Method for producing 2-fluoromethylacrylic acid ester derivatives

Abstract

To provide an inexpensive, safe and industrial production method that substitutes a hydroxy group of a 2-hydroxymethylacrylate derivative with a fluorine atom.SOLUTION: A method for producing a compound represented by general formula (3) includes reacting a compound represented by general formula (1) with 1,1,2,2-tetrafluoro-N,N-dimethylethylamine in an organic solvent, where R1 is a cyclohexyl group, a naphthyl-1-yl group or the like, R2 is a methyl group or the like.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a 2-fluoromethylacrylic ester derivative. The 2-fluoromethylacrylic acid ester derivative obtained by the production method of the present invention can substitute one optically active fluorine atom for various substrates by dynamic asymmetric control in the presence of a metal catalyst such as palladium and a chiral ligand, and the obtained optically active compound is a useful compound as a production intermediate for pharmaceuticals, agrochemicals, or electronic materials. [Background technology]

[0002] Conventionally, as a method for producing the 2-fluoromethylacrylic acid ester derivative of the present invention, a method in which the 2-hydroxymethylacrylic acid ester derivative of the present invention is fluorinated with N,N-diethylaminosulfur trifluoride (hereinafter abbreviated as DAST) has been known (for example, Non-Patent Document 1). The method described in Non-Patent Document 1 has the problem that it requires the use of DAST, which is expensive and has stability problems, and therefore may not be possible to implement on an industrial scale. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Nirio Shibata et al., Angew. Chim. Int. Ed. 2014, 53, 517-520. Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a method for substituting the hydroxyl group of the 2-hydroxymethylacrylic ester derivative of the present invention with a fluorine atom, which is inexpensive, safe and industrially feasible. [Means for solving the problem]

[0005] The present inventors conducted extensive research into a method for producing a 2-fluoromethylacrylic acid derivative from a 2-hydroxymethylacrylic acid derivative, and as a result discovered that a 2-fluoromethylacrylic acid ester derivative can be produced by using inexpensive and safe 1,1,2,2-tetrafluoro-N,N-dimethylethylamine (hereinafter abbreviated as TFEDMA), thereby completing the present invention.

[0006] That is, the present invention relates to a compound represented by the following general formula (1): [ka] [In formula (1), R 1 represents a cyclohexyl group, a naphthyl-1-yl group, a naphthyl-2-yl group, a 2-phenylethyl group, or the following general formula (2)] [ka] (In formula (2), R 3 teeth, Hydrogen atom, methyl group, halogen atom, nitro group, cyano group, trifluoromethyl group, or methoxycarbonyl group), and R 2 represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group. The present invention relates to a method for producing a 2-hydroxymethylacrylic acid ester derivative represented by the following general formula (3): [ka] [In formula (3), R 1 represents a cyclohexyl group, a naphthyl-1-yl group, a naphthyl-2-yl group, a 2-phenylethyl group, or the following general formula (2)] [ka] (In formula (2), R 3 teeth, Hydrogen atom,methyl group, halogen atom, nitro group, cyano group, trifluoromethyl group, or methoxycarbonyl group), and R 2 represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group. The present invention provides a method for producing a 2-fluoromethylacrylic ester derivative represented by the following formula: Effect of the Invention

