JP2011162521A - Arylsulfonyl[(hetero)aryl]methyl fluorides and method for production thereof - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide arylsulfonyl[(hetero)aryl]methyl fluorides and a method for efficient production thereof. <P>SOLUTION: There is provided a method for production of arylsulfonyl[(hetero)aryl]methyl fluorides (3) which are intermediates for producing (hetero)arylmethyl fluorides useful as medico-agrichemicals, functional materials or the like. The method includes reacting 2-arylsulfonyl-2-fluoroacetic ester derivatives with (hetero)aryl iodide derivatives in the presence of a copper salt and a base. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to arylsulfonyl [(hetero) aryl] methyl fluorides and a method for producing the same.

  It is disclosed that (hetero) arylmethyl fluorides are important compounds as medical and agricultural chemicals and functional materials and can be produced by desulfonylation reaction of arylsulfonyl [(hetero) aryl] methyl fluorides (non- Patent Document 1).

  As a method for producing the arylsulfonyl [(hetero) aryl] methyl fluorides, Non-Patent Document 1 discloses arylsulfonyl [(hetero) by reaction of o-trimethylsilylaryl triflate with 2-fluoro-2- (phenylsulfonyl) acetophenone. ) Aryl] methyl fluorides are disclosed. However, this method has poor selectivity of the introduction position of the aryl (fluoro) methyl group on the aromatic ring, and a benzoyl group is always introduced at the ortho position of the introduced fluoromethyl group. Moreover, since preparation of o-trimethylsilylaryl triflate is not easy, it cannot be said that it is an efficient method.

  A method for producing arylsulfonyl [(hetero) aryl] methyl fluorides utilizing the reaction of 2-arylsulfonyl-2-fluoroacetic acid ester derivatives of the present invention with (hetero) aryl iodide derivatives has been reported so far. Absent.

Journal of Organic Chemistry, 73, 5699-5713, 2008.

  The present invention provides a simple and efficient method for producing arylsulfonyl [(hetero) aryl] methyl fluorides, which are intermediates for the production of (hetero) arylmethyl fluorides useful as medicines and agricultural chemicals and functional materials. There is to do.

  As a result of intensive studies in view of the above problems, the present inventors have found that a coupling reaction between a 2-arylsulfonyl-2-fluoroacetic acid ester derivative and a (hetero) aryl iodide is efficient in the presence of a copper salt and a base. To give arylsulfonyl [(hetero) aryl] methyl fluorides, and completed the present invention. That is, the present invention relates to the general formula (3a)

(In the formula, Ar ¹ represents a phenyl group which may be substituted with an alkyl group having 1 to 4 carbon atoms, Ar ³ represents an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, carbon An alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, a phenyl group substituted with an alkoxy group having 1 to 4 carbon atoms or a cyano group; an alkyl group having 1 to 6 carbon atoms, a carbon number A naphthyl group optionally substituted by a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group; An alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy having 1 to 4 carbon atoms A pyridyl group optionally substituted by a group or a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, A quinolinyl group optionally substituted by a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms , An aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or an isoquinolinyl group optionally substituted by a cyano group; or an alkyl group having 1 to 6 carbon atoms, or an alkyl group having 1 to 6 carbon atoms Haloalkyl group, alkenyl group having 2 to 7 carbon atoms, aryl group having 6 to 10 carbon atoms, aralkyl group having 7 to 11 carbon atoms, halogen atom, 1 to 4 carbon atoms An arylsulfonyl [(hetero) aryl] methyl fluoride represented by the following formula:

  The present invention also provides a general formula (1)

(Wherein R represents an alkyl group having 1 to 4 carbon atoms, Ar ¹ represents the same meaning as described above), a 2-arylsulfonyl-2-fluoroacetic acid ester derivative represented by a copper salt and a base Below, general formula (2)

(In the formula, Ar ² represents an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, or 1 carbon atom. A phenyl group optionally substituted by an alkoxy group having 1 to 4 carbon atoms or a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, or 6 to 10 carbon atoms An aryl group, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or a naphthyl group optionally substituted by a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, and 2 to carbon atoms An alkenyl group having 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or a pyridyl group optionally substituted with a cyano group; Substituted with an alkyl group, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or a cyano group A good quinolinyl group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy having 1 to 4 carbon atoms An isoquinolinyl group optionally substituted by a group or a cyano group; or an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, or an aryl group having 6 to 10 carbon atoms Represents an aralkyl group having 7 to 11 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a pyrazolyl group optionally substituted with a cyano group. ) Represented by (wherein the reaction with hetero) aryl iodide derivative of the general formula (3)

(In the formula, Ar ¹ and Ar ² represent the same meaning as described above.) A method for producing arylsulfonyl [(hetero) aryl] methyl fluoride represented by

  INDUSTRIAL APPLICABILITY The present invention is effective as a method for efficiently producing arylsulfonyl [(hetero) aryl] methyl fluorides, which are intermediates for producing (hetero) arylmethyl fluorides useful as medicines and agricultural chemicals and functional materials.

  The present invention is described in detail below.

  The alkyl group having 1 to 4 carbon atoms represented by R may be linear, cyclic or branched, and may be a methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, A sec-butyl group, a tert-butyl group, a cyclopropyl group, a cyclopropylmethyl group and the like can be exemplified. R is preferably a tert-butyl group in terms of good yield.

The phenyl group represented by Ar ¹ may be substituted with an alkyl group having 1 to 4 carbon atoms. Specifically, phenyl group, p-tolyl group, m-tolyl group, o-tolyl group, 2,4-dimethylphenyl group, 3,5-dimethylphenyl group, mesityl group, 4-propylphenyl group, 4- Examples thereof include a butylphenyl group and a 4-tert-butylphenyl group. Ar ¹ is preferably a phenyl group in terms of good yield.

The phenyl group represented by Ar ² is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, carbon It may be substituted with an alkoxy group of formula 1 to 4 or a cyano group. Specifically, phenyl group, p-tolyl group, m-tolyl group, o-tolyl group, 2,4-dimethylphenyl group, 3,5-dimethylphenyl group, mesityl group, 2-ethylphenyl group, 3- Ethylphenyl group, 4-ethylphenyl group, 2,4-diethylphenyl group, 3,5-diethylphenyl group, 2-propylphenyl group, 4-propylphenyl group, 2-isopropylphenyl group, 2,4-diisopropylphenyl Group, 4-butylphenyl group, 4-tert-butylphenyl group, 2,4-di-tert-butylphenyl group, 4-pentylphenyl group, 4-hexylphenyl group, 2-fluorophenyl group, 3-fluorophenyl Group, 4-fluorophenyl group, 2,3-difluorophenyl group, 2,4-difluorophenyl group, 3,4-difluorophenyl 3,5-difluorophenyl group, 2,3,4,5,6-pentafluorophenyl group, 2,3-difluoro-4-propylphenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group, 4-fluoro-3-methylphenyl group, 4-fluoro-2-methyl Phenyl group, 2-fluoro-3-methylphenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 2-vinylphenyl group, 3-vinylphenyl group, 4 -Vinylphenyl group, 2-allylphenyl group, 3-allylphenyl group, 4-allylphenyl group, 2-methoxy Phenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 4-ethoxyphenyl group, 4-ethoxy-2,3-difluorophenyl group, 2,3- (methylenedioxy) phenyl group, 3,4- ( Methylenedioxy) phenyl group, 2-biphenylyl group, 3-biphenylyl group, 4-biphenylyl group, 2-cyanophenyl group, 3-cyanophenyl group, 4-cyanophenyl group and the like can be exemplified.

