a production method using acryloyl chloride have been proposed (see Patent Document 5). In any of these production methods, in the first-stage reaction, a cycloaddition reaction between acrylamide or acryloyl chloride, which is a raw material, and an ester compound is performed. Next, in the second-stage reaction, an oxidation reaction of the cycloaddition product is performed to obtain a fluoroalkylpyridine (for example, 6-hydroxy-2-trifluoromethylpyridine-3-carboxylate). .
In the production method of Patent Document 1, the yield of the first-stage cycloaddition product is 9%, and the second-stage final product (6-hydroxy-2-trifluoromethylpyridine-3-carboxylic acid) is obtained. Ester) is 70%, and the total yield of 6-hydroxy-2-trifluoromethylpyridine-3-carboxylate is 6.3%.
In the production methods of Patent Documents 2 to 4, the yield of the first-stage cycloaddition product is 25%, and the second-stage final product (6-hydroxy-2-trifluoromethylpyridine-3- The carboxylic acid ester) yield was 92%, and the total yield of 6-hydroxy-2-trifluoromethylpyridine-3-carboxylic acid ester was 23%.
Further, in the production method of Patent Document 5, the yield of the first-stage cycloaddition product is 35%, and the second-stage oxidation reaction is carried out without isolating the cycloaddition product. Therefore, the total yield of the final product fluoroalkylpyridine is not described.

  On the other hand, as another method for producing a fluoroalkylpyridine, a method of first synthesizing a non-fluorinated alkylpyridine and then producing a fluoroalkylpyridine by a fluorination reaction has been proposed (Patent Documents 6 to 10). reference). Regarding the production of alkylpyridines, the methods described in Patent Documents 6 to 9 include performing an addition reaction between a propiolate ester and an aminocrotonate ester in a first step, and then performing a cyclization reaction in a second step. Gives alkylpyridine. However, Patent Document 6 does not mention the position of the double bond in the first-stage adduct. In Patent Document 9, the yield of the first-stage adduct is 93%, the yield of the second-stage cyclization reaction is 60%, and the total yield of alkylpyridine is 56%. It is stated that there is. Subsequently, with respect to the production of fluoroalkylpyridine by the fluorination reaction of alkylpyridine, according to the method described in Patent Document 10, 2-methylpyridine is oxidized with chlorine gas in the presence of anhydrous hydrogen fluoride to form 2-tripyridine. It is stated that fluoromethylpyridine is obtained.

International Publication No. 2011/020615 International Publication No. 2005/074939 International Publication No. 2004/029027 International Publication No. 2004/029026 US Patent Application Publication No. 2009/0247588 WO 2006/028958 International Publication No. 2008/085119 International Publication No. 2009/126863 WO 2013/056015 JP-A-57-9762

Org. Process Res. Dev. , 1 (1), 370, 1997

  In the synthesis of fluoroalkylpyridine using acrylamide as disclosed in Patent Documents 1 to 4, since strict safety measures are indispensable due to the high harmfulness of acrylamide, the operability, convenience, and economic efficiency in work are reduced. Becomes In addition, since fluoroalkylpyridines are mainly used as intermediates for pharmaceuticals and agricultural chemicals, the above-mentioned production method using a compound such as acrylamide, which is highly harmful, may be problematic from the viewpoint of reaction residues. Was. For this reason, strict removal steps and analysis steps for preventing acrylamide and the like from remaining in the product cannot be avoided.

  In the method for producing a fluoroalkylpyridine using acryloyl chloride as disclosed in Patent Document 5, acryloyl chloride, which is an acid chloride, is easily hydrolyzed by moisture in the air such as moisture, and generates heat and corrosive hydrogen chloride. May emit smoke. Therefore, in a method for producing a fluoroalkylpyridine using acryloyl chloride, a strictly anhydrous environment and corrosion-resistant equipment may be required. In addition, acryloyl chloride is more unstable to heat and light than acrylamide and causes a polymerization reaction very easily. Therefore, addition of a polymerization inhibitor is indispensable in handling. Therefore, when acryloyl chloride is used, an operation of adding a polymerization inhibitor to a raw material and removing the polymerization inhibitor from a product is required, which is inefficient.