[0007] INDUSTRIAL APPLICABILITY The present invention makes it possible to economically and industrially produce 2-fluoromethylacrylic acid derivatives, which are useful as raw materials for the synthesis of various pharmaceuticals. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The present invention will be described in detail below. A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of compounds in which is a methyl group include methyl 2-[hydroxy(phenyl)methyl]acrylate, methyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, methyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, methyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, methyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, methyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, methyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, methyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, methyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, methyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, methyl 2-[hydroxy(2-bromophenyl)methyl]acrylate, methyl 2-[hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[hydroxy(4-bromophenyl)methyl]acrylate, and methyl 2-[hydroxy(2-iodophenyl)methyl]acrylate, methyl 2-[hydroxy(3-iodophenyl)methyl]acrylate, methyl 2-[hydroxy(4-iodophenyl)methyl]acrylate, methyl 2-[hydroxy(2-nitrophenyl)methyl]acrylate, methyl 2-[hydroxy(3-nitrophenyl)methyl]acrylate, methyl 2-[hydroxy(4-nitrophenyl)methyl]acrylate, methyl 2-[hydroxy(2-cyanophenyl)methyl]acrylate, methyl 2-[hydroxy(3-cyanophenyl)methyl]acrylate, methyl 2-[hydroxy(4-cyanophenyl)methyl]acrylate, methyl 2-{hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, methyl 2-{hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, methyl 2-{hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, methyl 2-[Hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, methyl 2-[Hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, methylExamples of such acrylates include 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, methyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, methyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, methyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and methyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0009] A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of those in which is an ethyl group include ethyl 2-[hydroxy(phenyl)methyl]acrylate, ethyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, ethyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, ethyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, ethyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, ethyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, ethyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, ethyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, ethyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, ethyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, ethyl 2-[hydroxy(2-bromophenyl)methyl]acrylate, ethyl 2-[hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[hydroxy(4-bromophenyl)methyl]acrylate, ethyl 2-[Hydroxy(2-iodophenyl)methyl]acrylate, ethyl 2-[Hydroxy(3-iodophenyl)methyl]acrylate, ethyl 2-[Hydroxy(4-iodophenyl)methyl]acrylate, ethyl 2-[Hydroxy(2-nitrophenyl)methyl]acrylate, ethyl 2-[Hydroxy(3-nitrophenyl)methyl]acrylate, ethyl 2-[Hydroxy(4-nitrophenyl)methyl]acrylate, ethyl 2-[Hydroxy(2-cyanophenyl)methyl]acrylate, ethyl 2-[Hydroxy(3-cyanophenyl)methyl]acrylate, ethyl 2-[Hydroxy(4-cyanophenyl)methyl]acrylate, ethyl 2-{Hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, ethyl 2-{Hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, ethyl 2-{Hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, ethyl 2-[Hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, ethyl 2-[Hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, ethylExamples of the acrylates include 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, ethyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, ethyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, ethyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and ethyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0010] A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of those in which is an n-propyl group include n-propyl 2-[hydroxy(phenyl)methyl]acrylate, n-propyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, n-propyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, n-propyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, n-propyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, n-propyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, n-propyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, n-propyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, n-propyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, n-propyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, n-propyl 2-[hydroxy(2-bromophenyl)methyl]acrylate, and n-propyl 2-[Hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[Hydroxy(4-bromophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(2-iodophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(3-iodophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(4-iodophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(2-nitrophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(3-nitrophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(4-nitrophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(2-cyanophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(3-cyanophenyl)methyl]acrylate, n-propyl 2-[Hydroxy(4-cyanophenyl)methyl]acrylate, n-propyl 2-{hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, n-propyl 2-{hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, n-propyl 2-{hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, n-propylExamples of the acrylates include 2-[hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, n-propyl 2-[hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, n-propyl 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, n-propyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, n-propyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, n-propyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and n-propyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0011] A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of those in which is an isopropyl group include isopropyl 2-[hydroxy(phenyl)methyl]acrylate, isopropyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, isopropyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, isopropyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, isopropyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, isopropyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, isopropyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, isopropyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, isopropyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, isopropyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, isopropyl 2-[hydroxy(2-bromophenyl)methyl]acrylate, and isopropyl 2-[hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[hydroxy(4-bromophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(2-iodophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(3-iodophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(4-iodophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(2-nitrophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(3-nitrophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(4-nitrophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(2-cyanophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(3-cyanophenyl)methyl]acrylate, iso-propyl 2-[hydroxy(4-cyanophenyl)methyl]acrylate, iso-propyl 2-{hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, iso-propyl 2-{hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, iso-propylExamples of the acrylates include 2-{hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, isopropyl 2-[hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, isopropyl 2-[hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, isopropyl 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, isopropyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, isopropyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, isopropyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and isopropyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0012] A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of those in which is an n-butyl group include n-butyl 2-[hydroxy(phenyl)methyl]acrylate, n-butyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, n-butyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, n-butyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, n-butyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, n-butyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, n-butyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, n-butyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, n-butyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, n-butyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, n-butyl 2-[hydroxy(2-bromophenyl)methyl]acrylate, and n-butyl 2-[Hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[Hydroxy(4-bromophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(2-iodophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(3-iodophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(4-iodophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(2-nitrophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(3-nitrophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(4-nitrophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(2-cyanophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(3-cyanophenyl)methyl]acrylate, n-butyl 2-[Hydroxy(4-cyanophenyl)methyl]acrylate, n-butyl 2-{hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, n-butyl 2-{hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, n-butyl 2-{hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, n-butyl 2-[hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, n-butylExamples of the acrylates include 2-[hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, n-butyl 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, n-butyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, n-butyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, n-butyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and n-butyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0013] A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of the acrylate having an iso-butyl group include iso-butyl 2-[hydroxy(phenyl)methyl]acrylate, iso-butyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, iso-butyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, iso-butyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, iso-butyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, iso-butyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, iso-butyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, iso-butyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, iso-butyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, iso-butyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, iso-butyl 2-[hydroxy(2-bromophenyl)methyl]acrylate, and iso-butyl 2-[Hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[Hydroxy(4-bromophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(2-iodophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(3-iodophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(4-iodophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(2-nitrophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(3-nitrophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(4-nitrophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(2-cyanophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(3-cyanophenyl)methyl]acrylate, iso-butyl 2-[Hydroxy(4-cyanophenyl)methyl]acrylate, iso-butyl 2-{hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, iso-butyl 2-{hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, iso-butylExamples of the acrylates include 2-{hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, iso-butyl 2-[hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, iso-butyl 2-[hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, iso-butyl 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, iso-butyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, iso-butyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, iso-butyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and iso-butyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0014] A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of those in which is a sec-butyl group include sec-butyl 2-[hydroxy(phenyl)methyl]acrylate, sec-butyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, sec-butyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, sec-butyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, sec-butyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, sec-butyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, sec-butyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, sec-butyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, sec-butyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, sec-butyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, sec-butyl 2-[hydroxy(2-bromophenyl)methyl]acrylate, and sec-butyl 2-[Hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[Hydroxy(4-bromophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(2-iodophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(3-iodophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(4-iodophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(2-nitrophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(3-nitrophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(4-nitrophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(2-cyanophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(3-cyanophenyl)methyl]acrylate, sec-butyl 2-[Hydroxy(4-cyanophenyl)methyl]acrylate, sec-butyl 2-{hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, sec-butyl 2-{hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, sec-butylExamples of the hydroxyalkyl groups include 2-{hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, sec-butyl 2-[hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, sec-butyl 2-[hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, sec-butyl 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, sec-butyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, sec-butyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, sec-butyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and sec-butyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0015] A 2-hydroxymethyl acrylic acid ester derivative represented by the general formula (1) applicable to the present invention, R 2Specific examples of those in which is a tert-butyl group include tert-butyl 2-[hydroxy(phenyl)methyl]acrylate, tert-butyl 2-[hydroxy(2-methylphenyl)methyl]acrylate, tert-butyl 2-[hydroxy(3-methylphenyl)methyl]acrylate, tert-butyl 2-[hydroxy(4-methylphenyl)methyl]acrylate, tert-butyl 2-[hydroxy(2-fluorophenyl)methyl]acrylate, tert-butyl 2-[hydroxy(3-fluorophenyl)methyl]acrylate, tert-butyl 2-[hydroxy(4-fluorophenyl)methyl]acrylate, tert-butyl 2-[hydroxy(2-chlorophenyl)methyl]acrylate, tert-butyl 2-[hydroxy(3-chlorophenyl)methyl]acrylate, tert-butyl 2-[hydroxy(4-chlorophenyl)methyl]acrylate, and tert-butyl 2-[Hydroxy(2-bromophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(3-bromophenyl)methyl]acrylate, methyl 2-[Hydroxy(4-bromophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(2-iodophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(3-iodophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(4-iodophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(2-nitrophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(3-nitrophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(4-nitrophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(2-cyanophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(3-cyanophenyl)methyl]acrylate, tert-butyl 2-[Hydroxy(4-cyanophenyl)methyl]acrylate, tert-butyl 2-{hydroxy[2-(trifluoromethyl)phenyl]methyl}acrylate, tert-butyl 2-{hydroxy[3-(trifluoromethyl)phenyl]methyl}acrylate, tert-butylExamples of the acrylates include 2-{hydroxy[4-(trifluoromethyl)phenyl]methyl}acrylate, tert-butyl 2-[hydroxy(2-methoxycarbonylphenyl)methyl]acrylate, tert-butyl 2-[hydroxy(3-methoxycarbonylphenyl)methyl]acrylate, tert-butyl 2-[hydroxy(4-methoxycarbonylphenyl)methyl]acrylate, tert-butyl 2-[hydroxy(naphthyl-1-yl)methyl]acrylate, tert-butyl 2-[hydroxy(naphthyl-2-yl)methyl]acrylate, tert-butyl 2-[hydroxy(cyclohexyl)methyl]acrylate, and tert-butyl 3-hydroxy-2-methylene-5-phenylpentanoate.

