JP2012201602A - Method for producing biphenyls - Google Patents

Abstract

（式中、Ｒ^１は、水素原子または炭素数１〜４のアルキル基を示す。）で表される２，２’−ビ（１，３，２−ベンゾジオキサボロール）誘導体とベンゼン誘導体Ａを反応させ、次いでアルカリ金属リン酸塩またアルカリ金属炭酸塩の存在下、ベンゼン誘導体Ｂを反応させ、一般式（４）

（式中、Ｒ^２およびＲ^３は、水素原子、ハロゲン原子等を示す。ｎおよびｍは１から４の整数を示す。）で表されるビフェニル類を製造する。
【選択図】なしThe present invention provides a simple method for producing biphenyls as raw materials for medical pesticides and functional materials.
In the presence of a palladium catalyst and an alkali metal carboxylate, the general formula (1)

(Wherein R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) and a benzene derivative represented by 2,2′-bi (1,3,2-benzodioxaborole) A is reacted, and then benzene derivative B is reacted in the presence of an alkali metal phosphate or alkali metal carbonate to give a compound of the general formula (4)

(Wherein R ² and R ³ represent a hydrogen atom, a halogen atom, etc., and n and m represent an integer of 1 to 4).
[Selection figure] None

Description

  The present invention relates to a method for producing biphenyls.

  Biphenyls are important compounds as synthetic intermediates for medical pesticides and electronic materials (for example, Non-Patent Document 1), and many production methods have been disclosed so far. Among them, the Suzuki-Miyaura cross coupling is a very useful method for producing biphenyls because the reagents used are stable and have low toxicity, and substrates having various functional groups can be used (non-patent literature). 1).

  In Suzuki-Miyaura cross-coupling, it is common to use boronated benzenes that have been pre-manufactured by a boronation reaction. However, in order to reduce the number of processes, a method of conducting boration and cross-coupling in one pot is also considered. Has been. Non-Patent Document 2 discloses 4,4,4 ′, 4 ′, 5,5,5 ′, 5′-octamethyl-2,2′-bi (1,3,2-dioxaborolane) in the presence of a palladium catalyst. Discloses a one-pot manufacturing method for biphenyls in which a benzene derivative is boronated and then another benzene derivative is reacted.

  On the other hand, 2,2′-bi (4,4 ′, 4 ′, 5,5,5 ′, 5′-octamethyl-2,2′-bi (1,3,2-dioxaborolane) is cheaper than There has been no report on a method of performing boration and cross coupling in one pot using a (1,3,2-benzodioxaborol) derivative.

Chem. Rev. 1995, 95, 2457 pages. J. et al. Org. Chem. 2003, 68, 3729.

  4,4,4 ', 4', 5,5,5 ', 5'-octamethyl-2,2'-bi (1,3,2-dioxaborolane) is very expensive. The present invention is to provide a simple method for producing biphenyls.

  As a result of intensive studies to solve the above problems, the present inventors have found that 2,2′-bi (1,3,2-benzodioxaborol) in the presence of a palladium catalyst and an alkali metal carboxylate. It was found that biphenyls can be produced by reacting a derivative with a benzene derivative and then reacting with another benzene derivative in the presence of an alkali metal phosphate or alkali metal carbonate.

  That is, the present invention provides a compound of the general formula (1) in the presence of a palladium catalyst and an alkali metal carboxylate.

（式中、Ｒ^１は、水素原子または炭素数１〜４のアルキル基を示す。）で表される２，２’−ビ（１，３，２−ベンゾジオキサボロール）誘導体と一般式（２）

(Wherein R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) and a general formula (2)

（式中、Ｒ^２は、水素原子；ハロゲン原子；ハロゲン原子、水酸基またはアミノ基で置換されていてもよい炭素数１〜６のアルキル基；ハロゲン原子で置換されていてもよい炭素数１〜４のアルコキシ基；炭素数１〜５のアシル基；（炭素数１〜４のアルコキシ）カルボニル基；水酸基；炭素数１〜４のアルキル基、フェニル基または炭素数２〜５のアシル基で置換されていてもよいアミノ基；（フッ素原子で置換されていてもよい炭素数１〜４のアルキル）チオ基；またはメルカプト基を示す。ｎは１から４の整数を示す。ｎが２から４の時、複数のＲ^２は同一又は相異なっていてもよい。またＲ^２がアルコキシ基であり、ｎが２以上であるとき、隣接するアルコキシ基は一体となって炭素数１から３のアルキレンジオキシ基を形成してもよい。Ｘ^１は、塩素原子、臭素原子、ヨウ素原子またはトリフルオロメチルスルホニルオキシ基を示す。）で表されるベンゼン誘導体Ａを反応させ、次い一般式（３）

(In the formula, R ² represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, n represents an integer of 1 to 4, where n is 2 to 4 A plurality of R ² may be the same or different, and when R ² is an alkoxy group and n is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ¹ is chlorine atom, a bromine atom, is reacted with benzene derivative A represented by.) Showing a iodine atom or a trifluoromethylsulfonyloxy group, the following have the general formula (3)

（式中、Ｒ^３は、水素原子；ハロゲン原子；ハロゲン原子、水酸基またはアミノ基で置換されていてもよい炭素数１〜６のアルキル基；ハロゲン原子で置換されていてもよい炭素数１〜４のアルコキシ基；炭素数１〜５のアシル基；（炭素数１〜４のアルコキシ）カルボニル基；水酸基；炭素数１〜４のアルキル基、フェニル基または炭素数２〜５のアシル基で置換されていてもよいアミノ基；（フッ素原子で置換されていてもよい炭素数１〜４のアルキル）チオ基；またはメルカプト基を示す。ｍは１から４の整数を示す。ｍが２から４の時、複数のＲ^３は同一又は相異なっていてもよい。またＲ^３がアルコキシ基であり、ｍが２以上であるとき、隣接するアルコキシ基は一体となって炭素数１から３のアルキレンジオキシ基を形成してもよい。Ｘ^２は、塩素原子、臭素原子、ヨウ素原子またはトリフルオロメチルスルホニルオキシ基を示す。）で表されるベンゼン誘導体Ｂを、アルカリ金属リン酸塩又はアルカリ金属炭酸塩の存在下に反応させることを特徴とする、一般式（４）

