JP7375519B2 - Method for producing halogenated acrylic acid ester - Google Patents

Description

The present invention relates to a method for producing a halogenated acrylic ester and a synthetic intermediate thereof.

Halogenated acrylic esters, especially α-fluoroacrylic esters, are used as monomers in optical materials such as optical fiber sheath materials, intermediates for paints, intermediates for semiconductor resist materials, and pharmaceutical synthesis intermediates. It is useful as such.

The method for producing α-fluoroacrylic acid ester is to react methyl α-fluoroacetate with oxalic acid in the presence of sodium methoxide, react the generated enol sodium salt intermediate with paraformaldehyde, and produce α-fluoroacrylate. Method for producing methyl acid (Patent Document 1);
A method for producing methyl α-fluoroacrylate by reacting a 1-fluoroethene derivative with carbon monoxide and methanol in the presence of a transition metal catalyst and a base is known (Patent Document 2).

The method of Patent Document 1 is difficult to handle and cannot be carried out safely due to the high toxicity of methyl α-fluoroacetate. Furthermore, since it is a two-step reaction, it cannot be called a simple method.
The method of Patent Document 2 is difficult to handle and cannot be carried out safely due to the high toxicity of carbon monoxide. Furthermore, the reaction is carried out in an autoclave, which is hardly a method suitable for industrial production.

CN 102211998A WO 2014/034906 A1

An object of the present invention is to provide a method for producing halogenated acrylic esters in a safe and simple manner that is suitable for industrial production without using highly toxic raw materials.

As a result of intensive studies to solve the above problems, the present inventors found that a route using a compound represented by the following formula (1), which is easily available and has low toxicity, is a safe and simple method. discovered that halogenated acrylic esters can be produced by a method suitable for industrial production, and completed the present invention.

That is, the present invention is as follows.
[1]
A step of reacting a compound represented by formula (1) (hereinafter also referred to as compound (1)) with a compound represented by formula (2) (hereinafter also referred to as compound (2)) in the presence of a base. A method for producing a compound represented by formula (4) (hereinafter also referred to as compound (4)), characterized in that:

[In the formula,
X ¹ , X ² and X ³ each independently represent a halogen atom,
Y represents a halogen atom,
R represents a C _1-8 alkyl group, a C _3-8 cycloalkyl group, a C _7-14 aralkyl group or a C _6-10 aryl group,
Here, the C _1-8 alkyl group is a halogen atom, a cyano group, a C _1-4 alkoxy group, a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group. , optionally substituted with a group selected from an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group,
The C _3-8 cycloalkyl group, C _7-14 aralkyl group and C _6-10 aryl group are halogen atoms, cyano groups, C _1-4 alkyl groups, C _1-4 haloalkyl groups, and C _1-4 alkoxy groups. , a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group, an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group. Each may be substituted with a group. ]
[2]
The manufacturing method described in [1] above, wherein the reaction is performed in a reaction system containing water.
[3]
The production method described in [1] or [2] above, wherein the reaction is performed in a solvent containing water.
[4]
The manufacturing method described in [1] or [2] above, wherein water is added during the reaction.
[5]
The production method according to any one of [1] to [4] above, wherein the base is an alkali metal C _1-4 alkoxide.
[6]
The manufacturing method according to the above [5], wherein R in formula (2) is a C _1-4 alkyl group, and the base is RONa or ROK, which is used in the form of an ROH solution.
[7]
The production method according to any one of [1] to [4] above, wherein the base is an alkali metal hydroxide and is used in the form of an aqueous solution.
[8]
The production method according to any one of [1] to [7] above, wherein the reaction is carried out within the range of 30 to 180°C.
[9]
The manufacturing method according to any one of [1] to [8] above, wherein Y is a fluorine atom.
[10]
The production method according to any one of [1] to [9] above, wherein R is a C _1-2 alkyl group.
[11]
The manufacturing method according to any one of [1] to [10] above, wherein X ² and X ³ are both fluorine atoms.
[12]
The manufacturing method according to any one of [1] to [11] above, wherein X ¹ is a fluorine atom.