[0016] The 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) can be produced by the present invention, where R 2Specific examples of the methyl group include methyl 2-[fluoro(phenyl)methyl]acrylate, methyl 2-[fluoro(2-methylphenyl)methyl]acrylate, methyl 2-[fluoro(3-methylphenyl)methyl]acrylate, methyl 2-[fluoro(4-methylphenyl)methyl]acrylate, methyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, methyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, methyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, methyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, methyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, methyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, methyl 2-[fluoro(2-bromophenyl)methyl]acrylate, methyl 2-[fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[fluoro(4-bromophenyl)methyl]acrylate, methyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, methyl 2-[fluoro(3-iodophenyl)methyl]acrylate, methyl 2-[fluoro(4-iodophenyl)methyl]acrylate, methyl 2-[fluoro(2-nitrophenyl)methyl]acrylate, methyl 2-[fluoro(3-nitrophenyl)methyl]acrylate, methyl 2-[fluoro(4-nitrophenyl)methyl]acrylate, methyl 2-[fluoro(2-cyanophenyl)methyl]acrylate, methyl 2-[fluoro(3-cyanophenyl)methyl]acrylate, methyl 2-[fluoro(4-cyanophenyl)methyl]acrylate, methyl 2-{fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, methyl 2-{fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, methyl 2-{fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, methyl 2-[Fluoro(2-methoxycarbonylphenyl)methyl]acrylate, methyl 2-[Fluoro(3-methoxycarbonylphenyl)methyl]acrylate, methyl 2-[Fluoro(4-methoxycarbonylphenyl)methyl]acrylate, methylExamples of such fluoroalkyl groups include 2-[fluoro(naphthyl-1-yl)methyl]acrylate, methyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, methyl 2-[fluoro(cyclohexyl)methyl]acrylate, and methyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0017] A 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) applicable to the present invention, R 2Specific examples of the ethyl group include ethyl 2-[fluoro(phenyl)methyl]acrylate, ethyl 2-[fluoro(2-methylphenyl)methyl]acrylate, ethyl 2-[fluoro(3-methylphenyl)methyl]acrylate, ethyl 2-[fluoro(4-methylphenyl)methyl]acrylate, ethyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, ethyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, ethyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, ethyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, ethyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, ethyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, ethyl 2-[fluoro(2-bromophenyl)methyl]acrylate, ethyl 2-[fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[fluoro(4-bromophenyl)methyl]acrylate, ethyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, ethyl 2-[Fluoro(3-iodophenyl)methyl]acrylate, ethyl 2-[Fluoro(4-iodophenyl)methyl]acrylate, ethyl 2-[Fluoro(2-nitrophenyl)methyl]acrylate, ethyl 2-[Fluoro(3-nitrophenyl)methyl]acrylate, ethyl 2-[Fluoro(4-nitrophenyl)methyl]acrylate, ethyl 2-[Fluoro(2-cyanophenyl)methyl]acrylate, ethyl 2-[Fluoro(3-cyanophenyl)methyl]acrylate, ethyl 2-[Fluoro(4-cyanophenyl)methyl]acrylate, ethyl 2-{Fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, ethyl 2-{Fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, ethyl 2-{Fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, ethyl 2-[Fluoro(2-methoxycarbonylphenyl)methyl]acrylate, ethyl 2-[Fluoro(3-methoxycarbonylphenyl)methyl]acrylate, ethyl 2-[Fluoro(4-methoxycarbonylphenyl)methyl]acrylate, ethylExamples of the fluoroalkyl groups include 2-[fluoro(naphthyl-1-yl)methyl]acrylate, ethyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, ethyl 2-[fluoro(cyclohexyl)methyl]acrylate, and ethyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0018] A 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) applicable to the present invention, R 2Specific examples of those in which is an n-propyl group include n-propyl 2-[fluoro(phenyl)methyl]acrylate, n-propyl 2-[fluoro(2-methylphenyl)methyl]acrylate, n-propyl 2-[fluoro(3-methylphenyl)methyl]acrylate, n-propyl 2-[fluoro(4-methylphenyl)methyl]acrylate, n-propyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, n-propyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, n-propyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, n-propyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, n-propyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, n-propyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, n-propyl 2-[fluoro(2-bromophenyl)methyl]acrylate, and n-propyl 2-[Fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[Fluoro(4-bromophenyl)methyl]acrylate, n-propyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, n-propyl 2-[Fluoro(3-iodophenyl)methyl]acrylate, n-propyl 2-[Fluoro(4-iodophenyl)methyl]acrylate, n-propyl 2-[Fluoro(2-nitrophenyl)methyl]acrylate, n-propyl 2-[Fluoro(3-nitrophenyl)methyl]acrylate, n-propyl 2-[Fluoro(4-nitrophenyl)methyl]acrylate, n-propyl 2-[Fluoro(2-cyanophenyl)methyl]acrylate, n-propyl 2-[Fluoro(3-cyanophenyl)methyl]acrylate, n-propyl 2-[Fluoro(4-cyanophenyl)methyl]acrylate, n-propyl 2-{fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, n-propyl 2-{fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, n-propyl 2-{fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, n-propyl 2-[fluoro(2-methoxycarbonylphenyl)methyl]acrylate, n-propylExamples of such acrylates include 2-[fluoro(3-methoxycarbonylphenyl)methyl]acrylate, n-propyl 2-[fluoro(4-methoxycarbonylphenyl)methyl]acrylate, n-propyl 2-[fluoro(naphthyl-1-yl)methyl]acrylate, n-propyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, n-propyl 2-[fluoro(cyclohexyl)methyl]acrylate, and n-propyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0019] A 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) applicable to the present invention, R 2Specific examples of the compound having an isopropyl group include isopropyl 2-[fluoro(phenyl)methyl]acrylate, isopropyl 2-[fluoro(2-methylphenyl)methyl]acrylate, isopropyl 2-[fluoro(3-methylphenyl)methyl]acrylate, isopropyl 2-[fluoro(4-methylphenyl)methyl]acrylate, isopropyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, isopropyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, isopropyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, isopropyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, isopropyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, isopropyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, isopropyl 2-[fluoro(2-bromophenyl)methyl]acrylate, and isopropyl 2-[Fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[Fluoro(4-bromophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(3-iodophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(4-iodophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(2-nitrophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(3-nitrophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(4-nitrophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(2-cyanophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(3-cyanophenyl)methyl]acrylate, iso-propyl 2-[Fluoro(4-cyanophenyl)methyl]acrylate, iso-propyl 2-{fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, iso-propyl 2-{fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, iso-propylExamples of the fluoroalkyl groups include 2-{fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, iso-propyl 2-[fluoro(2-methoxycarbonylphenyl)methyl]acrylate, iso-propyl 2-[fluoro(3-methoxycarbonylphenyl)methyl]acrylate, iso-propyl 2-[fluoro(4-methoxycarbonylphenyl)methyl]acrylate, iso-propyl 2-[fluoro(naphthyl-1-yl)methyl]acrylate, iso-propyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, iso-propyl 2-[fluoro(cyclohexyl)methyl]acrylate, and iso-propyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0020] A 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) applicable to the present invention, R 2Specific examples of those in which is an n-butyl group include n-butyl 