(In the formula, R ³ represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, m represents an integer of 1 to 4. m is an integer of 2 to 4. In this case, a plurality of R ³ may be the same or different, and when R ³ is an alkoxy group and m is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ² is a chlorine atom, a bromine atom, a benzene derivative B represented by showing a iodine atom or a trifluoromethylsulfonyloxy group.) Are reacted in the presence of an alkali metal phosphate or alkali metal carbonate The general formula (4)

（式中、Ｒ^２、Ｒ^３、ｎおよびｍは前記と同じ内容を示す。）で表されるビフェニル類の製造方法に関するものである。

(Wherein R ² , R ³ , n and m have the same contents as described above).

  Furthermore, the present invention provides a compound represented by the general formula (1) in the presence of a palladium catalyst and an alkali metal carboxylate.

（式中、Ｒ^１は、水素原子または炭素数１〜４のアルキル基を示す。）で表される２，２’−ビ（１，３，２−ベンゾジオキサボロール）誘導体と一般式（２）

(Wherein R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) and a general formula (2)

（式中、Ｒ^２は、水素原子；ハロゲン原子；ハロゲン原子、水酸基またはアミノ基で置換されていてもよい炭素数１〜６のアルキル基；ハロゲン原子で置換されていてもよい炭素数１〜４のアルコキシ基；炭素数１〜５のアシル基；（炭素数１〜４のアルコキシ）カルボニル基；水酸基；炭素数１〜４のアルキル基、フェニル基または炭素数２〜５のアシル基で置換されていてもよいアミノ基；（フッ素原子で置換されていてもよい炭素数１〜４のアルキル）チオ基；またはメルカプト基を示す。ｎは１から４の整数を示す。ｎが２から４の時、複数のＲ^２は同一又は相異なっていてもよい。またＲ^２がアルコキシ基であり、ｎが２以上であるとき、隣接するアルコキシ基は一体となって炭素数１から３のアルキレンジオキシ基を形成してもよい。Ｘ^１は、塩素原子、臭素原子、ヨウ素原子またはトリフルオロメチルスルホニルオキシ基を示す。）で表されるベンゼン誘導体Ａを反応させた後、一般式（５）

(In the formula, R ² represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, n represents an integer of 1 to 4, where n is 2 to 4 A plurality of R ² may be the same or different, and when R ² is an alkoxy group and n is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ¹ is chlorine atom, a bromine atom, after reacting the benzene derivative A represented by.) Showing a iodine atom or a trifluoromethylsulfonyloxy group, the general formula (5)

（式中、Ｒ^４およびＲ^５は各々独立に水素原子またはメチル基を示す。Ａはメチレン基、ジメチルメチレン基、エチレン基または単結合を示す。）で表されるジオール類を反応させ、次いで、一般式（３）

(Wherein R ⁴ and R ⁵ each independently represents a hydrogen atom or a methyl group, A represents a methylene group, a dimethylmethylene group, an ethylene group or a single bond), And general formula (3)

（式中、Ｒ^３は、水素原子；ハロゲン原子；ハロゲン原子、水酸基またはアミノ基で置換されていてもよい炭素数１〜６のアルキル基；ハロゲン原子で置換されていてもよい炭素数１〜４のアルコキシ基；炭素数１〜５のアシル基；（炭素数１〜４のアルコキシ）カルボニル基；水酸基；炭素数１〜４のアルキル基、フェニル基または炭素数２〜５のアシル基で置換されていてもよいアミノ基；（フッ素原子で置換されていてもよい炭素数１〜４のアルキル）チオ基；またはメルカプト基を示す。ｍは１から４の整数を示す。ｍが２から４の時、複数のＲ^３は同一又は相異なっていてもよい。またＲ^３がアルコキシ基であり、ｍが２以上であるとき、隣接するアルコキシ基は一体となって炭素数１から３のアルキレンジオキシ基を形成してもよい。Ｘ^２は、塩素原子、臭素原子、ヨウ素原子またはトリフルオロメチルスルホニルオキシ基を示す。）で表されるベンゼン誘導体Ｂを、アルカリ金属リン酸塩又はアルカリ金属炭酸塩の存在下に反応させることを特徴とする、一般式（４）

(In the formula, R ³ represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, m represents an integer of 1 to 4. m is an integer of 2 to 4. In this case, a plurality of R ³ may be the same or different, and when R ³ is an alkoxy group and m is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ² is a chlorine atom, a bromine atom, a benzene derivative B represented by showing a iodine atom or a trifluoromethylsulfonyloxy group.) Are reacted in the presence of an alkali metal phosphate or alkali metal carbonate The general formula (4)

（式中、Ｒ^２、Ｒ^３、ｎおよびｍは前記と同じ内容を示す。）で表されるビフェニル類の製造方法に関するものである。

(Wherein R ² , R ³ , n and m have the same contents as described above).

  The present invention is described in further detail below. First, the 2,2′-bi (1,3,2-benzodioxaborole) derivative (1), the benzene derivative A (2), and the benzene derivative B (3) will be described.

The alkyl group having 1 to 4 carbon atoms represented by R ¹ of the 2,2′-bi (1,3,2-benzodioxaborole) derivative (1) may be either linear or branched. Specifically, methyl group, ethyl group, propyl group, isopropyl group, butyl group, sec-butyl group, tert-butyl group and isobutyl group can be exemplified. As R ¹ , a hydrogen atom or a 2,2′-bi (1,3,2-benzodioxaborole) derivative (1) is easily available, and the yield of biphenyls (4) is good. A tert-butyl group is preferable, and a hydrogen atom is more preferable.