[13]
A compound represented by formula (3) (hereinafter also referred to as compound (3)) is produced by reacting a compound represented by formula (1) with a compound represented by formula (2) in the presence of a base. method of manufacturing

[In the formula,
X ¹ , X ² and X ³ each independently represent a halogen atom,
Y represents a halogen atom,
R represents a C _1-8 alkyl group, a C _3-8 cycloalkyl group, a C _7-14 aralkyl group or a C _6-10 aryl group,
Here, the C _1-8 alkyl group is a halogen atom, a cyano group, a C _1-4 alkoxy group, a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group. , optionally substituted with a group selected from an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group,
The C _3-8 cycloalkyl group, C _7-14 aralkyl group and C _6-10 aryl group are halogen atoms, cyano groups, C _1-4 alkyl groups, C _1-4 haloalkyl groups, and C _1-4 alkoxy groups. , a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group, an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group. Each may be substituted with a group. ]

[14]
A method for producing a compound represented by formula (4), which comprises reacting a compound represented by formula (3) in the presence of water.

[In the formula,
X ² and X ³ each independently represent a halogen atom,
Y represents a halogen atom,
R represents a C _1-8 alkyl group, a C _3-8 cycloalkyl group, a C _7-14 aralkyl group or a C _6-10 aryl group,
Here, the C _1-8 alkyl group is a halogen atom, a cyano group, a C _1-4 alkoxy group, a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group. , optionally substituted with a group selected from an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group,
The C _3-8 cycloalkyl group, C _7-14 aralkyl group and C _6-10 aryl group are halogen atoms, cyano groups, C _1-4 alkyl groups, C _1-4 haloalkyl groups, and C _1-4 alkoxy groups. , a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group, an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group. Each may be substituted with a group. ]

[15]
A compound represented by formula (1) is reacted with a compound represented by formula (2) in the presence of a base, and then the resulting reaction mixture is reacted in the presence of water. 4) A method for producing the compound represented by.

[In the formula,
X ¹ , X ² and X ³ each independently represent a halogen atom,
Y represents a halogen atom,
R represents a C _1-8 alkyl group, a C _3-8 cycloalkyl group, a C _7-14 aralkyl group or a C _6-10 aryl group,
Here, the C _1-8 alkyl group is a halogen atom, a cyano group, a C _1-4 alkoxy group, a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group. , optionally substituted with a group selected from an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group,
The C _3-8 cycloalkyl group, C _7-14 aralkyl group and C _6-10 aryl group are halogen atoms, cyano groups, C _1-4 alkyl groups, C _1-4 haloalkyl groups, and C _1-4 alkoxy groups. , a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group, an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group. Each may be substituted with a group. ]

[16]
A compound represented by formula (3a).

[In the formula, X ² and X ³ each independently represent a halogen atom, Y represents a halogen atom, and R ^a represents a C _1-8 alkyl group. ]

According to the present invention, halogenated acrylic esters can be produced in a safe and simple manner, and in a manner suitable for industrial production, without using highly toxic raw materials.

Hereinafter, the definitions of groups used in this specification will be explained in detail. Unless otherwise specified, groups have the following definitions.

In this specification, the compound represented by the formula is indicated by adding the number of the formula to "compound". For example, the compound represented by formula (1) is referred to as "compound (1)."
In this specification, the numerical range represented by "~" or "-" means a numerical range in which the lower limit or upper limit is the number before or after the "~" or "-".
In this specification, when a numerical range is attached to the element symbol "C" by numbers before and after "-" and a numerical range is attached to the name of an arbitrary group, the numbers before and after "-" are used as the lower limit. Alternatively, each represents an arbitrary group having an integer number of carbon atoms as the upper limit. For example, an alkyl group having 1 to 3 carbon atoms is sometimes referred to as a "C _1-3 alkyl group," but this refers to each of -CH ₃ , -C ₂ H ₅ , -C ₃ H ₇ It shows. The same applies to other groups.

As used herein, the term "halogen atom" means a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

As used herein, the term "C _1-8 alkyl group" means a linear or branched saturated hydrocarbon group having 1 to 8 carbon atoms. Examples of "C _1-8 alkyl group" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1- Examples include dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, octyl, and C _1-4 alkyl groups are preferred.