  In addition, in the production methods of fluoroalkylpyridine using acrylamide or acryloyl chloride described in Patent Documents 1 to 5, a cycloaddition product as an intermediate (for example, 6-hydroxy-2-trifluoromethyl-4) , 5-dihydropyridine-3-carboxylic acid ester). In this oxidation step, N-bromosuccinimide (NBS) used as an oxidizing agent was low in atomic efficiency, harmful to carbon tetrachloride used as a solvent, and high in environmental load. In addition, these reactions are susceptible to impurities and the yield of the final product is not stable, and there is a problem that excessive oxidation competes as a side reaction (see Non-Patent Document 1).

  Further, in the methods described in Patent Documents 6 to 9, after an adduct of a propiolate and an aminocrotonate is obtained in a first-stage reaction, the adduct is cyclized in a second-stage reaction. It was necessary to form a pyridine ring, and the operation was complicated and inefficient due to the two-step reaction. Furthermore, the second stage cyclization reaction had to be carried out at a high temperature because the progress of the reaction was difficult. Therefore, in the methods of Patent Documents 6 to 9, the reaction is carried out by heating to at least 160 ° C., and a large amount of energy needs to be input. In addition, Patent Document 6 requires an operation of adding a strongly basic reagent, and Patent Documents 7 and 8 require microwave heating equipment.

  The method described in Patent Document 10 uses a gaseous reactant such as chlorine or anhydrous hydrogen fluoride as a gas phase reaction. Since these reactants are gases having extremely high toxicity and corrosiveness, handling involves great danger and strict safety management is indispensable. Further, in Patent Document 10, since the progress of the reaction is slow, not only heating to about 400 ° C. is necessary, but also a by-product in which a plurality of chlorines are introduced on an aromatic ring is mixed in the product. It is described. For this reason, the method of Patent Literature 10 has a problem that energy efficiency, selectivity, and functional group tolerance are low. Due to these restrictions, it can be determined that the method of first obtaining alkylpyridine by the methods described in Patent Documents 6 to 9 and then converting it to fluoroalkylpyridine by the method described in Patent Document 10 is not suitable for practical use.

  The present invention has been made in view of such circumstances. That is, the present inventor studied a raw material of fluoroalkylpyridine that can be substituted for acrylamide and acryloyl chloride. As a result, they have found that propiolate and aminocrotonate having a specific structure are useful as raw materials and can solve the above-mentioned problems. That is, propiolate is less harmful to the human body than acrylamide and, unlike acryloyl chloride, does not generate heat, smoke, or hydrolyze in contact with water, and does not cause a vigorous polymerization reaction. In addition, in the reaction with propiolate, fluoroaminocrotonate, unlike aminocrotonate, gives a fluoroalkylpyridine in one step, so there is no need to provide an additional oxidation reaction step, and the intermediate intermediate can be used alone. Loss due to separation and purification and excess reaction can also be avoided. As a result, the present inventors have found that fluoroalkylpyridine can be easily obtained in a one-step reaction process, and have completed the present invention.

  That is, an object of the present invention is to provide a method for producing a fluoroalkylpyridine, which can use a highly safe raw material and can easily obtain a fluoroalkylpyridine in a one-step reaction process.

一般式（２）

一般式（３）

（上記一般式（１）〜（３）において、Ｒ_１及びＲ_２はそれぞれ独立して炭素数１以上１０以下のアルキル基を表し、Ｒ_３は１以上のフッ素原子で置換された炭素数１以上１０以下のアルキル基を表す。）
［２］前記塩基が、１、５−ジアザビシクロ−［４．３．０］−ノネン、１，８−ジアザビシクロ−［５，４，０］−７−ウンデセン、メチルトリアザビシクロデセン、およびジアザビシクロオクタンからなる群から選択された少なくとも１種の塩基である、上記［１］に記載のフルオロアルキルピリジンの製造方法。
［３］上記一般式（１）で表されるプロピオール酸エステルと、上記一般式（２）で表されるアミノクロトン酸エステルとを、０〜６０℃で反応させる、上記［１］または［２］に記載のフルオロアルキルピリジンの製造方法。
［４］前記プロピオール酸エステルが、下記式（４）で表される、上記［１］から［３］までのいずれか１つに記載のフルオロアルキルピリジンの製造方法。
式（４）