The benzene derivative A (2) of the present invention can be produced by a commercially available product or by a known method. Hereinafter, specific examples of the benzene derivative A (2) will be described in more detail. The alkyl group having 1 to 6 carbon atoms represented by R ² of the benzene derivative A (2) may be linear, branched or cyclic, and is methyl, ethyl, propyl, isopropyl, cyclopropyl Group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,2-dimethyl group Propyl group, 1-ethylpropyl group, cyclopentyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl Group, 2,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 3,3-dimethyl group Butyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methyl Propyl group, cyclohexyl group, cyclopropylmethyl group, 1-cyclopropylethyl group, 2-cyclopropylethyl group, 1-cyclopropylpropyl group, 2-cyclopropylpropyl group, 3-cyclopropylpropyl group, 2-cyclopropyl Examples thereof include a cyclobutylmethyl group, a 1-cyclobutylethyl group, a 2-cyclobutylethyl group, and a cyclopentylmethyl group. These alkyl groups may be substituted with a halogen atom, an amino group or a hydroxyl group, specifically, a trifluoromethyl group, a difluoromethyl group, a fluoromethyl group, a 2,2,2-trifluoroethyl group, 1,1,1,3,3,3-hexafluoroisopropyl group, trichloromethyl group, dichloromethyl group, chloromethyl group, 2,2,2-trichloroethyl group, 1,1,1,3,3,3 -Hexachloroisopropyl group, tribromomethyl group, dibromomethyl group, bromomethyl group, 2,2,2-tribromoethyl group, 1,1,1,3,3,3-hexabromoisopropyl group, 2-aminoethyl group 3-aminopropyl group, 4-aminobutyl group, 5-aminopentyl group, 6-aminohexyl group, 2-hydroxyethyl group, 3-hydroxypropylene Group, 4-hydroxybutyl group, 5-hydroxypentyl group, can be exemplified 6-hydroxyhexyl group.

The alkoxy group having 1 to 4 carbon atoms represented by R ² may be linear or branched, and is a methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, sec-butyloxy group, tert- A butyloxy group or an isobutyloxy group can be illustrated. These alkoxy groups may be substituted with a halogen atom, and are a trifluoromethoxy group, 2,2,2-trifluoroethoxy group, 1,1,1,3,3,3-hexafluoroisopropyloxy group, Trichloromethoxy group, dichloromethoxy group, chloromethoxy group, 2,2,2-trichloroethoxy group, 1,1,1,3,3,3-hexachloroisopropyloxy group, tribromomethoxy group, dibromomethoxy group, bromomethoxy Group, 2,2,2-tribromoethoxy group, 1,1,1,3,3,3-hexabromoisopropyl oxy group, perfluoropropyl group, perfluorobutyl group and the like.

The acyl group having 1 to 5 carbon atoms represented by R ² may be either linear or branched, and is an acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, sec-butylcarbonyl group. And a pivaloyl group.

The (carbonyl group having 1 to 4 carbon atoms) carbonyl group represented by R ² may be linear or branched, and is a methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, or butoxycarbonyl group. , Isobutoxycarbonyl group, sec-butoxycarbonyl group, tert-butoxycarbonyl group and the like.

Examples of the halogen atom represented by R ² include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

The amino group which may be substituted with an alkyl group having 1 to 4 carbon atoms, a phenyl group or an acyl group having 2 to 5 carbon atoms represented by R ² may be either linear or branched. Specifically, amino group, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, sec-butylamino group, tert-butylamino group, dimethylamino group, diethylamino group, dipropylamino Group, dibutylamino group, ethylmethylamino group, methylpropylamino group, butylmethylamino group, phenylamino group, diphenylamino group, methylphenylamino group, acetylamino group, propionylamino group, butyrylamino group, isobutyrylamino group , Valerylamino group, isovalerylaminol group, sec-butylcarbonylamino group, pivaloylamino group and the like.

The alkyl group of the thio group (alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) represented by R ² may be either linear or branched. More specifically, the (thioalkyl optionally substituted with fluorine atom) thio group represented by R ² is methylthio group, ethylthio group, propylthio group, isopropylthio group, butylthio group , Sec-butylthio group, tert-butylthio group, isobutylthio group, trifluoromethylthio group, 2,2,2-trifluoroethylthio group, 1,1,1,3,3,3-hexafluoroisopropylthio group, etc. Can be illustrated.

When R ² is an alkoxy group and n is 2 or more, adjacent alkoxy groups may be combined to form an alkylenedioxy group having 1 to 3 carbon atoms. More specifically, a methylenedioxy group, an ethylenedioxy group, a propylenedioxy group and the like can be exemplified.

X ¹ is preferably a bromine atom in that the yield of biphenyls (4) is good and the benzene derivative A is easily available.

The benzene derivative B (3) of the present invention can be obtained as a commercial product or can be produced according to a known method. Further specific examples will be described in more detail. The alkyl group having 1 to 6 carbon atoms represented by R ³ of the benzene derivative B (3) may be linear, branched or cyclic, and is methyl, ethyl, propyl, isopropyl, cyclopropyl Group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, cyclobutyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,2-dimethyl group Propyl group, 1-ethylpropyl group, cyclopentyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl Group, 2,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 3,3-dimethyl group Butyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methyl Propyl group, cyclohexyl group, cyclopropylmethyl group, 1-cyclopropylethyl group, 2-cyclopropylethyl group, 1-cyclopropylpropyl group, 2-cyclopropylpropyl group, 3-cyclopropylpropyl group, 2-cyclopropyl Examples include cyclobutylmethyl group, 1-cyclobutylethyl group, 2-cyclobutylethyl group, cyclopentylmethyl group and the like. These alkyl groups may be substituted with a halogen atom, an amino group or a hydroxyl group, specifically, a trifluoromethyl group, a difluoromethyl group, a fluoromethyl group, a 2,2,2-trifluoroethyl group, 1,1,1,3,3,3-hexafluoroisopropyl group, trichloromethyl group, dichloromethyl group, chloromethyl group, 2,2,2-trichloroethyl group, 1,1,1,3,3,3 -Hexachloroisopropyl group, tribromomethyl group, dibromomethyl group, bromomethyl group, 2,2,2-tribromoethyl group, 1,1,1,3,3,3-hexabromoisopropyl group, 2-aminoethyl group 3-aminopropyl group, 4-aminobutyl group, 5-aminopentyl group, 6-aminohexyl group, 2-hydroxyethyl group, 3-hydroxypropylene Group, 4-hydroxybutyl group, 5-hydroxypentyl group, can be exemplified 6-hydroxyhexyl group.