2-[fluoro(phenyl)methyl]acrylate, n-butyl 2-[fluoro(2-methylphenyl)methyl]acrylate, n-butyl 2-[fluoro(3-methylphenyl)methyl]acrylate, n-butyl 2-[fluoro(4-methylphenyl)methyl]acrylate, n-butyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, n-butyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, n-butyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, n-butyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, n-butyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, n-butyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, n-butyl 2-[fluoro(2-bromophenyl)methyl]acrylate, and n-butyl 2-[Fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[Fluoro(4-bromophenyl)methyl]acrylate, n-butyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, n-butyl 2-[Fluoro(3-iodophenyl)methyl]acrylate, n-butyl 2-[Fluoro(4-iodophenyl)methyl]acrylate, n-butyl 2-[Fluoro(2-nitrophenyl)methyl]acrylate, n-butyl 2-[Fluoro(3-nitrophenyl)methyl]acrylate, n-butyl 2-[Fluoro(4-nitrophenyl)methyl]acrylate, n-butyl 2-[Fluoro(2-cyanophenyl)methyl]acrylate, n-butyl 2-[Fluoro(3-cyanophenyl)methyl]acrylate, n-butyl 2-[Fluoro(4-cyanophenyl)methyl]acrylate, n-butyl 2-{Fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, n-butyl 2-{Fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, n-butyl 2-{Fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, n-butyl 2-[Fluoro(2-methoxycarbonylphenyl)methyl]acrylate, n-butylExamples of the fluoro(3-methoxycarbonylphenyl)methyl acrylate include 2-[fluoro(3-methoxycarbonylphenyl)methyl]acrylate, n-butyl 2-[fluoro(4-methoxycarbonylphenyl)methyl]acrylate, n-butyl 2-[fluoro(naphthyl-1-yl)methyl]acrylate, n-butyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, n-butyl 2-[fluoro(cyclohexyl)methyl]acrylate, and n-butyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0021] A 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) applicable to the present invention, R 2Specific examples of the acrylate having an iso-butyl group include iso-butyl 2-[fluoro(phenyl)methyl]acrylate, iso-butyl 2-[fluoro(2-methylphenyl)methyl]acrylate, iso-butyl 2-[fluoro(3-methylphenyl)methyl]acrylate, iso-butyl 2-[fluoro(4-methylphenyl)methyl]acrylate, iso-butyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, iso-butyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, iso-butyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, iso-butyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, iso-butyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, iso-butyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, iso-butyl 2-[fluoro(2-bromophenyl)methyl]acrylate, and iso-butyl 2-[Fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[Fluoro(4-bromophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(3-iodophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(4-iodophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(2-nitrophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(3-nitrophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(4-nitrophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(2-cyanophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(3-cyanophenyl)methyl]acrylate, iso-butyl 2-[Fluoro(4-cyanophenyl)methyl]acrylate, iso-butyl 2-{fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, iso-butyl 2-{fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, iso-butyl 2-{fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, iso-butylExamples of the fluoro(2-methoxycarbonylphenyl)methyl acrylate include 2-[fluoro(2-methoxycarbonylphenyl)methyl]acrylate, iso-butyl 2-[fluoro(3-methoxycarbonylphenyl)methyl]acrylate, iso-butyl 2-[fluoro(4-methoxycarbonylphenyl)methyl]acrylate, iso-butyl 2-[fluoro(naphthyl-1-yl)methyl]acrylate, iso-butyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, iso-butyl 2-[fluoro(cyclohexyl)methyl]acrylate, and iso-butyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0022] A 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) applicable to the present invention, R 2Specific examples of those in which is a sec-butyl group include sec-butyl 2-[fluoro(phenyl)methyl]acrylate, sec-butyl 2-[fluoro(2-methylphenyl)methyl]acrylate, sec-butyl 2-[fluoro(3-methylphenyl)methyl]acrylate, sec-butyl 2-[fluoro(4-methylphenyl)methyl]acrylate, sec-butyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, sec-butyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, sec-butyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, sec-butyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, sec-butyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, sec-butyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, sec-butyl 2-[fluoro(2-bromophenyl)methyl]acrylate, and sec-butyl 2-[Fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[Fluoro(4-bromophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(3-iodophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(4-iodophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(2-nitrophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(3-nitrophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(4-nitrophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(2-cyanophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(3-cyanophenyl)methyl]acrylate, sec-butyl 2-[Fluoro(4-cyanophenyl)methyl]acrylate, sec-butyl 2-{fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, sec-butyl 2-{fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, sec-butyl 2-{fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, sec-butylExamples of the fluoro(2-methoxycarbonylphenyl)methyl acrylate include 2-[fluoro(2-methoxycarbonylphenyl)methyl]acrylate, sec-butyl 2-[fluoro(3-methoxycarbonylphenyl)methyl]acrylate, sec-butyl 2-[fluoro(4-methoxycarbonylphenyl)methyl]acrylate, sec-butyl 2-[fluoro(naphthyl-1-yl)methyl]acrylate, sec-butyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, sec-butyl 2-[fluoro(cyclohexyl)methyl]acrylate, and sec-butyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0023] A 2-fluoromethylacrylic acid ester derivative represented by the general formula (3) applicable to the present invention, R 2Specific examples of those in which is a tert-butyl group include tert-butyl 2-[fluoro(phenyl)methyl]acrylate, tert-butyl 2-[fluoro(2-methylphenyl)methyl]acrylate, tert-butyl 2-[fluoro(3-methylphenyl)methyl]acrylate, tert-butyl 2-[fluoro(4-methylphenyl)methyl]acrylate, tert-butyl 2-[fluoro(2-fluorophenyl)methyl]acrylate, tert-butyl 2-[fluoro(3-fluorophenyl)methyl]acrylate, tert-butyl 2-[fluoro(4-fluorophenyl)methyl]acrylate, tert-butyl 2-[fluoro(2-chlorophenyl)methyl]acrylate, tert-butyl 2-[fluoro(3-chlorophenyl)methyl]acrylate, tert-butyl 2-[fluoro(4-chlorophenyl)methyl]acrylate, and tert-butyl 2-[Fluoro(2-bromophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(3-bromophenyl)methyl]acrylate, methyl 2-[Fluoro(4-bromophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(2-iodophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(3-iodophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(4-iodophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(2-nitrophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(3-nitrophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(4-nitrophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(2-cyanophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(3-cyanophenyl)methyl]acrylate, tert-butyl 2-[Fluoro(4-cyanophenyl)methyl]acrylate, tert-butyl 2-{fluoro[2-(trifluoromethyl)phenyl]methyl}acrylate, tert-butyl 2-{fluoro[3-(trifluoromethyl)phenyl]methyl}acrylate, tert-butylExamples of the fluoroalkyl groups include 2-{fluoro[4-(trifluoromethyl)phenyl]methyl}acrylate, tert-butyl 2-[fluoro(2-methoxycarbonylphenyl)methyl]acrylate, tert-butyl 2-[fluoro(3-methoxycarbonylphenyl)methyl]acrylate, tert-butyl 2-[fluoro(4-methoxycarbonylphenyl)methyl]acrylate, tert-butyl 2-[fluoro(naphthyl-1-yl)methyl]acrylate, tert-butyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate, tert-butyl 2-[fluoro(cyclohexyl)methyl]acrylate, and tert-butyl 3-fluoro-2-methylene-5-phenylpentanoate.