Ar ³ is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, or an alkoxy having 1 to 4 carbon atoms. Or a phenyl group substituted with a cyano group. Specifically, p-tolyl group, m-tolyl group, o-tolyl group, 2,4-dimethylphenyl group, 3,5-dimethylphenyl group, mesityl group, 2-ethylphenyl group, 3-ethylphenyl group 4-ethylphenyl group, 2,4-diethylphenyl group, 3,5-diethylphenyl group, 2-propylphenyl group, 4-propylphenyl group, 2-isopropylphenyl group, 2,4-diisopropylphenyl group, 4 -Butylphenyl group, 4-tert-butylphenyl group, 2,4-di-tert-butylphenyl group, 4-pentylphenyl group, 4-hexylphenyl group, 2-fluorophenyl group, 3-fluorophenyl group, 4 -Fluorophenyl group, 2,3-difluorophenyl group, 2,4-difluorophenyl group, 3,4-difluorophenyl group, 3,5- Fluorophenyl group, 2,3,4,5,6-pentafluorophenyl group, 2,3-difluoro-4-propylphenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 3,4- Dichlorophenyl group, 3,5-dichlorophenyl group, 2-bromophenyl group, 3-bromophenyl group, 4-bromophenyl group, 4-fluoro-3-methylphenyl group, 4-fluoro-2-methylphenyl group, 2- Fluoro-3-methylphenyl group, 2-trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 2-vinylphenyl group, 3-vinylphenyl group, 4-vinylphenyl group, 2-allylphenyl group, 3-allylphenyl group, 4-allylphenyl group, 2-methoxyphenyl group, -Methoxyphenyl group, 4-methoxyphenyl group, 4-ethoxyphenyl group, 4-ethoxy-2,3-difluorophenyl group, 2,3- (methylenedioxy) phenyl group, 3,4- (methylenedioxy) Examples thereof include a phenyl group, 2-biphenylyl group, 3-biphenylyl group, 4-biphenylyl group, 2-cyanophenyl group, 3-cyanophenyl group, 4-cyanophenyl group and the like.

The naphthyl group represented by Ar ² and Ar ³ is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, It may be substituted with an atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group. Specifically, 1-naphthyl group, 2-naphthyl group, 2-methyl-1-naphthyl group, 1-methyl-2-naphthyl group, 1,2-dimethyl-3-naphthyl group, 2-ethyl-1- Naphthyl group, 3-ethyl-1-naphthyl group, 4-ethyl-1-naphthyl group, 2,4-diethyl-1-naphthyl group, 4-tert-butyl-1-naphthyl group, 2,4-di-tert -Butyl-1-naphthyl group, 2-fluoro-1-naphthyl group, 1-fluoro-2-naphthyl group, 3-fluoro-1-naphthyl group, 4-fluoro-1-naphthyl group, 2,3-difluoro- 1-naphthyl group, 2,4-difluoro-1-naphthyl group, 3,4-difluoro-1-naphthyl group, 3,5-difluoro-1-naphthyl group, 2,3,4,5,6,7, 8-heptafluoro-1-naphthyl group, 2-c B-1-Naphtyl group, 3-chloro-1-naphthyl group, 4-chloro-1-naphthyl group, 3,4-dichloro-1-naphthyl group, 3,5-dichloro-1-naphthyl group, 3-bromo -1-naphthyl group, 4-bromo-1-naphthyl group, 2-trifluoromethyl-1-naphthyl group, 3-trifluoromethyl-1-naphthyl group, 4-trifluoromethyl-1-naphthyl group, 2- Vinyl-1-naphthyl group, 3-vinyl-1-naphthyl group, 4-vinyl-1-naphthyl group, 2-allyl-1-naphthyl group, 3-allyl-1-naphthyl group, 4-allyl-1-naphthyl group Group, 2-methoxy-1-naphthyl group, 3-methoxy-1-naphthyl group, 4-methoxy-1-naphthyl group, 4-ethoxy-1-naphthyl group, 4-ethoxy-2,3-difluoro-1- Naphthyl group, 2, 3 (Methylenedioxy) -1-naphthyl group, 3,4- (methylenedioxy) -1-naphthyl group, 2-phenyl-1-naphthyl group, 3-phenyl-1-naphthyl group, 4-phenyl-1- Examples include a naphthyl group, 2-cyano-1-naphthyl group, 3-cyano-1-naphthyl group, 4-cyano-1-naphthyl group, and the like.

The pyridyl group represented by Ar ² and Ar ³ is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, It may be substituted with an atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group. Specifically, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 3-methyl-2-pyridyl group, 2-methyl-3-pyridyl group, 4-methyl-2-pyridyl group, 4-methyl -3-pyridyl group, 2,5-dimethyl-4-pyridyl group, 4-tert-butyl-2-pyridyl group, 2,4-di-tert-butyl-3-pyridyl group, 4-pentyl-2-pyridyl group Group, 2-fluoro-3-pyridyl group, 3-fluoro-2-pyridyl group, 4-fluoro-2-pyridyl group, 2,3-difluoro-4-pyridyl group, 2,4-difluoro-3-pyridyl group 3,4-difluoro-2-pyridyl group, 3,5-difluoro-4-pyridyl group, 3,4,5,6-tetrafluoro-2-pyridyl group, 2-chloro-3-pyridyl group, 3- Chloro-2-pyridyl group, 4-chloro 2-pyridyl group, 3,4-dichloro-2-pyridyl group, 3,5-dichloro-4-pyridyl group, 3-bromo-2-pyridyl group, 4-bromo-2-pyridyl group, 3-trifluoro Methyl-2-pyridyl group, 2-trifluoromethyl-4-pyridyl group, 4-trifluoromethyl-2-pyridyl group, 2-vinyl-3-pyridyl group, 3-vinyl-2-pyridyl group, 4-vinyl 2-pyridyl group, 2-allyl-3-pyridyl group, 3-allyl-2-pyridyl group, 4-allyl-2-pyridyl group, 2-methoxy-3-pyridyl group, 3-methoxy-2-pyridyl group 4-methoxy-2-pyridyl group, 2-phenyl-3-pyridyl group, 3-phenyl-2-pyridyl group, 4-phenyl-2-pyridyl group, 2-cyano-3-pyridyl group, 3-cyano- 2-pyridyl group It can be exemplified 4-cyano-2-pyridyl group.