The alkoxy group having 1 to 4 carbon atoms represented by R ³ may be linear or branched, and is a methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, sec-butyloxy group, tert- A butyloxy group and an isobutyloxy group can be illustrated. These alkoxy groups may be substituted with a halogen atom, and are a trifluoromethoxy group, 2,2,2-trifluoroethoxy group, 1,1,1,3,3,3-hexafluoroisopropyloxy group, Trichloromethoxy group, dichloromethoxy group, chloromethoxy group, 2,2,2-trichloroethoxy group, 1,1,1,3,3,3-hexachloroisopropyloxy group, tribromomethoxy group, dibromomethoxy group, bromomethoxy Group, 2,2,2-tribromoethoxy group, 1,1,1,3,3,3-hexabromoisopropyloxy group, perfluoropropyloxy group, perfluorobutyloxy group and the like.

The acyl group having 1 to 5 carbon atoms represented by R ³ may be linear or branched, and is an acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, sec-butylcarbonyl group. And pivaloyl group.

The (C1-C4 alkoxy) carbonyl group represented by R ³ may be either linear or branched, and is a methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group. , Isobutoxycarbonyl group, sec-butoxycarbonyl group, and tert-butoxycarbonyl group.

Examples of the halogen atom represented by R ³ include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

The amino group which may be substituted with an alkyl group having 1 to 4 carbon atoms, a phenyl group or an acyl group having 2 to 5 carbon atoms represented by R ³ may be either linear or branched. More specifically, amino group, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, sec-butylamino group, tert-butylamino group, dimethylamino group, diethylamino group, dipropyl Amino group, dibutylamino group, ethylmethylamino group, methylpropylamino group, butylmethylamino group, phenylamino group, diphenylamino group, methylphenylamino group, acetylamino group, propionylamino group, butyrylamino group, isobutyrylamino Group, valerylamino group, isovalerylaminol group, sec-butylcarbonylamino group, pivaloylamino group and the like.

The alkyl group of the thio group (alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) represented by R ³ may be either linear or branched. Specific examples of the thio group represented by R ³ (the alkyl having 1 to 4 carbon atoms optionally substituted with a fluorine atom) thio group include a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, Examples include sec-butylthio group, tert-butylthio group, trifluoromethylthio group, 2,2,2-trifluoroethylthio group, 1,1,1,3,3,3-hexafluoroisopropylthio group.

When R ³ is an alkoxy group and n is 2 or more, adjacent alkoxy groups may be combined to form an alkylenedioxy group having 1 to 3 carbon atoms. More specifically, a methylenedioxy group, an ethylenedioxy group, a propylenedioxy group and the like can be exemplified.

X ² is preferably a bromine atom in terms of good yield of biphenyls (4) and easy availability of the benzene derivative B (3).

  Next, the manufacturing method of this invention is demonstrated. The production method of the present invention comprises 2,2′-bi (1,3,2-benzodioxaborole) derivative (1) and benzene derivative A (2) in the presence of a palladium catalyst and an alkali metal carboxylate. It consists of a step 1 of reacting and a step 2 of reacting the benzene derivative B (3).

  The reaction of step 1 can be carried out in a solvent. Solvents that can be used include ether solvents such as tetrahydrofuran, diethyl ether, cyclopentyl methyl ether, methyl-tert-butyl ether, 1,2-dimethoxyethane, N, N-dimethylformamide, N-methylformamide, N-methyl. Amido solvents such as pyrrolidone, 1,3-dimethyl-2-imidazolidone, sulfoxide solvents such as dimethyl sulfoxide, diethyl sulfoxide, methanol, ethanol, 1-propanol, 2-propanol, 1,2-ethanediol, isopropyl alcohol, Alcohol solvents such as butanol, sec-butyl alcohol, tert-butyl alcohol, cyclohexanol, 1-hexanol, trifluoroethanol, 1,2-ethanediol, acetonitrile And an organic solvent of a nitrile solvent such like, can be exemplified water. Furthermore, these mixed solvents can be illustrated. From the viewpoint of good yield, a sulfoxide solvent or an alcohol solvent is preferable, and dimethyl sulfoxide or ethanol is more preferable. There is no restriction | limiting in particular in the usage-amount of a solvent.

  It is essential to perform the reaction of Step 1 in the presence of a palladium catalyst. Palladium catalysts that can be used include dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium, dichlorobis (triphenylphosphine) palladium, tetrakis (triphenylphosphine) palladium, bis (diphenylphosphinomethane) palladium. Bis (diphenylphosphinoethane) palladium, bis (diphenylphosphinobutane) palladium, bis (diphenylphosphinopropane) palladium, bis (diphenylphosphinoferrocene) palladium, tris [tri (tert-butyl) phosphine] palladium, dichlorobis Examples include phosphine-coordinated palladium complexes such as [tri (tert-butyl) phosphine)] palladium and dibromobis [tri (tert-butyl) phosphine)] palladium. It can be.