As used herein, the term "C _1-4 alkyl group" means a linear or branched saturated hydrocarbon group having 1 to 4 carbon atoms. Examples of the "C _1-4 alkyl group" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, and tert-butyl, with a C _1-2 alkyl group being preferred.

As used herein, the term "C _1-2 alkyl group" means a linear or branched saturated hydrocarbon group having 1 to 2 carbon atoms. Examples of the "C _1-2 alkyl group" include methyl and ethyl, with methyl being preferred.

As used herein, the term "C _1-4 alkoxy group" means a group represented by the formula R ¹¹ O- (wherein R ¹¹ represents a C _1-4 alkyl group). Examples of the "C _1-4 alkoxy group" include methoxy, ethoxy, propoxy, isopropoxy, butyloxy, isobutyloxy, sec-butyloxy, and tert-butyloxy.

As used herein, the term "C _1-4 haloalkyl group" means a group in which one or more of the hydrogen atoms in the "C _1-4 alkyl group" is substituted with a halogen atom. Examples of the "C _1-4 haloalkyl group" include fluoromethyl, 2-fluoroethyl, 3-fluoropropyl, 4-fluorobutyl, trifluoromethyl, difluoromethyl, perfluoroethyl, perfluoropropyl, chloromethyl, 2-chloroethyl , bromomethyl, 2-bromoethyl, iodomethyl, 2-iodoethyl and the like, with trifluoromethyl being preferred.

As used herein, the term "C _1-4 haloalkoxy group" means a group in which one or more hydrogen atoms in the "C _1-4 alkoxy group" are substituted with a halogen atom. Examples of the "C _1-4 haloalkoxy group" include bromomethoxy, 2-bromoethoxy, 3-bromopropoxy, 4-bromobutoxy, iodomethoxy, 2-iodoethoxy, 3-iodopropoxy, 4-iodobutoxy, Fluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, tribromomethoxy, trichloromethoxy, trifluoromethoxy, difluoromethoxy, perfluoroethoxy, perfluoropropoxy, perfluoroisopropoxy, 1,1,2,2- Examples include tetrafluoroethoxy and 2-chloro-1,1,2-trifluoroethoxy.

As used herein, the term "C _3-8 cycloalkyl group" means a cyclic saturated hydrocarbon group having 3 to 8 carbon atoms. Examples of the "C _3-8 cycloalkyl group" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

As used herein, the term "C _6-10 aryl group" means a hydrocarbon group having 6 to 10 carbon atoms and having aromatic properties. Examples of the "C _6-10 aryl group" include phenyl, 1-naphthyl, and 2-naphthyl, with phenyl being preferred.

As used herein, the term "C _7-14 aralkyl group" means a "C _1-4 alkyl group" substituted with a "C _6-10 aryl group". Examples of the "C _7-14 aralkyl group" include benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, (1-naphthyl)methyl, (2-naphthyl)methyl, etc. , benzyl is preferred.

Examples of the protecting group for the "optionally protected amino group" include tert-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, acetyl, trifluoroacetyl, and the like.

Examples of the protecting group for the "optionally protected carboxy group" include methyl, ethyl, tert-butyl, benzyl and the like.

Protective groups for the "optionally protected hydroxy group" include benzyl, trityl, and the like.

Examples of the protecting group for the "optionally protected sulfanyl group" include methyl, ethyl, benzyl, trityl, and the like.

The definitions of each group in formulas (1) to (4) will be explained below.
X ¹ represents a halogen atom.
X ¹ is preferably a fluorine atom, a chlorine atom or a bromine atom, more preferably a fluorine atom or a chlorine atom, particularly preferably a fluorine atom.

X ² and X ³ each independently represent a halogen atom.
X ² and X ³ are preferably each independently a fluorine atom or a chlorine atom, particularly preferably both are fluorine atoms.

Y represents a halogen atom.
Y is preferably a fluorine atom.