The quinolinyl group represented by Ar ² and Ar ³ is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, It may be substituted with an atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group. Specifically, 2-quinolinyl group, 3-quinolinyl group, 4-quinolinyl group, 5-quinolinyl group, 6-quinolinyl group, 7-quinolinyl group, 8-quinolinyl group, 3-methyl-2-quinolinyl group, 4 -Methyl-3-quinolinyl group, 5-methyl-2-quinolinyl group, 4-methyl-2-quinolinyl group, 2,4-dimethyl-3-quinolinyl group, 4-tert-butyl-2-quinolinyl group, 3, 4-di-tert-butyl-2-quinolinyl group, 4-pentyl-2-quinolinyl group, 2-fluoro-3-quinolinyl group, 3-fluoro-2-quinolinyl group, 4-fluoro-2-quinolinyl group, 3 , 4-difluoro-2-quinolinyl group, 2,4-difluoro-3-quinolinyl group, 2,3-difluoro-4-quinolinyl group, 3,5-difluoro-2-quinolinyl group, 3, , 5,6,7,8-hexafluoro-2-quinolinyl group, 3-chloro-2-quinolinyl group, 2-chloro-3-quinolinyl group, 4-chloro-2-quinolinyl group, 3,4-dichloro- 2-quinolinyl group, 3,5-dichloro-2-quinolinyl group, 3-bromo-2-quinolinyl group, 4-bromo-2-quinolinyl group, 3-trifluoromethyl-2-quinolinyl group, 4-trifluoromethyl 2-quinolinyl group, 4-trifluoromethyl-3-quinolinyl group, 2-vinyl-3-quinolinyl group, 3-vinyl-2-quinolinyl group, 4-vinyl-2-quinolinyl group, 2-allyl-3- Quinolinyl group, 3-allyl-2-quinolinyl group, 4-allyl-2-quinolinyl group, 2-methoxy-3-quinolinyl group, 3-methoxy-2-quinolinyl group, 4-methoxy-2-alkyl group Linyl group, 2-phenyl-3-quinolinyl group, 3-phenyl-2-quinolinyl group, 4-phenyl-2-quinolinyl group, 3-cyano-2-quinolinyl group, 2-cyano-3-quinolinyl group, 4- A cyano-2-quinolinyl group and the like can be exemplified.

The isoquinolinyl group represented by Ar ² and Ar ³ is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, It may be substituted with an atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group. Specifically, 1-isoquinolinyl group, 3-isoquinolinyl group, 4-isoquinolinyl group, 5-isoquinolinyl group, 6-isoquinolinyl group, 7-isoquinolinyl group, 8-isoquinolinyl group, 3-methyl-1-isoquinolinyl group, 1 -Methyl-3-isoquinolinyl group, 4-methyl-1-isoquinolinyl group, 4-methyl-1-isoquinolinyl group, 1,4-dimethyl-3-isoquinolinyl group, 4-tert-butyl-1-isoquinolinyl group, 3, 4-di-tert-butyl-1-isoquinolinyl group, 4-pentyl-1-isoquinolinyl group, 1-fluoro-3-isoquinolinyl group, 3-fluoro-1-isoquinolinyl group, 4-fluoro-1-isoquinolinyl group, 3 , 4-difluoro-1-isoquinolinyl group, 1,4-difluoro-3-isoquinolinyl group, , 3-difluoro-4-isoquinolinyl group, 3,5-difluoro-1-isoquinolinyl group, 3,4,5,6,7,8-hexafluoro-1-isoquinolinyl group, 3-chloro-1-isoquinolinyl group, 1-chloro-3-isoquinolinyl group, 4-chloro-1-isoquinolinyl group, 3,4-dichloro-1-isoquinolinyl group, 3,5-dichloro-1-isoquinolinyl group, 3-bromo-1-isoquinolinyl group, 4 -Bromo-1-isoquinolinyl group, 3-trifluoromethyl-1-isoquinolinyl group, 1-trifluoromethyl-1-isoquinolinyl group, 4-trifluoromethyl-1-isoquinolinyl group, 1-vinyl-3-isoquinolinyl group, 3-vinyl-1-isoquinolinyl group, 4-vinyl-1-isoquinolinyl group, 1-allyl-3-isoquinolinyl 3-allyl-1-isoquinolinyl group, 4-allyl-1-isoquinolinyl group, 1-methoxy-3-isoquinolinyl group, 3-methoxy-1-isoquinolinyl group, 4-methoxy-1-isoquinolinyl group, 1-phenyl- 3-isoquinolinyl group, 3-phenyl-1-isoquinolinyl group, 4-phenyl-1-isoquinolinyl group, 3-cyano-1-isoquinolinyl group, 1-cyano-3-isoquinolinyl group, 4-cyano-1-isoquinolinyl group, etc. Can be illustrated.