  These phosphine coordinated palladium complexes, dichlorobis (acetonitrile) palladium, dichlorobis (benzonitrile) palladium, palladium chloride, dichloro (1,5-cyclooctadiene) palladium, palladium acetate, (π-allyl) chloropalladium, Palladium compounds such as bis (acetylacetonato) palladium and palladium bromide, triphenylphosphine, trimethylphosphine, triethylphosphine, tripropylphosphine, triisopropylphosphine, tributylphosphine, triisobutylphosphine, tri-tert-butylphosphine, tri Cyclohexylphosphine, 1,2-bis (2,5-diethylphosphorano) ethane, cyclohexyldiphenylphosphine, methyldiphenylphosphine Ethyldiphenylphosphine, propyldiphenylphosphine, isopropyldiphenylphosphine, butyldiphenylphosphine, isobutyldiphenylphosphine, tert-butyldiphenylphosphine, 9,9-dimethyl-4,5-bis (diphenylphosphino) xanthene, 2- (diphenylphosphino) ) -2 ′-(N, N-dimethylamino) biphenyl, 1,2-bis (2,5-dimethylphosphorano) benzene, 1,1′-bis (diisopropylphosphino) ferrocene, 1,2-bis ( 2,5-diisopropylphosphorano) benzene, 1,2-bis (2,5-diisopropylphosphorano) benzene, 2- (di-tert-butylphosphino) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 2- (Dicyclohex Silphosphino) -2′-methylbiphenyl, bis (diphenylphosphino) methane, 1,2-bis (diphenylphosphino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4-bis (diphenylphosphino) ) Butane, 1,4-bis (diphenylphosphino) pentane, 1,1′-bis (diphenylphosphino) ferrocene, cis-1,2-bis (diphenylphosphino) ethylene, bis (2-diphenylphosphinoethyl) ) Phenylphosphine, 1,2-bis (diphenylphosphino) propane, tris (3,5-dimethylphenyl) phosphine, tris (4-methoxyphenyl) phosphine, tris (2,4,6-trimethoxyphenyl) phosphine, Tri (m-tolyl) phosphine, tri (o-tolyl) phosphine Tri (p-tolyl) phosphine, 1,2-bis (diphenylphosphino) benzene, 2,2′-bis (diphenylphosphino) -1,1′-biphenyl, bis (2-methoxyphenyl) phenylphosphine, 1 , 2-bis (diphenylphosphino) benzene, 1- [2- (diphenylphosphino) ferrocenyl] ethyldi-tert-butylphosphine, 2-dicyclohexylphosphino-2 ′-(N, N-dimethylamino) biphenyl, tris (Trimethylsilyl) phosphine, 2-di-tert-butylphosphino-2 ′-(N, N-dimethylamino) biphenyl, 2-di-tert-butylphosphino-2′-methylbiphenyl, 2- (dicyclohexylphosphino ) Biphenyl and 2- (dicyclohexylphosphino) -2 ', ', It can be used a palladium catalyst which is a combination of a tertiary phosphine such as 6'-triisopropyl-1,1'-biphenyl. When using a palladium catalyst in which a phosphine coordination palladium complex or a palladium compound and a tertiary phosphine are combined, the molar ratio of palladium and tertiary phosphine is not particularly limited, but is preferably 0.1 to 100 in terms of good yield. 0.5 to 5 is more preferable.

  As a palladium catalyst, dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium, dichlorobis (triphenylphosphine) palladium, tetrakis (triphenylphosphine) palladium, Palladium catalyst combining dichlorobis (acetonitrile) palladium, palladium chloride or palladium acetate and triphenylphosphine is preferred. In particular, dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium is preferable.

  Although there is no restriction | limiting in the usage-amount of a palladium catalyst, The quantity of palladium catalyst suitably selected by the kind of reaction substrate and solvent, and reaction conditions can be used. From the viewpoint of good yield of biphenyls (4), it is preferable to use 0.0000001 mol% to 50 mol% of palladium catalyst with respect to benzene derivative A (2), and there is no excess or deficiency of reaction substrate or palladium catalyst. From the viewpoint that the reaction can be completed, it is more preferable to use 0.001 mol% to 10 mol% of palladium catalyst, particularly 0.01 to 5 mol%.

  It is essential to carry out the reaction in Step 1 in the presence of an alkali metal carboxylate. Examples of the alkali metal carboxylate that can be used include alkali metal acetates such as lithium acetate, sodium acetate, potassium acetate, and cesium acetate, propionate, butyrate, and the like, and a mixture thereof may be used. From the viewpoint of good yield, alkali metal acetate is preferable, and sodium acetate, potassium acetate or a mixture thereof is more preferable.

  Although there is no restriction | limiting in particular in the usage-amount of alkali metal carboxylate, It is preferable to use 1 equivalent or more with respect to benzene derivative A (2) at a point with a sufficient yield.

  Although there is no restriction | limiting in particular in the reaction temperature of the process 1, Reaction can be implemented at the temperature suitably selected from the temperature of 0-200 degreeC, and it was suitably selected from the temperature of 50-150 degreeC in the point with a sufficient yield. Preferably it is carried out at temperature. There is no particular limitation on the reaction time.

  There is no restriction | limiting in particular in the usage-amount of a 2,2'-bi (1,3,2- benzodioxaborole) derivative (1), and a yield is obtained by using 1 equivalent or more with respect to benzene derivative A (2). Biphenyls (4) can be obtained well.

  Step 1 may be performed with the addition of the diol (5). Diols (5) that can be used include 1,2-ethanediol, 1,3-propanediol, 2,3-butanediol, 2,3-dimethyl-2,3-butanediol, 1,2- Dihydroxybenzene, 2,2-dimethyl-1,3-propanediol, 2,4-pentanediol, 2-methyl-2,4-pentanediol, 2,4-dimethyl-2,4-pentanediol, 2,5 -Hexanediol, 2,5-dimethyl-2,5-hexanediol and the like can be exemplified. 2,3-dimethyl-2,3-butanediol or 1,2-ethanediol is preferred because of good yield and easy availability. There is no restriction | limiting in particular in the usage-amount of diol (5).