［５］前記Ｒ_３は、炭素数１以上１０以下のパーフルオロアルキル基である、上記［１］から［４］までのいずれか１つに記載のフルオロアルキルピリジンの製造方法。
［６］前記アミノクロトン酸エステルが下記式（５）で表される、上記［１］から［５］までのいずれか１つに記載のフルオロアルキルピリジンの製造方法。
式（５）

The gist configuration of the present invention is as follows.
[1] In the presence of a base, a propiolic acid ester represented by the following general formula (1) is reacted with an amino crotonic acid ester represented by the following general formula (2) to give the following general formula (3) A method for producing a fluoroalkylpyridine, which obtains a fluoroalkylpyridine represented by the formula:
General formula (1)

General formula (2)

General formula (3)

(In the above general formulas (1) to (3), R ₁ and R ₂ each independently represent an alkyl group having 1 to 10 carbon atoms, and R ₃ has 1 carbon atom substituted by one or more fluorine atoms. Represents an alkyl group of 10 or more and 10 or less.)
[2] The base is 1,5-diazabicyclo- [4.3.0] -nonene, 1,8-diazabicyclo- [5,4,0] -7-undecene, methyltriazabicyclodecene, and diaza The method for producing a fluoroalkylpyridine according to the above [1], wherein the base is at least one kind of base selected from the group consisting of bicyclooctane.
[3] The above [1] or [2], wherein the propiolate represented by the general formula (1) and the aminocrotonate represented by the general formula (2) are reacted at 0 to 60 ° C. ] The method for producing a fluoroalkylpyridine according to [1].
[4] The method for producing a fluoroalkylpyridine according to any one of the above [1] to [3], wherein the propiolate is represented by the following formula (4).
Equation (4)

[5] The method for producing a fluoroalkylpyridine according to any one of [1] to [4], wherein R ₃ is a perfluoroalkyl group having 1 to 10 carbon atoms.
[6] The method for producing a fluoroalkylpyridine according to any one of [1] to [5], wherein the aminocrotonate is represented by the following formula (5).
Equation (5)

  It is possible to provide a method for producing a fluoroalkylpyridine, which can use a highly safe raw material and can easily obtain a fluoroalkylpyridine in a one-step reaction process.

FIG. 1 is a view showing the results of gas chromatography analysis of the product obtained in Example 1. FIG. 2 is a diagram showing the results of mass spectrometry of the product obtained in Example 1.

  Hereinafter, embodiments of the present invention will be described in detail. Note that the present invention is not limited by the following embodiments.

一般式（２）

一般式（３）

（上記一般式（１）〜（３）において、Ｒ_１及びＲ_２はそれぞれ独立して炭素数１以上１０以下のアルキル基を表し、Ｒ_３は１以上のフッ素原子で置換された炭素数１以上１０以下のアルキル基を表す。）。 In one embodiment of the method for producing a fluoroalkylpyridine, a propiolic acid ester represented by the following general formula (1) and an amino crotonic acid ester represented by the following general formula (2) are reacted in the presence of a base. The reaction is performed to obtain a fluoroalkylpyridine represented by the following general formula (3).
General formula (1)

General formula (2)

General formula (3)

(In the above general formulas (1) to (3), R ₁ and R ₂ each independently represent an alkyl group having 1 to 10 carbon atoms, and R ₃ has 1 carbon atom substituted by one or more fluorine atoms. And represents an alkyl group of 10 or more).

（なお、上記反応式（６）において、置換基Ｒ_１〜Ｒ_３は、上記一般式（１）〜（３）の置換基Ｒ_１〜Ｒ_３と同義である。）
すなわち、上記式（６）で表されるように、プロピオール酸エステルと、アミノクロトン酸エステルとから環状のピリジン構造が形成されると共に、プロピオール酸エステルに由来するＲ_１ＯＨが生成する。 One example of the above reaction is represented by the following formula (6).
Equation (6)

(In the above reaction formula (6), the substituents _R 1 to R ₃ have the same meanings as the substituents _R 1 to R ₃ in formula (1) to (3).)
That is, as represented by the above formula (6), a cyclic pyridine structure is formed from the propiolate and the aminocrotonate, and R ₁ OH derived from the propiolate is generated.