R represents a C _1-8 alkyl group, a C _3-8 cycloalkyl group, a C _7-14 aralkyl group or a C _6-10 aryl group,
Here, the C _1-8 alkyl group is a halogen atom, a cyano group, a C _1-4 alkoxy group, a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group. , optionally substituted with a group selected from an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group,
The C _3-8 cycloalkyl group, C _7-14 aralkyl group and C _6-10 aryl group are halogen atoms, cyano groups, C _1-4 alkyl groups, C _1-4 haloalkyl groups, and C _1-4 alkoxy groups. , a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group, an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group. Each may be substituted with a group.
As a specific example of R,
Methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2,2- Trifluoroethyl, 3,3,3-trifluoropropyl, 2,2,2-trifluoropropyl, 1H,1H,2H,2H-nonafluorohexyl, 1H,1H,2H,2H-tridecafluorooctyl, 1H , 1H,6H-decafluorohexyl, 1H,1H,2H,2H,8H-dodecafluorooctyl, methoxymethyl, 2-trifluoromethoxyethyl, hydroxymethyl, 5-hydroxypentyl, 7-hydroxyheptyl, 3-aminopropyl , 4-carboxypentyl, 6-mercaptohexyl;
Cyclopentyl, cyclohexyl, 4-hydroxycyclohexyl;
Phenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl;
Benzyl, 4-fluorobenzyl, (4-trifluoromethylphenyl)methyl;
undec-10-en-1-yl;
etc.

R is preferably a C _1-8 alkyl group optionally substituted with an optionally protected amino group, more preferably a C _1-8 alkyl group, even more preferably a C _1-4 alkyl group. group, even more preferably a C _1-2 alkyl group, particularly preferably methyl.

The manufacturing method of the present invention will be explained below.
In the present invention, compound (4) is produced by a method including a step of reacting compound (1) with compound (2) in the presence of a base.

[Each symbol in the formula has the same meaning as above. ]
Compound (1) can be a commercially available product, or can be produced by a method known per se.
As the compound (1), a compound represented by the following formula (1a) is preferable.

[Each symbol in the formula has the same meaning as above. ]
Among these, compound (1a) in which X ¹ is a fluorine atom, a chlorine atom, or a bromine atom, and X ² and X ³ are each independently a fluorine atom or a chlorine atom is preferable, and X ¹ is a fluorine atom A compound (1a) in which X ² and X ³ are both fluorine atoms is more preferable.

Specific examples of compound (1a) include 1-chloro-1,2,3-trifluoro-1-propene, 1,3-dichloro-1,2-difluoro-1-propene, 3-bromo-1,1 , 2-trifluoro-1-propene, 3-chloro-1,1,2-trifluoro-1-propene, 1,1,2,3-tetrafluoro-1-propene are preferred, and 3-chloro-1, 1,2-trifluoro-1-propene and 1,1,2,3-tetrafluoro-1-propene are more preferred, and 1,1,2,3-tetrafluoro-1-propene is particularly preferred. Their structures are shown below.

In addition, compound (1) may be either a cis form or a trans form, or a mixture thereof. In the case of a mixture, the mixing ratio is arbitrary.

A commercially available product can be used as compound (2).
The compound (2) is preferably a C _1-8 alcohol which may be substituted with an optionally protected amino group, and methanol, ethanol, 1-propanol, 2-propanol, 3-aminopropanol and the like are preferable. Methanol and ethanol are more preferred, and methanol is particularly preferred.
The amount of compound (2) to be used is usually 0.001 to 10 mol, preferably 0.1 to 6.0 mol, per 1 mol of compound (1). Compound (2) may also serve as a reaction solvent, and in that case, the amount used is the amount of the solvent.

The base may be any base that can deprotonate compound (2) and convert it into an anionic nucleophile, such as alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, etc. ; Alkali metal C _1-4 alkoxides such as lithium methoxide, sodium methoxide, potassium methoxide, lithium ethoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide; Alkali metals such as lithium, sodium, potassium, etc. ; alkali metal hydrides such as sodium hydride and lithium hydride; and phosphazene bases (iminophosphorane bases) having the following structures.