  The reaction of step 2 can be carried out in a solvent. Solvents that can be used include ether solvents such as tetrahydrofuran, diethyl ether, cyclopentyl methyl ether, methyl-tert-butyl ether, 1,2-dimethoxyethane, N, N-dimethylformamide, N-methylformamide, N-methyl. Amido solvents such as pyrrolidone, 1,3-dimethyl-2-imidazolidone, sulfoxide solvents such as dimethyl sulfoxide, diethyl sulfoxide, methanol, ethanol, 1-propanol, 2-propanol, 1,2-ethanediol, isopropyl alcohol, Alcohol solvents such as butanol, sec-butyl alcohol, tert-butyl alcohol, cyclohexanol, 1-hexanol, trifluoroethanol, 1,2-ethanediol, acetonitrile And an organic solvent of a nitrile solvent such like, can be exemplified water. Furthermore, these mixed solvents can be illustrated. From the viewpoint of good yield, a sulfoxide solvent or an alcohol solvent is preferable, and dimethyl sulfoxide or ethanol is more preferable. From the viewpoint of convenience, it is preferable to carry out the reaction of Step 2 using the solvent of Step 1 as it is. There is no restriction | limiting in particular in the usage-amount of a solvent.

  It is essential to perform the reaction in Step 2 in the presence of an alkali metal phosphate or an alkali metal carbonate. Examples of the alkali metal phosphate that can be used include alkali metal phosphates such as lithium phosphate, sodium phosphate, potassium phosphate, and cesium phosphate, and a mixture thereof may be used. These alkali metal phosphates may be hydrated salts. From the viewpoint of good yield, sodium phosphate, potassium phosphate or a mixture thereof is more preferable. Examples of the alkali metal carbonate that can be used include alkali metal carbonates such as sodium carbonate, potassium carbonate, and cesium carbonate, magnesium carbonate, and the like, and a mixture thereof may be used. From the viewpoint of good yield, potassium carbonate, sodium carbonate, or a mixture thereof is more preferable. Although there is no restriction | limiting in particular in the usage-amount of an alkali metal phosphate or carbonate, It is preferable to use 1 equivalent or more with respect to benzene derivative B (3) at a point with a sufficient yield.

  Although there is no restriction | limiting in particular in the reaction temperature of reaction of the process 2, It is preferable to carry out reaction at the temperature selected suitably from the temperature of 0-200 degreeC, and it is preferable to carry out at 50-150 degreeC at a point with a sufficient yield. . There is no particular limitation on the reaction time.

  There are no particular restrictions on the purification method of biphenyls (4), and general-purpose methods such as solvent extraction, column chromatography, preparative thin layer chromatography, preparative liquid chromatography, recrystallization, distillation or sublimation are required as necessary. By using these, the biphenyls (4) can be purified.

  INDUSTRIAL APPLICABILITY The present invention can easily obtain biphenyls useful for the synthesis of medicines, agricultural chemicals and electronic materials.

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

  Example-1

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸メチル（１．００ｍｍｏｌ，２１５ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に２，３−ジメチル−２，３−ブタンジオール（２．２０ｍｍｏｌ，２６０ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、と５−ブロモ−１，３−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、ヘキサン層に生成物を抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３’，５’−ジメチル−１，１’−ビフェニル−４−カルボン酸メチルを得た（２０９ｍｇ，収率８７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３９（６Ｈ，ｓ），δ３．９４（３Ｈ，ｓ），δ７．０４（１Ｈ，ｓ），δ７．２４（２Ｈ，ｓ），δ７．６４（２Ｈ，ｄｄ，Ｊ＝２．０ ａｎｄ ８．６Ｈｚ），δ８．５９（２Ｈ，ｄｄ，Ｊ＝２．０ ａｎｄ ８．６Ｈｚ）．
ＭＳ（ｍ／ｚ）：２４０［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and methyl 4-bromobenzoate (1.00 mmol, 215 mg) were added and stirred at 80 ° C. for 2 hours. 2,3-Dimethyl-2,3-butanediol (2.20 mmol, 260 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg) and 5-bromo-1,3-dimethylbenzene (1.00 mmol, 185 mg) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into the hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid methyl 3 ′, 5′-dimethyl-1,1′-biphenyl-4-carboxylate (209 mg, yield 87%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.39 (6H, s), δ 3.94 (3H, s), δ 7.04 (1H, s), δ 7.24 (2H, s), δ7 .64 (2H, dd, J = 2.0 and 8.6 Hz), δ 8.59 (2H, dd, J = 2.0 and 8.6 Hz).
MS (m / z): 240 [M] ^<+> .

Example-2
The same procedure was carried out except that the potassium phosphate trihydrate of Example-1 was changed to 2.00 mmol (532 mg), and methyl 3 ′, 5′-dimethyl-1,1′-biphenyl-4-carboxylate Was confirmed by ¹ H NMR (NMR yield 86%).

Example-3
The same procedure as in Example 1 was carried out except that 2,3-dimethyl-2,3-butanediol was not added, and methyl 3 ′, 5′-dimethyl-1,1′-biphenyl-4-carboxylate Was confirmed by ¹ H NMR (NMR yield 88%).

Example-4
The same operation was performed except that sodium carbonate (3.00 mmol, 317 mg) was used in place of the potassium phosphate trihydrate of Example-1, and 3 ', 5'-dimethyl-1,1'- Formation of methyl biphenyl-4-carboxylate was confirmed by ¹ H NMR (NMR yield 81%).

Example-5
The same operation was carried out except that potassium carbonate (3.00 mmol, 415 mg) was used in place of the potassium phosphate trihydrate of Example-1, and 3 ', 5'-dimethyl-1,1'- Formation of methyl biphenyl-4-carboxylate was confirmed by ¹ H NMR (NMR yield 86%).

Example-6
The same operation was performed except that cesium carbonate (3.00 mmol, 977 mg) was used in place of the potassium phosphate trihydrate of Example-1, and 3 ′, 5′-dimethyl-1,1′- Formation of methyl biphenyl-4-carboxylate was confirmed by ¹ H NMR (NMR yield 67%).