In one embodiment of the method for producing a fluoroalkylpyridine, a propiolate is used as a raw material. Therefore, unlike the conventional method, there is no need to use acrylamide which is harmful to the human body, and there is no need to use acryloyl chloride which generates heat, emits smoke and hydrolyzes in contact with water. Since the propiolic acid ester is an oxidized form of acrylic acid, the production method of one embodiment does not require an oxidation reaction step, and a fluoroalkylpyridine can be obtained in one step, and the reaction step is simplified to provide an intermediate. Loss due to isolation and purification and excess reaction can be avoided.
In addition, in a conventional method for producing an alkylpyridine using an acrylic acid derivative as a raw material, a polymer of the acrylic acid derivative can be formed. Since the polymer of the acrylic acid derivative is stabilized by releasing enormous energy when the main chain is polymerized into a saturated hydrocarbon chain, the reaction system may be heated to a high temperature or may explode. On the other hand, propiolate used as a raw material in the production method of one embodiment hardly forms a polymer, and even when a polymer is formed, its main chain becomes an unsaturated hydrocarbon chain. Contributes little to the stabilization, and reduces the amount of heat generated during polymerization. As a result, a chain polymerization reaction hardly occurs, and safety is improved.
Therefore, in one embodiment, not only the reduction of waste, the simplification of the reaction process, the improvement of the work efficiency and the improvement of economy can be realized, but also a highly safe raw material can be used, and the one-stage reaction process can be simplified. It is possible to realize a method for producing a fluoroalkylpyridine, which can obtain a fluoroalkylpyridine.

R ₁ in the general formula (1) is not particularly limited as long as it is an alkyl group having 1 to 10 carbon atoms, but is preferably an alkyl group having 1 to 5 carbon atoms, and is preferably an alkyl group having 1 to 3 carbon atoms. More preferred. More specifically, R ₁ is a methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group or n-pentyl group. Preferably, a methyl group, an ethyl group, an n-propyl group or an i-propyl group is more preferable, and a methyl group is more preferable.

R ₂ in the general formulas (2) to (3) is not particularly limited as long as it is an alkyl group having 1 to 10 carbon atoms, but is preferably an alkyl group having 1 to 5 carbon atoms, and 1 to 3 carbon atoms. Is more preferred. More specifically, R ₂ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an s-butyl group, an i-butyl group, a t-butyl group or an n-pentyl group. Preferably, a methyl group, an ethyl group, an n-propyl group or an i-propyl group is more preferable, and an ethyl group is further more preferable.

R ₃ in the above general formulas (2) to (3) is not particularly limited as long as it is an alkyl group having 1 to 10 carbon atoms and substituted with one or more fluorine atoms, but is substituted with one or more fluorine atoms. An alkyl group having 1 to 5 carbon atoms is preferable, and an alkyl group having 1 to 3 carbon atoms and substituted with one or more fluorine atoms is more preferable. Further, in R ₃ , the number of fluorine atoms substituting the alkyl group is not particularly limited as long as it is 1 or more, but the number of carbon atoms of 1 to 10 in which all hydrogen atoms in the alkyl group have been substituted with fluorine atoms. Preferably it is a fluoroalkyl group. More specifically, a perfluoromethyl group, a perfluoroethyl group, a perfluoropropyl group, a perfluorobutyl group, and a perfluoropentyl group are preferable, and a perfluoromethyl group, a perfluoroethyl group, and a perfluoropropyl group are more preferable. And a perfluoromethyl group (trifluoromethyl group) is more preferred.

アミノクロトン酸エステルは、下記式（５）で表されるアミノクロトン酸エステルであることが特に好ましい。
式（５）

The propiolate is particularly preferably a propiolate represented by the following formula (4).
Equation (4)

The amino crotonic acid ester is particularly preferably an amino crotonic acid ester represented by the following formula (5).
Equation (5)

（上記一般式（７）において、Ｒ_２は炭素数１以上１０以下のアルキル基を表す。）。 It is particularly preferable to produce 6-hydroxy-2-trifluoromethylpyridine-3-carboxylic acid ester represented by the following general formula (7) as a fluoroalkylpyridine.
General formula (7)

(In the general formula (7), R ₂ represents an alkyl group having 1 to 10 carbon atoms.)