The pyrazolyl group represented by Ar ² and Ar ³ is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, carbon It may be substituted with an aralkyl group having 7 to 11 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group. Specifically, 1H-3-pyrazolyl group, 1H-4-pyrazolyl group, 1H-5-pyrazolyl group, 1-methyl-1H-3-pyrazolyl group, 1-methyl-1H-4-pyrazolyl group, 1- Methyl-1H-5-pyrazolyl group, 1,3-dimethyl-1H-4-pyrazolyl group, 1,4-dimethyl-1H-3-pyrazolyl group, 1,5-dimethyl-1H-3-pyrazolyl group, 1, 5-dimethyl-1H-4-pyrazolyl group, 4-tert-butyl-1-methyl-1H-3-pyrazolyl group, 1-methyl-4-pentyl-1H-3-pyrazolyl group, 3-fluoro-1-methyl -1H-4-pyrazolyl group, 3-fluoro-1-methyl-1H-5-pyrazolyl group, 4-fluoro-1-methyl-1H-3-pyrazolyl group, 4-fluoro-1-methyl-1H-5 Pyrazolyl group 5-fluoro-1-methyl-1H-3-pyrazolyl group, 5-fluoro-1-methyl-1H-4-pyrazolyl group, 3,4-difluoro-1-methyl-1H-5-pyrazolyl group, 4,5 -Difluoro-1-methyl-1H-3-pyrazolyl group, 3-chloro-1-methyl-1H-4-pyrazolyl group, 3-chloro-1-methyl-1H-5-pyrazolyl group, 4-chloro-1- Methyl-1H-3-pyrazolyl group, 4-chloro-1-methyl-1H-5-pyrazolyl group, 5-chloro-1-methyl-1H-3-pyrazolyl group, 5-chloro-1-methyl-1H-4 -Pyrazolyl group, 3,4-dichloro-1-methyl-1H-5-pyrazolyl group, 4,5-dichloro-1-methyl-1H-3-pyrazolyl group, 3-bromo-1-methyl-1H-4- Pyrazolyl group, 3-bromide -1-methyl-1H-5-pyrazolyl group, 4-bromo-1-methyl-1H-3-pyrazolyl group, 4-bromo-1-methyl-1H-5-pyrazolyl group, 5-bromo-1-methyl- 1H-3-pyrazolyl group, 5-bromo-1-methyl-1H-4-pyrazolyl group, 3,4-dibromo-1-methyl-1H-5-pyrazolyl group, 4,5-dibromo-1-methyl-1H -3-pyrazolyl group, 1-methyl-3-trifluoromethyl-1H-4-pyrazolyl group, 1-methyl-3-trifluoromethyl-1H-5-pyrazolyl group, 1-methyl-4-trifluoromethyl- 1H-3-pyrazolyl group, 1-methyl-4-trifluoromethyl-1H-5-pyrazolyl group, 1-methyl-5-trifluoromethyl-1H-3-pyrazolyl group, 4-methyl-3-trifluoro Methyl-1H-5-pyrazolyl group, 1-methyl-3-vinyl-1H-5-pyrazolyl group, 3-allyl-1-methyl-1H-5-pyrazolyl group, 3-methoxy-1-methyl-1H-5 -Pyrazolyl group, 1-methyl-3-phenyl-1H-5-pyrazolyl group, 3-cyano-1-methyl-1H-5-pyrazolyl group, 1-benzyl-1H-3-pyrazolyl group, 1-benzyl-1H -4-pyrazolyl group, 1-benzyl-1H-5-pyrazolyl group, 1-benzyl-3-methyl-1H-4-pyrazolyl group, 1-benzyl-4-methyl-1H-3-pyrazolyl group, 1-benzyl -1H-3-pyrazolyl group, 1-benzyl-5-dimethyl-1H-4-pyrazolyl group, 1-benzyl-4-tert-butyl-1H-3-pyrazolyl group, 1-benzyl-3-fluoro 1H-4-pyrazolyl group, 1-benzyl-3-fluoro-1H-5-pyrazolyl group, 1-benzyl-4-fluoro-1H-3-pyrazolyl group, 1-benzyl-4-fluoro-1H-5-pyrazolyl 1-benzyl-5-fluoro-1H-3-pyrazolyl group, 1-benzyl-5-fluoro-1H-4-pyrazolyl group, 1-benzyl-3-trifluoromethyl-1H-4-pyrazolyl group, 1 -Benzyl-3-trifluoromethyl-1H-5-pyrazolyl group, 1-benzyl-4-trifluoromethyl-1H-3-pyrazolyl group, 1-benzyl-4-trifluoromethyl-1H-5-pyrazolyl group, Examples include 1-benzyl-5-trifluoromethyl-1H-3-pyrazolyl group, 1-benzyl-3-trifluoromethyl-1H-5-pyrazolyl group and the like. It is possible.

  Next, the production method of the arylsulfonyl [(hetero) aryl] methyl fluorides (3) of the present invention will be described in detail.

(In the formula, R, Ar ¹ and Ar ² represent the same meaning as described above.)
The 2-arylsulfonyl-2-fluoroacetic acid ester derivative (1) which is a raw material of the present invention can be prepared by a method described in the literature (Japanese Patent Laid-Open No. 62-207230) or a method analogous thereto.

  The (hetero) aryl iodide derivative (2), which is the raw material of the present invention, is partially commercially available, but is described in the literature (Comprehensive Organic Transformations 2nd. Ed., RC Larock, John Wiley & Sons, Inc, pp 607-751. .)) Or a method analogous thereto.

  Examples of the copper salt that can be used in the present invention include copper (I) chloride, copper (I) bromide, copper (I) bromide dimethyl sulfide complex, copper (I) iodide, copper (I) cyanide, trifluoro. Examples thereof include copper (I) lomethanesulfonate. From the viewpoint of good yield, it is preferable to use copper (I) iodide.

  These copper salts may be used alone, but a ligand may be further added. Examples of ligands that can be used include 2-picolinic acid, 2,6-pyridinedicarboxylic acid, 2,6-bis (4-phenyl-4,5-dihydrooxazol-2-yl) pyridine, and 2- (N , N-dimethylaminomethyl) pyridine, 2- (N, N-dimethylaminomethyl) -6-methylpyridine, pyridine derivatives such as 2,6-bis (N, N-dimethylaminomethyl) pyridine, quinoline, isoquinoline, Examples include quinoline derivatives such as 8-hydroxyquinoline, tertiary amines such as N-hydroxyethyl-N, N-dimethylamine and N, N, N ′, N′-tetramethylethylenediamine. In view of good yield, 2-picolinic acid is preferably used.

  Examples of the base that can be used in the present invention include metal alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide, alkyllithiums such as butyllithium, sec-butyllithium and tert-butyllithium, lithium diisopropylamide, lithium Metal amides such as 2,2,6,6-tetramethylpiperazide, lithium hexamethyldisilazide, potassium hexamethyldisilazide and sodium hexamethyldisilazide, metal hydrogens such as sodium hydride and potassium hydride Inorganic salts such as compound, sodium hydroxide, potassium hydroxide and potassium carbonate can be exemplified. From the viewpoint of good yield, it is preferable to use potassium t-butoxide.

  The solvent that can be used in this reaction may be any solvent that does not inhibit the reaction. Specifically, tetrahydrofuran, diethyl ether, 1,4-dioxane, methyl-tert-butyl ether, 1,2-dimethoxyethane, Ether solvents such as cyclopentyl methyl ether, hydrocarbon solvents such as hexane, pentane and cyclohexane, aromatic hydrocarbon solvents such as benzene, toluene and xylene, dimethyl sulfoxide, N, N-dimethylformamide, N-methyl-2 -Pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone, methanol, ethanol, water, etc. can be exemplified, and two or more of these solvents are mixed. Can be used. It is preferable to use dimethyl sulfoxide in terms of a good yield in the reaction.

  The molar ratio of the 2-arylsulfonyl-2-fluoroacetic acid ester derivative (1) and the (hetero) aryl iodide derivative (2) is preferably 3: 1 to 1: 1, and 2: 1 in terms of good yield. To 1: 1 is more preferred.

  The molar ratio of the 2-arylsulfonyl-2-fluoroacetic acid ester derivative (1) and the copper salt is preferably 1: 1 to 1: 0.01, and 1: 0.2 to 1: 0 in terms of good yield. .01 is more preferred.

  The molar ratio of the 2-arylsulfonyl-2-fluoroacetic acid ester derivative (1) to the ligand is preferably 1: 1 to 1: 0.01, and 1: 0.2 to 1: 0.01 is more preferable.

  The molar ratio of the 2-arylsulfonyl-2-fluoroacetic acid ester derivative (1) and the base is preferably 1: 1 to 1: 5, and more preferably 1: 1 to 1: 2 in terms of good yield.