The base is preferably an alkali metal hydroxide, an alkali metal C _1-4 alkoxide or an alkali metal hydride, more preferably an alkali metal hydroxide or an alkali metal C _1-4 alkoxide. be. Preferred specific examples include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal C _1-4 alkoxides such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide;
When the base is an alkali metal hydroxide, it is preferably used in the form of an aqueous solution.
When the base is an alkali metal C _1-4 alkoxide, it is preferably used in the form of an alcohol solution, and the alcohol is more preferably compound (2). That is, one preferred embodiment is one in which R in formula (2) is a C _1-4 alkyl group, the base is RONa or ROK, and the base is used in the form of an ROH solution. Preferred examples are sodium methoxide/methanol solution (R=methyl), sodium ethoxide/ethanol solution (R=ethyl) and potassium tert-butoxide/tert-butanol solution (R=tert-butyl).
The amount of the base used is usually 0.001 to 10 equivalents, preferably 0.01 to 3.0 equivalents, based on compound (1).

The reaction may be carried out in a solvent. Examples of solvents include ethers such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, methylcyclopentyl ether, tetrahydrofuran, and 1,4-dioxane; N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone. , amides such as 1,3-dimethyl-2-imidazolidinone; sulfoxides such as dimethyl sulfoxide; saturated hydrocarbons such as hexane, heptane, octane, and cyclohexane; ketones such as acetone and 2-butanone; sulfolane, Examples include water, and two or more of these may be used in combination. A preferred solvent is N,N-dimethylformamide.
When the base is an alkali metal C _1-4 alkoxide and is used in the form of an alcohol solution, the reaction may be carried out without the above-mentioned solvent.
The amount of solvent used is usually 0.1 to 100 times the volume of compound (1).

The reaction is preferably carried out by adding (preferably dropping) a base to a mixture of compound (1) and compound (2) (and a solvent if necessary). Specifically, the base is added (preferably added dropwise) to the compound (1) or a mixture of the compound (2) and a solution of the compound (1) in a solvent.
The reaction is usually carried out at a temperature in the range of 30 to 180°C, preferably in the range of 60 to 130°C.
Completion of the reaction can be confirmed by thin layer chromatography or the like.

If water is present in the reaction system, the reaction between compound (1) and compound (2) will proceed to the formation of compound (4) via compound (3); If not, compound (3) will remain.

[Each symbol in the formula has the same meaning as above. ]
Compound (3) reacts in the presence of water and is converted to compound (4).

[Each symbol in the formula has the same meaning as above. ]
Therefore, by carrying out the reaction between compound (1) and compound (2) in a reaction system containing water, it is possible to proceed to the formation of compound (4).

Specifically, the method of carrying out the reaction in a reaction system containing water includes: carrying out the reaction in a solvent containing water; carrying out the reaction using an aqueous alkali metal hydroxide solution as a base; carrying out the reaction using a compound (2) containing water. Examples of methods include carrying out the reaction; adding water during the reaction; and the like.
Regarding solvents containing water, N,N-dimethylformamide usually contains water in the range of 20 to 1300 ppm, and tetrahydrofuran usually contains water in the range of 10 to 1800 ppm.
Regarding compound (2) containing water, methanol usually contains water in a range of 100 to 5000 ppm, ethanol usually contains water in a range of 1 to 2000 ppm, and 2-propanol usually contains water in a range of 1 to 2000 ppm. contains water.
In addition, in this specification, "ppm" is a mass standard.
The amount of water in the reaction system is usually a catalytic amount per 1 mole of compound (1).
It is thought that a catalytic amount of water exhibits a catalytic effect on compound (2), thereby promoting the reaction in which compound (2) also reacts with compound (3) to produce compound (4). In addition, when water is present in a large amount rather than in a catalytic amount, it is considered that it also acts as a raw material that reacts with compound (3) to produce compound (4).

The temperature of the reaction between compound (1) and compound (2) in a reaction system containing water is usually in the range of 30 to 180°C, preferably in the range of 60 to 130°C.
Completion of the reaction can be confirmed by thin layer chromatography or the like.

Alternatively, compound (1) is reacted with compound (2) in a reaction system in the absence of water to obtain compound (3), which is then reacted in the presence of water to obtain compound (4). May be manufactured.