Example-7
The same procedure was carried out except that the potassium phosphate trihydrate of Example-4 was changed to 3.50 mmol (931 mg), and methyl 3 ′, 5′-dimethyl-1,1′-biphenyl-4-carboxylate Was confirmed by ¹ H NMR (NMR yield: 80%).

Example-8
In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.60 mmol, 353 mg), dimethyl sulfoxide (6.0 mL) and methyl 4-bromobenzoate (1.00 mmol, 215 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. 2,3-Dimethyl-2,3-butanediol (2.20 mmol, 260 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg) and 5-bromo-1,3-dimethylbenzene (1.00 mmol, 185 mg) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, the formation of methyl 3 ′, 5′-dimethyl-1,1′-biphenyl-4-carboxylate was confirmed by ¹ H NMR (NMR yield 98%).

Example-9
The same operation was carried out except that sodium carbonate (3.00 mmol, 317 mg) was used in place of the potassium phosphate trihydrate of Example-8, and 3 ′, 5′-dimethyl-1,1′- Formation of methyl biphenyl-4-carboxylate was confirmed by ¹ H NMR (NMR yield 71%).

Example-10
The same operation was performed except that potassium carbonate (3.00 mmol, 415 mg) was used in place of the potassium phosphate trihydrate of Example-8, and 3 ', 5'-dimethyl-1,1'- Formation of methyl biphenyl-4-carboxylate was confirmed by ¹ H NMR (NMR yield 78%).

Example-11
The same operation was performed except that cesium carbonate (3.00 mmol, 977 mg) was used instead of the potassium phosphate trihydrate of Example-8, and 3 ′, 5′-dimethyl-1,1′- The formation of methyl biphenyl-4-carboxylate was confirmed by ¹ H NMR (NMR yield 91%).

Example-12
The same procedure was carried out except that the potassium phosphate trihydrate of Example-8 was changed to 3.50 mmol (931 mg), and methyl 3 ′, 5′-dimethyl-1,1′-biphenyl-4-carboxylate Was confirmed by ¹ H NMR (NMR yield 99%).

  Example-13

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。次いで１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加えて、８０℃で３０分攪拌した。得られた反応溶液にリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモベンジルアルコール（１．００ ｍｍｏｌ， １８７ ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−ヒドロキシメチル−１，１’−ビフェニル−４−カルボン酸エチルを得た（１７２ｍｇ，収率６７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４０（３Ｈ，ｔ，Ｊ＝７．３Ｈｚ），δ４．３９（２Ｈ，ｑ，Ｊ＝６．９Ｈｚ），δ４．７４（２Ｈ，ｑ，Ｊ＝４．６Ｈｚ），δ７．４５（２Ｈ，ｄ，Ｊ＝８．２Ｈｚ），δ７．６１（２Ｈ，ｄ，Ｊ＝８．２Ｈｚ），７．６４（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ８．１０（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. Subsequently, 1,2-ethanediol (2.20 mmol, 137 mg) was added and stirred at 80 ° C. for 30 minutes. To the obtained reaction solution, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromobenzyl alcohol (1.00 mmol, 187 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. Stir for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 4′-hydroxymethyl-1,1′-biphenyl-4-carboxylate (172 mg, yield 67%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.40 (3H, t, J = 7.3 Hz), δ 4.39 (2H, q, J = 6.9 Hz), δ 4.74 (2H, q , J = 4.6 Hz), δ 7.45 (2H, d, J = 8.2 Hz), δ 7.61 (2H, d, J = 8.2 Hz), 7.64 (2H, d, J = 8. 6 Hz), δ 8.10 (2H, d, J = 8.6 Hz).

  Example-14

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモベンゾトリフルオリド（１．００ｍｍｏｌ，２２５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−トリフルオロメチル−１，１’−ビフェニル−４−カルボン酸エチルを得た（２１５ｍｇ，収率７３％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４２（３Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ４．４１（２Ｈ，ｑ，Ｊ＝７．１Ｈｚ），δ７．６６（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．６２（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．７２（４Ｈ，ｓ），δ８．１４（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ）．
ＭＳ（ｍ／ｚ）：２９５［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromobenzotrifluoride (1.00 mmol, 225 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 4′-trifluoromethyl-1,1′-biphenyl-4-carboxylate (215 mg, yield 73%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.42 (3H, t, J = 7.1 Hz), δ 4.41 (2H, q, J = 7.1 Hz), δ 7.66 (2H, d , J = 8.6 Hz), δ 7.62 (2H, d, J = 8.7 Hz), δ 7.72 (4H, s), δ 8.14 (2H, d, J = 8.7 Hz).
MS (m / z): 295 [M] ^<+> .

  Example-15

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−４−（トリフルオロメトキシ）ベンゼン（１．００ｍｍｏｌ，２４１ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−トリフルオロメトキシ−１，１’−ビフェニル−４−カルボン酸エチルを得た（２７９ｍｇ，収率９０％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４２（３Ｈ，ｔ，Ｊ＝７．２Ｈｚ），δ４．４１（２Ｈ，ｑ，Ｊ＝７．２Ｈｚ），δ７．３１（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．６２（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．６４（２Ｈ，ｄ，Ｊ＝８．９Ｈｚ），δ８．１２（２Ｈ，ｄ，Ｊ＝８．９Ｈｚ）．
ＭＳ（ｍ／ｚ）：３１０［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-4- (trifluoromethoxy) benzene (1.00 mmol, 241 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. Stir for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 4′-trifluoromethoxy-1,1′-biphenyl-4-carboxylate (279 mg, yield 90%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): ¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.42 (3H, t, J = 7.2 Hz), δ 4.41 (2H, q, J = 7.2 Hz), δ 7.31 (2H, d, J = 8.6 Hz), δ 7.62 (2H, d, J = 8.6 Hz), δ 7.64 (2H, d, J = 8.9 Hz) , Δ 8.12 (2H, d, J = 8.9 Hz).
MS (m / z): 310 [M] ^&lt; ^{+ &gt};.