The reaction temperature can be carried out at a temperature appropriately selected from the range of 0 ° C to 100 ° C. The range from 20 ° C. to 80 ° C. is preferable in terms of good yield.
The reaction can be performed at a pressure appropriately selected from the range of atmospheric pressure (0.1 MPa) to 1.0 MPa, but the reaction proceeds sufficiently even at atmospheric pressure. The atmosphere during the reaction may be an inert gas such as argon or nitrogen, but proceeds sufficiently even in air.
The reaction may give 2-arylsulfonyl-2-fluoro-2- (hetero) aryl acetate derivative (4) as a by-product together with arylsulfonyl [(hetero) aryl] methyl fluorides (3) . There are no particular limitations on the post-treatment method of the reaction, but the formation of by-products is suppressed, and the yield of arylsulfonyl [(hetero) aryl] methyl fluorides (3) is good. In the presence of a Bronsted acid such as sulfuric acid or trifluoroacetic acid, or an inorganic base such as an aqueous solution of sodium hydrogen carbonate, an aqueous solution of sodium hydroxide or an aqueous solution of potassium hydroxide, heating at a temperature appropriately selected from the range of 30 ° C to 80 ° C Is preferred.
The method for isolating the target product from the solution after the reaction is not particularly limited, but may be a general method such as solvent extraction, column chromatography, preparative thin layer chromatography, preparative liquid chromatography, recrystallization or sublimation. The object can be obtained.

EXAMPLES Next, although an Example demonstrates this invention in detail, this invention is not limited to these.
Example-1

To a dimethyl sulfoxide solution (1.0 mL) of methyl 2-fluoro-2-phenylsulfonylacetate (232 mg, 1.0 mmol) at room temperature under an argon atmosphere, copper iodide (9.5 mg, 0.050 mmol), 2- Add picolinic acid (6.2 mg, 0.050 mmol), triethylamine (0.21 mL, 1.5 mmol), 1-iodo-4- (trifluoromethyl) benzene (0.073 mL, 0.50 mmol) and add to 70 ° C. And stirred for 12 hours. A saturated aqueous ammonium chloride solution (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1- [fluoro (phenylsulfonyl) methyl] -4- (trifluoro Methyl) benzene (70.9 mg, 45% yield) was obtained as a white solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81 (brd, J = 8.2 Hz, 2H), 7.72 (brt, J = 7.5 Hz, 1H), 7.66 (d, J = 8. 5Hz, 2H), 7.56 (brdd, J = 8.2, 7.5Hz, 2H), 7.52 (d, J = 8.5Hz, 2H), 6.12 (d, J = 46Hz, 1H) ). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-63.0 (s, 3F), -177.0 (s, 1F).
Example-2

To a dimethyl sulfoxide solution (1.0 mL) of 1-iodo-4- (trifluoromethyl) benzene (136 mg, 0.50 mmol) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate ( 274 mg, 1.0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol), potassium tert-butoxide (112 mg, 1.0 mmol) were added, and 70 ° C. For 12 hours. A saturated aqueous ammonium chloride solution (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 2-fluoro-2-phenylsulfonyl-2- [4- (tri Fluoromethyl) phenyl] tert-butyl acetate (131 mg, 63% yield) as a white yellow solid and 1- [fluoro (phenylsulfonyl) methyl] -4- (trifluoromethyl) benzene (43.4 mg, yield) 28%) as white solids, respectively. 2-fluoro-2-phenylsulfonyl-2- [4- (trifluoromethyl) phenyl] tert-butyl acetate: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.85 (d, J = 8.3 Hz, 2H) , 7.73-7.64 (m, 5H), 7.50 (brdd, J = 8.3, 7.6 Hz, 2H), 1.49 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-63.3 (s, 3F), -154.2 (s, 1F).
Example-3

To a dimethyl sulfoxide solution (1.0 mL) of 1-iodo-4- (trifluoromethyl) benzene (136 mg, 0.50 mmol) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate ( 274 mg, 1.0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol), potassium tert-butoxide (112 mg, 1.0 mmol) were added, and 70 ° C. For 12 hours. GC analysis of tert-butyl 2-fluoro-2-phenylsulfonyl-2- [4- (trifluoromethyl) phenyl] acetate and 1- [fluoro (phenylsulfonyl) methyl] -4- (trifluoromethyl) benzene It was confirmed that a mixture was obtained. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 1 hr, 1 M hydrochloric acid (3.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1- [fluoro (phenylsulfonyl) methyl] -4- (trifluoro Methyl) benzene (124 mg, 79% yield) was obtained as a white solid.
Example-4

To a dimethyl sulfoxide solution (1.0 mL) of iodobenzene (102 mg, 0.50 mmol), tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), copper iodide at room temperature under an argon atmosphere. (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 70 ° C. for 12 hours. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 2 hr. 1 M hydrochloric acid (2.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to obtain [fluoro (phenylsulfonyl) methyl] benzene (97.5 mg, yield). 78%) was obtained as a white yellow solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.79 (brd, J = 8.1 Hz, 2H), 7.69 (brt, J = 7.5 Hz, 1H), 7.53 (brdd, J = 8. 1, 7.5 Hz, 2H), 7.47-7.43 (m, 1H), 7.40-7.34 (m, 4H), 6.06 (d, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-175.8 (s, 1F).
Example-5

To a solution of 1-bromo-4-iodobenzene (144 mg, 0.50 mmol) in dimethyl sulfoxide (1.0 mL) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1. 0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 70 ° C. for 12 hours. Stir. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 2 hr. 1 M hydrochloric acid (1.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1-bromo-4- [fluoro (phenylsulfonyl) methyl] benzene ( 130 mg, 79% yield) was obtained as a white yellow solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81 (brd, J = 8.1 Hz, 2H), 7.71 (brt, J = 7.5 Hz, 1H), 7.58-7.52 (m, 4H), 7.24 (d, J = 8.7 Hz, 2H), 6.02 (d, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-176.0 (s, 1F).
Example-6

To a dimethyl sulfoxide solution (1.0 mL) of 1-fluoro-4-iodobenzene (111 mg, 0.50 mmol) was added tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1. 0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 70 ° C. for 12 hours. Stir. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 2 hr. 1 M hydrochloric acid (1.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1-fluoro-4- [fluoro (phenylsulfonyl) methyl] benzene ( 89.8 mg, 67% yield) as brown crystals, and 2-fluoro-2- [4-fluorophenyl] -2-phenylsulfonylacetic acid tert-butyl acetate (14.7 mg, 8% yield) as a yellow viscous body Got as. 1-fluoro-4- [fluoro (phenylsulfonyl) methyl] benzene: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81 (brd, J = 8.2 Hz, 2H), 7.71 (brt, J = 7 .5Hz, 1H), 7.55 (brdd, J = 8.2, 7.5Hz, 2H), 7.37 (dd, J = 8.4, 5.2Hz, 2H), 7.08 (dd, J = 8.4, 8.4 Hz, 2H), 6.04 (d, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-109.0 (s, 1F), -174.4 (s, 1F). 2-Fluoro-2- [4-fluorophenyl] -2-phenylsulfonyl acetate tert-butyl: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.72-7.64 (m, 4H), 7.57 (brt , J = 8.1 Hz, 1H), 7.48 (brdd, J = 8.1, 8.1 Hz, 2H), 7.07 (dd, J = 8.5, 8.5 Hz, 2H), 1. 50 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-109.9 (s, 1F), -153.2 (s, 1F).
Example-7