[0024] The amount of 1,1,2,2-tetrafluoro-N,N-dimethylethylamine used in the present invention is preferably within the range of 1.0 to 3.0 moles per mole of the 2-hydroxymethylacrylic acid ester derivative represented by the general formula (1) used in the reaction.

[0025] The organic solvent applicable to the present invention is not particularly limited as long as it is inert to the reaction. Examples of the hydrocarbons include aliphatic hydrocarbons such as pentane, hexane, and octane; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, and xylene; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methylcyclopentyl ether, and anisole; and halogenated aliphatic hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform. Among these, halogenated aliphatic hydrocarbons are preferred from the viewpoint of the solubility of the raw material 2-hydroxymethylacrylic acid ester derivative represented by general formula (1) and the product 2-fluoromethylacrylic acid ester derivative represented by general formula (2), and it is advisable to use them in an amount 10 to 200 times by weight relative to the weight of the 2-hydroxymethylacrylic acid ester derivative represented by general formula (1) used in the reaction.

[0026] The reaction temperature and time of the present invention are −40° C. to 40° C., and the reaction is completed by carrying out the reaction for 10 minutes to 6 hours.

[0027] The post-treatment after the reaction of the present invention can be carried out by a known method. For example, the reaction mixture may be neutralized with a saturated aqueous solution of sodium hydrogen carbonate, extracted with an organic solvent such as dichloromethane, dried with a drying agent such as sodium sulfate, filtered, and concentrated to obtain the target product as a crude product, which may then be purified by silica gel column chromatography or the like to obtain a purified target product. EXAMPLES

[0028] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0029] The following instruments were used for the analysis: 1 H-NMR(300 MHz), 19 F-NMR (282 MHz): Varian Mercury 300. EI-MS: JMS-Q1050GC Master-Quad GC / MS manufactured by JEOL.

[0030] The raw material, methyl 2-[hydroxy(substituted)methyl]acrylate, was prepared according to the route shown in the following formula (A) described in the following literature. [ka] Literature: Yves Fort, et. al., Tetrahedron(1992), 48(31), 6371-84

[0031] Example 1 Preparation of methyl 2-[fluoro(phenyl)methyl]acrylate (3a) [ka]

[0032] Methyl 2-[hydroxy(phenyl)methyl]acrylate (1a) (38.4 mg, 0.2 mmol) and dichloromethane (2.0 mL) were charged into a Teflon (registered trademark) reactor equipped with a stirrer, and after cooling to 0°C, TFEDMA (36.5 μL, 0.3 mmol, 1.5 equiv.) was added thereto and reacted at room temperature for 20 minutes. After completion of the reaction, the mixture was cooled to 0°C, and then a saturated aqueous solution of sodium bicarbonate was added, and the liquids were separated. The aqueous layer was extracted with dichloromethane, and the resulting organic layers were combined, dried over sodium sulfate, filtered, and concentrated to obtain a crude product. The obtained crude product was purified by silica gel column chromatography (hexane / diethyl ether=20 / 1 vol / vol) to obtain the target compound, methyl 2-[hydroxy(phenyl)methyl]acrylate (3a) (21.8 mg, 0.118 mmol, yield=59%) as a colorless transparent liquid.

[0033] The results of the analysis of the target substance are shown below. 1 H-NMR (300MHz, CDCl3)δ:7.44-7.32(m,5H),6.47-6.45(m,1H),6.29(d,J=45.9Hz,1H),6.03(brs,1H),3.72(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-171.27(d,J=46.6Hz,1F)ppm. MS(EI)m / z:[M] + 193.