  In one embodiment of the method for producing a fluoroalkylpyridine, the reaction between the propiolate and the aminocrotonate is carried out in the presence of a base. Examples of the base used in the above reaction include 1,5-diazabicyclo- [4.3.0] -nonene (DBN) and 1,8-diazabicyclo- [5,4,0] -7-undecene (DBU). And organic nitrogen derivatives such as methyltriazabicyclodecene and diazabicyclooctane, and a phosphazene base. The amount of the base to be used is preferably (propiolic ester) :( base) = 1: 0.1 to 5, more preferably 1: 0.2 to 3, and 1: 0.5 to 1.5 in a molar ratio. More preferred.

  In the method for producing a fluoroalkylpyridine according to one embodiment, the reaction can be efficiently performed, and therefore, the reaction temperature can be set preferably low. The propiolate represented by the general formula (1) and the aminocrotonate represented by the general formula (2) are preferably reacted at 0 to 100 ° C, and are reacted at 0 to 80 ° C. More preferably, the reaction is more preferably performed at 0 to 60 ° C.

  The reaction time between the propiolate and the aminocrotonate is preferably from 30 minutes to 72 hours, more preferably from 1 hour to 48 hours, even more preferably from 2 hours to 36 hours.

  Examples of the solvent for reacting the propiolate and the aminocrotonate include, for example, tetrahydrofuran (THF), monoglyme, diglyme, triglyme, tetraglyme, dioxane, acetonitrile, dimethylformamide, dimethylacetamide, methylpyrrolidone, dimethylethyleneurea, An aprotic polar solvent such as dimethylpropylene urea, tetramethyl urea, dimethyl sulfoxide, and sulfolane is used.

  In one embodiment of the method for producing a fluoroalkylpyridine, the aminocrotonate is preferably added in an excess molar equivalent to the propiolate. Thereby, the anion polymerization reaction between the base used in the reaction and the propiolate represented by the above general formula (1) can be suppressed, and the yield of fluoroalkylpyridine is improved. The use ratio (molar ratio) of propiolate to aminocrotonate (propiolate) :( aminocrotonate) is more than 1: 1 and 5 or less, preferably 1: 1.3-3. More preferably, 1: 1.5-2.5 is even more preferable.

  In one embodiment of the method for producing a fluoroalkylpyridine, it is preferable to add an aminocrotonate to a solution in which a base is dissolved, and then add a propiolate to the solution. This can suppress an anionic polymerization reaction between the base used in the reaction and the propiolate, thereby improving the yield of fluoroalkylpyridine.

  After the fluoroalkylpyridine obtained by the production method of one embodiment is dried over anhydrous sodium sulfate and filtered, the formation of the fluoroalkylpyridine can be confirmed by GC-MS.

As described above, in the method for producing a fluoroalkylpyridine according to one embodiment, since a propiolate is used as a raw material, it is not necessary to use acrylamide which is harmful to the human body. Further, it is possible to obtain a fluoroalkylpyridine without using acryloyl chloride which generates heat, emits smoke and hydrolyzes in contact with water as a raw material. In the production method of one embodiment, since the propiolic acid ester as the raw material is an oxidized form of acrylic acid, the fluoroalkylpyridine can be obtained in one step without requiring an oxidation reaction step, and the reaction step is simplified. Loss due to isolation and purification of intermediates and excess reaction can also be avoided.
In addition, in a conventional method for producing an alkylpyridine using an acrylic acid derivative as a raw material, a polymer of the acrylic acid derivative can be formed. Since the polymer of the acrylic acid derivative is stabilized by releasing a huge amount of energy when the main chain is polymerized to become a saturated hydrocarbon chain, the reaction system may be heated to a high temperature or may explode. On the other hand, propiolate used as a raw material in the production method of one embodiment hardly forms a polymer, and even when a polymer is formed, its main chain becomes an unsaturated hydrocarbon chain. The contribution of stabilization is small, and the calorific value during polymerization decreases. As a result, a chain polymerization reaction hardly occurs, and safety is improved.
Thus, according to the method for producing a fluoroalkylpyridine of the above embodiment, not only can the reduction of waste, the simplification of the reaction process, the improvement of work efficiency and the improvement of economy be realized, but also a highly safe raw material Can be used, and a fluoroalkylpyridine production method capable of easily obtaining a fluoroalkylpyridine in a one-step reaction process can be realized.