To a solution of 4-iodoanisole (119 mg, 0.50 mmol) in dimethyl sulfoxide (1.0 mL) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 90 ° C. for 12 hours. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 4 hr, 1 M hydrochloric acid (2.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 4- [fluoro (phenylsulfonyl) methyl] anisole (75.4 mg, Yield 54%) was obtained as a white yellow solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.82 (brd, J = 8.0 Hz, 2H), 7.69 (brt, J = 7.5 Hz, 1H), 7.55 (brdd, J = 8. 0, 7.5 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 6.90 (d, J = 8.3 Hz, 2H), 6.00 (d, J = 45 Hz, 1H) ), 3.83 (s, 3H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-172.9 (s, 1F).
Example-8

To a dimethyl sulfoxide solution (1.0 mL) of 1-chloro-4-iodobenzene (119 mg, 0.50 mmol) at room temperature in an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1. 0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 100 ° C. for 12 hours. Stir. A saturated aqueous ammonium chloride solution (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1-chloro-4- [fluoro (phenylsulfonyl) methyl] benzene ( 130 mg, 91% yield) was obtained as a white yellow solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81 (brd, J = 8.2 Hz, 2H), 7.71 (brt, J = 7.5 Hz, 1H), 7.56 (brdd, 8.2) 7.5 Hz, 2H), 7.37 (brd, J = 8.3 Hz, 2H), 7.31 (brd, J = 8.3 Hz, 2H), 6.04 (d, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-175.7 (s, 1F).
Example-9

To a dimethyl sulfoxide solution (1.0 mL) of 1-iodo-3- (trifluoromethyl) benzene (136 mg, 0.50 mmol) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate ( 274 mg, 1.0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol), potassium tert-butoxide (112 mg, 1.0 mmol) were added, and 70 ° C. For 12 hours. 1M aqueous potassium hydroxide solution (2.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 4 hr. 1 M hydrochloric acid (2.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (4: 1)] to give 1- [fluoro (phenylsulfonyl) methyl] -3- (trifluoro Methyl) benzene (121 mg, 76% yield) as a white yellow solid, and tert-butyl 2-fluoro-2-phenylsulfonyl-2- [3- (trifluoromethyl) phenyl] acetate (24.2 mg, yield) 12%) was obtained as a yellow viscous body. 1- [Fluoro (phenylsulfonyl) methyl] -3- (trifluoromethyl) benzene: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.78 (brd, J = 8.2 Hz, 2H), 7.74-7 .70 (m, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.57-7.53 (m, 3H), 7.50 (brs, 1H), 6.12 (d , J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-62.9 (s, 3F), -176.6 (s, 1F). 2-Fluoro-2-phenylsulfonyl-2- [3- (trifluoromethyl) phenyl] tert-butyl acetate: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.96 (brd, J = 8.0 Hz, 2H) 7.88 (brs, 1H), 7.73-7.68 (m, 3H), 7.59 (brt, J = 8.1 Hz, 1H), 7.55 (brdd, J = 8.0, 7.9 Hz, 1H), 7.49 (brdd, J = 8.1, 7.5 Hz, 2H), 1.51 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-62.9 (s, 3F), -154.3 (s, 1F).
Example-10

To a dimethyl sulfoxide solution (1.0 mL) of 4-iodobenzonitrile (119 mg, 0.50 mmol) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), Copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 70 ° C. for 12 hours. 1M aqueous potassium hydroxide solution (2.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 4 hr. 1 M hydrochloric acid (2.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 4- [fluoro (phenylsulfonyl) methyl] benzonitrile (113 mg, yield). 82%) was obtained as a pale orange solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.80 (brd, J = 8.1 Hz, 2H), 7.73 (brt, J = 7.5 Hz, 1H), 7.69 (brd, J = 8. 1 Hz, 2H), 7.57 (brdd, J = 8.1, 7.5 Hz, 2H), 7.51 (brd, J = 8.1 Hz, 2H), 6.11 (d, J = 46 Hz, 1H) ). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-177.7 (s, 1F).
Example-11

To a dimethyl sulfoxide solution (1.0 mL) of 3-iodopyridine (103 mg, 0.50 mmol) at room temperature in an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 70 ° C. for 12 hours. GC confirmed that a mixture of 3- [fluoro (phenylsulfonyl) methyl] pyridine and 2-fluoro-2-phenylsulfonyl-3-pyridyl acetate tert-butyl was obtained. 1M aqueous potassium hydroxide solution (2.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 4 hr. 1 M hydrochloric acid (2.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (1: 1)] to give 3- [fluoro (phenylsulfonyl) methyl] pyridine (54.0 mg, Yield 43%) was obtained as brown crystals. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.72 (brs, 1H), 8.58 (brs, 1H), 7.83 (brd, J = 8.2 Hz, 2H), 7.77-7.71 (M, 2H), 7.57 (brdd, J = 8.2, 7.5 Hz, 2H), 7.37-7.34 (m, 1H), 6.10 (d, J = 46 Hz, 1H) . ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-178.4 (s, 1F).
Example-12

To a dimethyl sulfoxide solution (1.0 mL) of 3-iodopyridine (103 mg, 0.50 mmol) at room temperature in an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 100 ° C. for 12 hours. Water (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (1: 1)] to give 3- [fluoro (phenylsulfonyl) methyl] pyridine (26.4 mg, Yield 21%) was obtained as a brown crystalline substance, and 2-fluoro-2-phenylsulfonyl-3-pyridyl acetate tert-butyl acetate (57.9 mg, 33% yield) was obtained as a brown viscous body. 2-Fluoro-2-phenylsulfonyl-3-pyridyl acetate tert-butyl: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.82 (brs, 1H), 8.70 (brs, 1H), 8.10 (brd , J = 8.2 Hz, 1H), 7.73-7.67 (m, 3H), 7.50 (brdd, J = 8.2, 7.5 Hz, 2H), 7.37-7.34 ( m, 1H), 1.51 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-156.4 (s, 1F).
Example-13