[0034] Examples 2 to 19 Preparation of various acrylic acid ester derivatives The same reaction apparatus as in Example 1 was used, and the same reaction as in Example 1 was carried out, except that the raw material methyl 2-[hydroxy(phenyl)methyl]acrylate (1a) (38.4 mg, 0.2 mmol) was replaced with the 2-[hydroxy(substituted)methyl]acrylate derivative shown in Table 1. After the reaction was completed, the various crude products obtained were purified as described in the margin to obtain the target 2-[fluoro(substituted)methyl]acrylate derivative (3). The results are shown in Table 1.

[0035] [Table 1] TIFF0007652598000008.tif194141

[0036] 1) Methyl 2-[fluoro(4-methylphenyl)methyl]acrylate (3b) The obtained crude product was purified with hexane / ethyl acetate=20 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR(300MHz,CDCl3)δ:7.28(d,J=9.1Hz,2H),7.18(d,J=7.6Hz,2H),6.45-6.44( m,1H),6.25(d,J=46.2Hz,1H),6.03(d,J=1.0Hz,1H),3.71(s,3H),2.36(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-169.75(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 208. 2) Methyl 2-[fluoro(3-methylphenyl)methyl]acrylate (3c) The obtained crude product was purified with hexane / ethyl acetate=45 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:7.28-7.17(m,4H),6.45(s,1H),6.25(d,J=45.9Hz,1H),6.02(s,1H),3.72(s,3H),2.36(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-170.66(d,J=46.6Hz,1F)ppm. MS(EI)m / z:[M] + 208. 3) Methyl 2-[fluoro(2-methylphenyl)methyl]acrylate (3d) The obtained crude product was purified with hexane / ethyl acetate=35 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR(300MHz,CDCl3)δ:7.33(d,J=7.9Hz,1H),7.29-7.18(m,3H),6.55(d,J= 45.9Hz,2H),6.49(s,1H),5.88(d,J=0.9Hz,1H),3.75(s,3H),2.40(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-173.22(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 208. 4) Methyl 2-[fluoro(4-chlorophenyl)methyl]acrylate (3e) The obtained crude product was purified with hexane / ethyl acetate=20 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:7.37-7.31(m,4H),6.46(d-like,J=2.1Hz,1H),6.24(d,J=45.9Hz,1H),6.04(s,1H),3.72(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-171.96(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 228. 5) Methyl 2-[fluoro(4-bromophenyl)methyl]acrylate (3f) The obtained crude product was purified with hexane / ethyl acetate=20 / 1 (vol / vol). Colorless transparent liquid. 1H-NMR (300MHz, CDCl3)δ:7.51(d,J=7.9Hz,2H),7.27(dd,J=7.6,1.8Hz,2H),6.46(d,J=2.9Hz,1H),6.23(d,J=45.9Hz,1H),6.04(s,1H),3.72(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-172.39(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 272. 6) Methyl 2-[fluoro(3-bromophenyl)methyl]acrylate (3g) The obtained crude product was purified with hexane / ethyl acetate=35 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR(300MHz,CDCl3)δ:7.53(s,1H),7.48(d,J=7.9Hz,1H),7.34-7.32(m,1H),7.27-7 .22(m,1H),6.48(d,J=2.9Hz,1H),6.23(d,J=45.9Hz,1H),6.05(s,1H),3.73(s,4H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-172.73(d,J=46.6Hz,1F)ppm. MS(EI)m / z:[M] + 272. 7) Methyl 2-[fluoro(2-bromophenyl)methyl]acrylate (3h) The obtained crude product was purified with hexane / ethyl acetate=30 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR(300MHz,CDCl3)δ:7.59(d-like,J=7.9Hz,1H),7.46(dd,J=7.8,1.6Hz,1H),7.37(t,J=7.5 Hz,1H),7.23(t,J=7.8Hz,1H),6.67(d,J=45.0Hz,1H),6.52(s,1H),5.78(s,1H),3.78(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-173.57(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M-Br] + 193. 8) Methyl 2-[fluoro(4-nitrophenyl)methyl]acrylate (3i) The obtained crude product was purified with hexane / ethyl acetate=20 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:8.23(d,J=8.2Hz,2H),7.58(d,J=8.2Hz,2H),6.51(d,J=2.6Hz,1H),6.36(d,J=45.6Hz,1H),6.09(s,1H),3.74(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-176.11(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 238. 9) Methyl 2-[fluoro(4-cyanophenyl)methyl]acrylate (3j) The obtained crude product was purified with hexane / ethyl acetate=18 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR(300MHz, CDCl3)δ:7.68(d,J=7.9Hz,2H),7.52(d,J=8.2Hz,2H),6.50(d,J=2.6Hz,1H),6.31(d,J=45.6Hz,1H),6.07(s,1H),3.73(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-175.98(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 218. 