In this case, the solvent is usually a water-free solvent or a dehydrated solvent. Furthermore, as the base, alkali metal C _1-4 alkoxides are preferably used. Compound (2) is used after being dehydrated if necessary.

For example, when the base is an alkali metal C _1-4 alkoxide, the temperature of the reaction between compound (1) and compound (2) in a reaction system in the absence of water is usually in the range of 30 to 80°C, preferably The temperature ranges from 50 to 80°C.

The reaction of compound (3) in the presence of water may be carried out after isolating compound (3) from the reaction mixture of compound (1) and compound (2), but since it can be easily carried out, It is preferable to use the reaction mixture of (1) and compound (2) as is.
The temperature for the reaction of compound (3) in the presence of water is usually in the range of 80 to 180°C.
Completion of the reaction can be confirmed by thin layer chromatography or the like.

After completion of the reaction, the desired compound (4) can be isolated and/or purified from the reaction mixture by separation means such as concentration, crystallization, recrystallization, distillation, solvent extraction, fractional distillation, and chromatography according to conventional methods. .

Note that among compounds (3), compound (3a) is a new compound.

[In the formula, X ² and X ³ each independently represent a halogen atom, Y represents a halogen atom, and R ^a represents a C _1-8 alkyl group. ]
Among them, the compound (3a) in which X ² and X ³ are each independently a fluorine atom or a chlorine atom, Y is a fluorine atom, and R ^a is a C _1-2 alkyl group is preferred, More preferred is the compound (3a) in which X ² and X ³ are both fluorine atoms, Y is a fluorine atom, and R ^a is a C _1-2 alkyl group.
Specific preferred examples of compound (3a) include the following compounds.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited by these Examples.
[Analysis method]
The products obtained in Examples 1 to 3 were analyzed by GC and GC-MS. In both cases, RTX-200 was used as a column, and the temperature was -20°C for 5 min → 10°C/min → 250°C for 20 min.
Moisture content was measured by Karl Fischer titration method.

[Example 1]
1,1,2,3-tetrafluoro-1-propene (compound (1) in which X ¹ , X ² , X ³ and Y are all fluorine atoms) 0.77 g (1.3M, N,N-dimethylformamide 0.22 g of methanol (water content 400 ppm) was added to the solution (water content 300 ppm), 0.01 g of a 48% potassium hydroxide aqueous solution was added thereto, and the mixture was stirred at 120°C for 2 hours. According to GC analysis, a conversion rate of 35%, CH ₂ =CF-CF ₂ OCH ₃ was obtained in a yield of 5%, and CH ₂ =CF-COOCH ₃ was obtained in a yield of 30%. Furthermore, when GC-MS analysis was performed, two new peaks were confirmed. One was confirmed to have peaks and fragments that matched those of pure CH ₂ =CF-COOCH ₃ . The other fragment was the parent fragment 126, and other fragments such as 95, 81, and 31 were confirmed, and it was confirmed that the reaction occurred via the intermediate CH ₂ =CF-CF ₂ OCH ₃ . This solution was further reacted for 12 hours to obtain 100% conversion, 4% yield of CH ₂ ═CF-CF ₂ OCH ₃ and 96% yield of CH ₂ ═CF-COOCH ₃ .

[Example 2]
1,1,2,3-tetrafluoro-1-propene (compound (1) in which X ¹ , X ² , X ³ and Y are all fluorine atoms) 0.77 g (1.3M, N,N-dimethylformamide Solution: 0.22 g of methanol (water content 1200 ppm) was added to the solution (water content 800 ppm), 0.06 g of 28% sodium methoxide methanol solution was added thereto, and the mixture was stirred at 120°C for 8 hours. GC analysis showed that the conversion rate was 100%, CH ₂ =CF-CF ₂ OCH ₃ was obtained at 7%, and CH ₂ =CF-COOCH ₃ was obtained at 93%. Furthermore, when GC-MS analysis was carried out, as in Example 1, CH ₂ =CF-CF ₂ OCH ₃ and CH ₂ =CF-COOCH ₃ were confirmed.