To a solution of 1-fluoro-3-iodobenzene (111 mg, 0.50 mmol) in dimethyl sulfoxide (1.0 mL) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1. 0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 70 ° C. for 12 hours. Stir. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 2 hr. 1 M hydrochloric acid (1.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1-fluoro-3- [fluoro (phenylsulfonyl) methyl] benzene ( 81.7 mg, 61% yield) as a white yellow solid and tert-butyl 2-fluoro-2- (3-fluorophenyl) -2-phenylsulfonylacetate (16.6 mg, 9% yield) as a yellow viscous body Got as. 1-fluoro-3- [fluoro (phenylsulfonyl) methyl] benzene: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.80 (brd, J = 8.1 Hz, 2H), 7.71 (brt, J = 7 .5Hz, 1H), 7.55 (brdd, J = 8.1, 7.5Hz, 2H), 7.37 (m, 1H), 7.20-7.13 (m, 2H), 7.06 (Brd, J = 9.2 Hz, 1H), 6.05 (d, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-111.5 (s, 1F), -175.9 (s, 1F). 2-Fluoro-2- (3-fluorophenyl) -2-phenylsulfonyl acetate tert-butyl: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.72 (brd, J = 8.3 Hz, 2H), 7.67 (Brt, J = 7.5 Hz, 1H), 7.48 (brdd, J = 8.3, 7.5 Hz, 2H), 7.41 (brd, J = 9.9 Hz, 1H), 7.38- 7.33 (m, 1H), 7.18-7.13 (m, 2H), 1.51 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-111.5 (s, 1F), -153.3 (s, 1F).
Example-14

To a dimethyl sulfoxide solution (1.0 mL) of 2-iodopyridine (103 mg, 0.50 mmol), tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine at room temperature under an argon atmosphere. Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 70 ° C. for 12 hours. 1M aqueous potassium hydroxide solution (2.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 4 hr. 1 M hydrochloric acid (2.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (1: 1)] to give 2- [fluoro (phenylsulfonyl) methyl] pyridine (54.0 mg, Yield 43%) was obtained as brown crystals. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.67 (d, J = 4.8 Hz, 1H), 7.90 (brd, J = 8.1 Hz, 2H), 7.77 (ddd, J = 7. 7, 7.7, 1.7 Hz, 1H), 7.72 (brt, J = 7.5 Hz, 1H), 7.57 (brdd, J = 8.1, 7.5 Hz, 2H), 7.52 (D, J = 7.7 Hz, 1H), 7.39 (m, 1H), 6.20 (d, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-177.0 (s, 1F).
Example-15

To a dimethyl sulfoxide solution (1.0 mL) of 2-iodopyridine (103 mg, 0.50 mmol), tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine at room temperature under an argon atmosphere. Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 100 ° C. for 12 hours. Water (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (1: 1)] to give 2- [fluoro (phenylsulfonyl) methyl] pyridine (31.4 mg, Yield 25%) was obtained as a brown crystal, and 2-fluoro-2-phenylsulfonyl-2-pyridyl acetate tert-butyl (119 mg, yield 68%) was obtained as a brown viscous body. 2-Fluoro-2-phenylsulfonyl-2-pyridyl acetate tert-butyl: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.63 (d, J = 4.6 Hz, 1H), 7.87-7.83 ( m, 3H), 7.79 (ddd, J = 7.7, 7.7, 1.4 Hz, 1H), 7.67 (brt, J = 7.5 Hz, 1H), 7.51 (brdd, J = 8.2, 7.5 Hz, 2H), 7.38 (m, 1H), 1.46 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-150.8 (s, 1F).
Example-16

To a dimethylsulfoxide solution (1.0 mL) of 1-benzyl-4-iodo-1H-pyrazole (122 mg, 0.43 mmol) was added tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg) at room temperature under an argon atmosphere. , 1.0 mmol), copper iodide (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol), potassium tert-butoxide (112 mg, 1.0 mmol), and And stirred for 12 hours. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 4 hr. 1 M hydrochloric acid (1.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1-benzyl-4- [fluoro (phenylsulfonyl) methyl] -1H. -Pyrazole (18.4 mg, 13% yield) was obtained as a yellow solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.86 (brd, J = 8.1 Hz, 2H), 7.68 (brt, J = 7.5 Hz, 1H), 7.56 (s, 1H), 7 .55-7.50 (m, 3H), 7.39-7.34 (m, 2H), 7.35 (s, 1H), 7.21 (brd, J = 7.6 Hz, 2H), 6 .03 (d, J = 46 Hz, 1H), 5.31 (d, J = 15.0 Hz, 1H), 5.27 (d, J = 15.0 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-166.4 (s, 1F).
Example-17

To a dimethyl sulfoxide solution (1.0 mL) of 1-isoquinoline (128 mg, 0.50 mmol), tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodide at room temperature under an argon atmosphere. Copper (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 100 ° C. for 12 hours. Water (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 1- [fluoro (phenylsulfonyl) methyl] isoquinoline (31.6 mg, Yield 21%) was obtained as a brown solid, and 2-fluoro-2- (1-isoquinolinyl) -2-phenylsulfonyl acetate tert-butyl (110 mg, yield 55%) was obtained as a yellow viscous body. 1- [Fluoro (phenylsulfonyl) methyl] isoquinoline: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.52 (d, J = 5.6 Hz, 1H), 8.44 (brd, J = 8.5 Hz, 1H) ), 7.91-7.88 (m, 3H), 7.76-7.65 (m, 4H), 7.54 (brdd, J = 8.2, 7.5 Hz, 2H), 6.80. (D, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-174.8 (s, 1F). 2-Fluoro-2- (1-isoquinolinyl) -2-phenylsulfonyl acetate tert-butyl: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.55 (d, J = 5.5 Hz, 1H), 8.46 ( Brd, J = 8.4 Hz, 1H), 8.06 (brd, J = 8.4 Hz, 2H), 7.85 (d, J = 8.2 Hz, 1H), 7.73-7.57 (m , 4H), 7.51 (brdd, J = 8.1, 7.5 Hz, 2H), 1.39 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-142.3 (s, 1F).
Example-18

To a dimethyl sulfoxide solution (1.0 mL) of 4-iodotoluene (109 mg, 0.50 mmol) at room temperature in an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 90 ° C. for 12 hours. 1M aqueous potassium hydroxide solution (1.0 mL) was added to the reaction mixture, and the mixture was stirred at 50 ° C. for 4 hr, 1 M hydrochloric acid (2.0 mL) was added, and the mixture was extracted with ethyl acetate (3.0 mL). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 4- [fluoro (phenylsulfonyl) methyl] toluene (73.9 mg, (Yield 56%) was obtained as a white yellow solid, and 2-fluoro-2-phenylsulfonyl-2- (4-tolyl) acetate (20.0 mg, yield 11%) was obtained as a yellow viscous body. 4- [fluoro (phenylsulfonyl) methyl] toluene: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81 (brd, J = 8.0 Hz, 2H), 7.69 (brt, J = 7.5 Hz, 1H) ), 7.54 (brdd, J = 8.0, 7.5 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H) 6.02 (d, J = 46 Hz, 1H), 2.38 (s, 3H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-174.6 (s, 1F). 2-Fluoro-2-phenylsulfonyl-2- (4-tolyl) acetate tert-butyl acetate: ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.71 (brd, J = 8.2 Hz, 2H), 7.64 ( brt, J = 7.5 Hz, 1H), 7.54 (brd, J = 8.4 Hz, 1H), 7.46 (brdd, J = 8.2, 7.5 Hz, 2H), 7.18 (brd , J = 8.4 Hz, 1H), 1.49 (s, 9H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-153.7 (s, 1F).
Example-19