In the production method of the fluoroalkyl pyridine embodiment, one of the causes that generate the reaction of simplified manner fluoroalkyl pyridine occurs in one step, R ₃ in the amino crotonic acid ester used as the raw material is a fluorine atom It is considered to have. That is, since a fluorine atom has high electronegativity, R ₃ is an electron-withdrawing substituent. Then, an intermediate between propiolate and aminocrotonate, which is an intermediate of the reaction for producing fluoroalkylpyridine from propiolate and aminocrotonate, was provided by a base during cyclization. It is considered that the electrons are passing through a negatively charged carbanion. Here, since R ₃ contained in the transition-state carbanion is an electron-withdrawing group, it is presumed that the carbanion is stabilized by attracting a negative charge in the carbanion. As a result, it is considered that the activation energy of a series of reactions is reduced, and fluoroalkylpyridine can be easily generated. Also, the greater the number of fluorine atoms bonded to one carbon atom, the electron-withdrawing R ₃ increases, when R ₃ is a perfluoroalkyl group, fluoroalkyl pyridine as the most easily generated Presumed.

  Hereinafter, the present invention will be described in more detail with reference to examples. In addition, this invention is not limited at all by the following Examples.

(Example 1)
In a 100 mL three-necked flask, 6.25 g of tetrahydrofuran (THF), 25 g (136 mmol) of ethyl 3-amino-4,4,4-trifluorocrotonate, and diazabicyclo- [5,4,0] -7-undecene (DBU). 11.5 g (75.5 mmol) were added with stirring. Next, under cooling with ice water, 6.25 g (74.3 mmol) of methyl propiolate was added dropwise so that the internal temperature did not exceed 20 ° C, and the mixture was stirred for 1 hour, and then heated to 60 ° C. After stirring for 24 hours, the content was separated, dried and filtered with anhydrous sodium sulfate, and then subjected to GC-MS (model number: QP2010, manufactured by Shimadzu Corporation, column: DB-1MS, manufactured by Agilent Technologies, Inc.). Moving layer: analyzed by He). The results are shown in FIGS. 1 and 2, it was confirmed that ethyl 6-hydroxy-2-trifluoromethylpyridine-3-carboxylate was obtained.

Claims (6)

In the presence of a base, a propiolic acid ester represented by the following general formula (1) is reacted with an amino crotonic acid ester represented by the following general formula (2) to be represented by the following general formula (3). A process for producing a fluoroalkylpyridine.
General formula (1)

General formula (2)

General formula (3)

(In the above general formulas (1) to (3), R ₁ and R ₂ each independently represent an alkyl group having 1 to 10 carbon atoms, and R ₃ has 1 carbon atom substituted by one or more fluorine atoms. Represents an alkyl group of 10 or more and 10 or less.)   The base is from 1,5-diazabicyclo- [4.3.0] -nonene, 1,8-diazabicyclo- [5,4,0] -7-undecene, methyltriazabicyclodecene, and diazabicyclooctane. The method for producing a fluoroalkylpyridine according to claim 1, which is at least one base selected from the group consisting of:   The fluoroalkyl according to claim 1, wherein the propiolate represented by the general formula (1) and the aminocrotonate represented by the general formula (2) are reacted at 0 to 60 ° C. 4. Method for producing pyridine. The method for producing a fluoroalkylpyridine according to any one of claims 1 to 3, wherein the propiolate is represented by the following formula (4).
Equation (4)

Wherein R ₃ is a perfluoroalkyl group having 1 to 10 carbon atoms, the production method of fluoroalkyl pyridine according to any one of claims 1 to 4. The method for producing a fluoroalkylpyridine according to any one of claims 1 to 5, wherein the aminocrotonate is represented by the following formula (5).
Equation (5)

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