10) Methyl 2-{fluoro[(4-trifluoromethyl)phenyl]methyl}acrylate (3k) The obtained crude product was purified with hexane / ethyl acetate=30 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:7.64(d-like,J=7.9Hz,2H),7.52(d-like,J=7.9Hz,2H),6.49(s,1H),6.33(d,J=45.9Hz,1H),6.06(s,1H),3.74(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-63.23(s,3F),-174.79(d,J=44.8Hz,1F)ppm. 11) Methyl 4-[1-fluoro-(4-methoxycarbonylphenyl)methyl]acrylate (3l) The obtained crude product was purified with hexane / ethyl acetate=15 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR(300MHz,CDCl3)δ:8.04(d,J=7.9Hz,2H),7.46(d,J=7.9Hz,2H),6.47(d,J =2.4Hz,1H),6.32(d,J=45.9Hz,1H),6.03(s,1H),3.91(s,3H),3.72(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-174.43(d,J=46.6Hz,1F)ppm. MS(EI)m / z:[M] + 252. 12) Methyl 2-[fluoro(naphthyl-2-yl)methyl]acrylate (3m) The obtained crude product was purified with hexane / ethyl acetate=30 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:7.88-7.85(m,4H),7.53-7.48(m,3H),6.47(d,J=45.9Hz,2H),6.51(d,J=2.4Hz,1H),6.10(s,1H),3.72(s,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-171.15(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 244. 13) Methyl 2-[fluoro(cyclohexyl)methyl]acrylate (3n) The obtained crude product was purified with hexane / dichloromethane=3 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:6.38(s,1H),5.86(s,1H),5.12(dd,J=46.8,3.8Hz,1H),3.77(s,3H),1.75-1.63(m,6H),1.25-0.97(m,5H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-192.28(dd,J=46.6,24.1Hz,1F)ppm. MS(EI) m / z:[M-C6H 11 ] + 118. 14) Methyl 3-fluoro-2-methylene-5-phenylpentanoate (3o) The obtained crude product was purified with hexane / ethyl acetate=45 / 1 (vol / vol). 1 H-NMR(300MHz,CDCl3)δ:7.36-7.31(m,2H),7.26-7.24(m,3H),6.40(s,1H),6.01(s, 1H),5.37(dd,J=47.2,7.8Hz),3.80(s,3H),2.95-2.73(m,2H),2.33-1.93(m,2H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-186.47--186.82(m,1F)ppm. MS(EI) m / z:[M-HF] + 202, [M-HF-CO2H] + 143. 15)Ethyl 2-[fluoro(phenyl)methyl]acrylate (3p) The obtained crude product was purified with hexane / ethyl acetate=30 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:7.44-7.33(m,5H),6.46(d,J=2.6Hz,1H),6.29(d,J=45.9Hz,1H),6.02(s,1H),4.22-4.11(m,2H),1.23(t,J=7.1Hz,3H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-171.22(d,J=46.6Hz,1F)ppm. MS(EI)m / z:[M] + 208. 16) Ethyl 2-[fluoro(4-bromophenyl)methyl]acrylate (3q) The obtained crude product was purified with hexane / ethyl acetate=30 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR(300MHz,CDCl3)δ:7.50(d,J=8.2Hz,2H),7.27(d,J=6.5Hz,2H),6.45(d-like,J= 1.5Hz,1H),6.23(d,J=45.9Hz,1H),6.03(s,1H),4.22-4.11(m,2H),1.24(t,J=7.1Hz,3H ppm. 19 F-NMR(282MHz, CDCl3)δ:-172.31(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M] + 286. 17) tert-Butyl 2-[fluoro(phenyl)methyl]acrylate (3r) The obtained crude product was purified with hexane / ethyl acetate=45 / 1 (vol / vol). Colorless transparent liquid. 1H-NMR (300MHz, CDCl3)δ:7.37(brd,5H),6.39-6.37(m,1H),6.22(dd,J=46.3,1.0Hz,1H),5.97-5.94(m,1H),1.37(s,9H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-170.30(d,J=44.8Hz,1F)ppm. MS(EI)m / z:[M-tBu+H] + 180. 18) tert-Butyl 2-[fluoro(4-bromophenyl)methyl]acrylate (3s) The obtained crude product was purified with hexane / ethyl acetate=55 / 1 (vol / vol). Colorless transparent liquid. 1 H-NMR (300MHz, CDCl3)δ:7.50(d,J=7.9Hz,2H),7.25(d,J=5.0Hz,2H),6.37(s,1H),6.17(d,J=46.2Hz,1H),5.95(s,1H),1.39(s,9H)ppm. 19 F-NMR(282MHz, CDCl3)δ:-171.35(d,J=46.6Hz,1F)ppm. MS(EI)m / z:[M-tBu+H] + 258. [Industrial Applicability]

[0037] The 2-fluoromethylacrylic ester derivatives obtained by the method of the present invention are useful as production intermediates in the fields of medicines, agrochemicals, and electronic materials.

Claims

[Claim 1] The following general formula (1) 【Chemistry 7】 [In formula (1), R １ is a cyclohexyl group, a naphthyl-1-yl group, a naphthyl-2-yl group, a 2-phenylethyl group, or a group represented by the following general formula (2)] 【Chemistry 8】 (In formula (2), R ３ represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a cyano group, a trifluoromethyl group, or a methoxycarbonyl group, and R ２ represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group. The present invention relates to a method for producing a 2-hydroxymethylacrylic acid ester derivative represented by the following general formula (3): 【Chemistry 9】 [In formula (3), R １ is a cyclohexyl group, a naphthyl-1-yl group, a naphthyl-2-yl group, a 2-phenylethyl group, or a group represented by the following general formula (2)] 【Chemistry 10】 (In formula (2), R ３ represents a hydrogen atom, a methyl group, a halogen atom, a nitro group, a cyano group, a trifluoromethyl group, or a methoxycarbonyl group, and R ２ represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group. A method for producing a 2-fluoromethylacrylic ester derivative represented by the formula:

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