To a dimethyl sulfoxide solution (1.0 mL) of 2-iodoanisole (119 mg, 0.50 mmol), tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine at room temperature under an argon atmosphere. Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 100 ° C. for 12 hours. A saturated aqueous ammonium chloride solution (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 2- [fluoro (phenylsulfonyl) methyl] anisole (23 mg, yield). 16%, purity 25%) was obtained as a yellow viscous body. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.87 (brd, J = 7.5 Hz, 1H), 7.84 (brd, J = 8.4 Hz, 2H), 7.70-7.40 (m, 5H), 6.94-6.90 (m, 1H), 6.63 (d, J = 46 Hz, 1H), 3.82 (s, 3H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-176.8 (s, 1F).
Example-20

To a dimethyl sulfoxide solution (1.0 mL) of 4-iodobiphenyl (144 mg, 0.50 mmol) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 100 ° C. for 12 hours. A saturated aqueous ammonium chloride solution (2.0 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (2.0 mL × 3). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The obtained crude product was purified by medium pressure column chromatography [silica gel (59 g), hexane-ethyl acetate (5: 2)] to give 4- [fluoro (phenylsulfonyl) methyl] biphenyl (73.4 mg, (45% yield) was obtained as a white yellow solid. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.02-7.97 (m, 2H), 7.85 (brd, J = 7.5 Hz, 2H), 7.70 (brd, 7.5 Hz, 2H) 7.62-7.52 (m, 5H), 7.48-7.36 (m, 3H), 6.11 (d, J = 46 Hz, 1H). ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-175.2 (s, 1F).
Example-21

To a dimethyl sulfoxide solution (1.0 mL) of 1-iodonaphthalene (127 mg, 0.50 mmol) at room temperature under an argon atmosphere, tert-butyl 2-fluoro-2-phenylsulfonylacetate (274 mg, 1.0 mmol), iodine Copper chloride (9.5 mg, 0.050 mmol), 2-picolinic acid (6.2 mg, 0.050 mmol) and potassium tert-butoxide (112 mg, 1.0 mmol) were added, and the mixture was stirred at 100 ° C. for 12 hours. The production of 1- [fluoro (phenylsulfonyl) methyl] naphthalene (production rate 51%) was confirmed by ¹⁹ F-NMR using p-difluorobenzene as an internal standard. ¹⁹ F-NMR (376 MHz, CDCl ₃ ) δ-173.3 (s, 1F).

Claims (7)

General formula (3a)

(In the formula, Ar ¹ represents a phenyl group which may be substituted with an alkyl group having 1 to 4 carbon atoms, Ar ³ represents an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, carbon An alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, a phenyl group substituted with an alkoxy group having 1 to 4 carbon atoms or a cyano group; an alkyl group having 1 to 6 carbon atoms, a carbon number A naphthyl group optionally substituted by a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group; An alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy having 1 to 4 carbon atoms A pyridyl group optionally substituted by a group or a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, A quinolinyl group optionally substituted by a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms , An aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or an isoquinolinyl group optionally substituted by a cyano group; or an alkyl group having 1 to 6 carbon atoms, or an alkyl group having 1 to 6 carbon atoms Haloalkyl group, alkenyl group having 2 to 7 carbon atoms, aryl group having 6 to 10 carbon atoms, aralkyl group having 7 to 11 carbon atoms, halogen atom, 1 to 4 carbon atoms Represents a pyrazolyl group optionally substituted with an alkoxy group or a cyano group.) Arylsulfonyl [(hetero) aryl] methyl fluoride represented by Ar ³ is an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy having 1 to 4 carbon atoms The arylsulfonyl [(hetero) aryl] methyl fluoride according to claim 1, which is a phenyl group substituted with a group or a cyano group. General formula (1)

(Wherein, R represents an alkyl group having 1 to 4 carbon atoms, and Ar ¹ represents a phenyl group which may be substituted with an alkyl group having 1 to 4 carbon atoms). A 2-fluoroacetic acid ester derivative is represented by the general formula (2) in the presence of a copper salt and a base.

(In the formula, Ar ² represents an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, or 1 carbon atom. A phenyl group optionally substituted by an alkoxy group having 1 to 4 carbon atoms or a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, or 6 to 10 carbon atoms An aryl group, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or a naphthyl group optionally substituted by a cyano group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, and 2 to carbon atoms An alkenyl group having 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or a pyridyl group optionally substituted with a cyano group; Substituted with an alkyl group, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms, or a cyano group A good quinolinyl group; an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, a halogen atom, an alkoxy having 1 to 4 carbon atoms An isoquinolinyl group optionally substituted by a group or a cyano group; or an alkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 7 carbon atoms, or an aryl group having 6 to 10 carbon atoms Represents an aralkyl group having 7 to 11 carbon atoms, a halogen atom, an alkoxy group having 1 to 4 carbon atoms or a pyrazolyl group optionally substituted with a cyano group. ) Represented by (wherein the reaction with hetero) aryl iodide derivative of the general formula (3)

(Wherein Ar ¹ and Ar ² represent the same meaning as described above). A method for producing arylsulfonyl [(hetero) aryl] methyl fluoride represented by: The method according to claim 3, wherein the general formula (1)

(Wherein R and Ar ¹ represent the same meaning as described above), a 2-arylsulfonyl-2-fluoroacetic acid ester derivative represented by the general formula (2) in the presence of a copper salt and a base.

(Wherein Ar ² represents the same meaning as described above) and is reacted with a (hetero) aryl iodide derivative represented by the general formula (3)

(Wherein Ar ¹ and Ar ² represent the same meaning as described above) and arylsulfonyl [(hetero) aryl] methyl fluoride represented by the general formula (4)

(Wherein R, Ar ¹ and Ar ² represent the same meaning as described above), a mixture of 2-arylsulfonyl-2-fluoro-2- (hetero) aryl acetate derivatives represented by By processing with the general formula (3)

(Wherein Ar ¹ and Ar ² represent the same meaning as described above). A production method for obtaining arylsulfonyl [(hetero) aryl] methyl fluoride represented by General formula (1) is the following formula (1a)

The method for producing arylsulfonyl [(hetero) aryl] methyl fluorides according to claim 3 or 4.   The method for producing arylsulfonyl [(hetero) aryl] methyl fluoride according to any one of claims 3 to 5, wherein the copper salt is copper (I) iodide. The method for producing arylsulfonyl [(hetero) aryl] methyl fluoride according to any one of claims 3 to 6, wherein the base is potassium t-butoxide.