[Example 3]
1,1,2,3-tetrafluoro-1-propene (compound (1) in which X ¹ , X ² , X ³ and Y are all fluorine atoms) 0.77 g (1.3M, N,N-dimethylformamide Solution: 1.64 g of 28% sodium methoxide methanol solution (water content 20 ppm) was added to the solution (water content 100 ppm), and the mixture was stirred at 50°C for 14 hours. According to GC analysis, a conversion rate of 91%, CH ₂ ═CF-CF ₂ OCH ₃ was obtained at 71%, and CH ₂ ═CF-COOCH ₃ was obtained at 19%. Furthermore, when GC-MS analysis was carried out, as in Example 1, CH ₂ =CF-CF ₂ OCH ₃ and CH ₂ =CF-COOCH ₃ were confirmed.

According to the present invention, halogenated acrylic esters can be produced in a safe and simple manner, and in a manner suitable for industrial production, without using highly toxic raw materials.

Claims (13)

A method for producing a compound represented by formula (4), comprising a step of reacting a compound represented by formula (1) with a compound represented by formula (2) in the presence of a base.

[In the formula,
X ¹ , X ² and X ³ each independently represent a halogen atom,
Y represents a halogen atom,
R represents a C _1-8 alkyl group, a C _3-8 cycloalkyl group, a C _7-14 aralkyl group or a C _6-10 aryl group,
Here, the C _1-8 alkyl group is a halogen atom, a cyano group, a C _1-4 alkoxy group, a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group. , optionally substituted with a group selected from an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group,
The C _3-8 cycloalkyl group, C _7-14 aralkyl group and C _6-10 aryl group are halogen atoms, cyano groups, C _1-4 alkyl groups, C _1-4 haloalkyl groups, and C _1-4 alkoxy groups. , a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group, an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group. Each may be substituted with a group. ] The manufacturing method according to claim 1, wherein the reaction is carried out in a reaction system containing water. The manufacturing method according to claim 1 or 2, wherein the reaction is performed in a solvent containing water. The manufacturing method according to claim 1 or 2, wherein water is added during the reaction. The manufacturing method according to any one of claims 1 to 4, wherein the base is an alkali metal C _1-4 alkoxide. The manufacturing method according to claim 5, wherein R in formula (2) is a C _1-4 alkyl group, and the base is RONa or ROK, which is used in the form of an ROH solution. The production method according to any one of claims 1 to 4, wherein the base is an alkali metal hydroxide and is used in the form of an aqueous solution. The manufacturing method according to any one of claims 1 to 7, wherein the reaction is carried out within a range of 30 to 180°C. The manufacturing method according to any one of claims 1 to 8, wherein Y is a fluorine atom. The manufacturing method according to any one of claims 1 to 9, wherein R is a C _1-2 alkyl group. The manufacturing method according to any one of claims 1 to 10, wherein X ² and X ³ are both fluorine atoms. The manufacturing method according to any one of claims 1 to 11, wherein X ¹ is a fluorine atom. A compound represented by formula (1) is reacted with a compound represented by formula (2) in the presence of a base, and then the resulting reaction mixture is reacted in the presence of water. 4) A method for producing the compound represented by.

[In the formula,
X ¹ , X ² and X ³ each independently represent a halogen atom,
Y represents a halogen atom,
R represents a C _1-8 alkyl group, a C _3-8 cycloalkyl group, a C _7-14 aralkyl group or a C _6-10 aryl group,
Here, the C _1-8 alkyl group is a halogen atom, a cyano group, a C _1-4 alkoxy group, a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group. , optionally substituted with a group selected from an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group,
The C _3-8 cycloalkyl group, C _7-14 aralkyl group and C _6-10 aryl group are halogen atoms, cyano groups, C _1-4 alkyl groups, C _1-4 haloalkyl groups, and C _1-4 alkoxy groups. , a C _1-4 haloalkoxy group, an optionally protected amino group, an optionally protected carboxyl group, an optionally protected hydroxy group, an optionally protected sulfanyl group, and a vinyl group. Each may be substituted with a group. ]