  Example-16

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−４−クロロベンゼン（１．００ｍｍｏｌ， １９１ ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−クロロ−１，１’−ビフェニル−４−カルボン酸エチルを得た（２４０ｍｇ，収率９２％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ４．３９（２Ｈ，ｑ，Ｊ＝７．１Ｈｚ），δ７．４３（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．５５（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．６２（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ８．１１（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-4-chlorobenzene (1.00 mmol, 191 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. . After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 4′-chloro-1,1′-biphenyl-4-carboxylate (240 mg, yield 92%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.41 (3H, t, J = 7.1 Hz), δ 4.39 (2H, q, J = 7.1 Hz), δ 7.43 (2H, d , J = 8.7 Hz), δ 7.55 (2H, d, J = 8.7 Hz), δ 7.62 (2H, d, J = 8.7 Hz), δ 8.11 (2H, d, J = 8. 7 Hz).

  Example-17

反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモ−２−フルオロアニリン（１．００ｍｍｏｌ，１９０ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−アミノ−３’−フルオロ−１，１’−ビフェニル−４−カルボン酸エチルを得た（１０６ｍｇ，収率４１％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．２Ｈｚ），δ３．８５（２Ｈ，ｓ），δ４．３９（２Ｈ，ｑ，Ｊ＝７．２Ｈｚ），δ６．８４（１Ｈ，ｔ，Ｊ＝８．２Ｈｚ），δ７．２３−７．２５（３Ｈ，ｍ），δ７．５７（２Ｈ，ｄ，Ｊ＝８．８Ｈｚ），δ８．０６（２Ｈ，ｄ，Ｊ＝８．８Ｈｚ）。

In a reaction vessel, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0. 030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromo-2-fluoroaniline (1.00 mmol, 190 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. . After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 4′-amino-3′-fluoro-1,1′-biphenyl-4-carboxylate (106 mg, yield 41%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.41 (3H, t, J = 7.2 Hz), δ 3.85 (2H, s), δ 4.39 (2H, q, J = 7.2 Hz) ), Δ 6.84 (1H, t, J = 8.2 Hz), δ 7.23-7.25 (3H, m), δ 7.57 (2H, d, J = 8.8 Hz), δ 8.06 (2H) , D, J = 8.8 Hz).

  Example-18

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモチオフェノール（１．００ｍｍｏｌ，１８９ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−メルカプト−１，１’−ビフェニル−４−カルボン酸エチルを得た（８３ｍｇ，収率３２％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４０−１．４１（３Ｈ，ｍ），δ３．５８（１Ｈ，ｓ），δ４．３５−４．３９（２Ｈ，ｍ），δ７．２４（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ），δ７．４２（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．６３−７．６５（２Ｈ，ｍ），δ７．８７−７．９０（２Ｈ，ｍ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothiophenol (1.00 mmol, 189 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain ethyl 4′-mercapto-1,1′-biphenyl-4-carboxylate as a colorless transparent liquid (83 mg, yield 32%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ1.40 to 1.41 (3H, m), δ3.58 (1H, s), δ4.35 to 4.39 (2H, m), δ7. 24 (2H, d, J = 8.4 Hz), δ 7.42 (2H, d, J = 8.7 Hz), δ 7.63-7.65 (2H, m), δ 7.87-7.90 (2H , M).

  Example-19

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモチオアニソール（１．００ｍｍｏｌ，２０３ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−メチルチオ−１，１’−ビフェニル−４−カルボン酸エチルを得た（１９９ｍｇ，収率７３％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ２．５３（３Ｈ，ｓ），δ４．３９（２Ｈ，ｑ，Ｊ＝７．１Ｈｚ），δ７．３４（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．５６（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．６３（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ８．１０（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, potassium phosphate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain ethyl 4′-methylthio-1,1′-biphenyl-4-carboxylate as a colorless transparent liquid (199 mg, yield 73%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ1.41 (3H, t, J = 7.1 Hz), δ2.53 (3H, s), δ4.39 (2H, q, J = 7.1 Hz) ), Δ 7.34 (2H, d, J = 8.6 Hz), δ 7.56 (2H, d, J = 8.7 Hz), δ 7.63 (2H, d, J = 8.7 Hz), δ 8.10. (2H, d, J = 8.7 Hz).

  Example-20

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、２−ブロモアニソール（１．００ｍｍｏｌ，１８７ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の２’−メトキシ−１，１’−ビフェニル−４−カルボン酸エチルを得た（１９２ｍｇ，収率７５％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．０Ｈｚ），δ３．８１（３Ｈ，ｓ），δ４．３９（２Ｈ，ｑ，Ｊ＝７．０Ｈｚ），δ６．９９（１Ｈ，ｄ，Ｊ＝８．２Ｈｚ），δ７．０４（１Ｈ，ｔ，Ｊ＝７．６Ｈｚ），δ７．３１−３．３７（２Ｈ，ｍ），δ７．６０（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ８．１１（２Ｈ，ｄ，Ｊ＝８．６ Ｈｚ）．
ＭＳ（ｍ／ｚ）：２５６［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, potassium phosphate trihydrate (3.00 mmol, 798 mg), 2-bromoanisole (1.00 mmol, 187 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 2′-methoxy-1,1′-biphenyl-4-carboxylate (192 mg, yield 75%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ1.41 (3H, t, J = 7.0 Hz), δ3.81 (3H, s), δ4.39 (2H, q, J = 7.0 Hz) ), Δ 6.99 (1H, d, J = 8.2 Hz), δ 7.04 (1H, t, J = 7.6 Hz), δ 7.31-3.37 (2H, m), δ 7.60 (2H) , D, J = 8.6 Hz), δ 8.11 (2H, d, J = 8.6 Hz).
MS (m / z): 256 [M] ^<+> .

  Example-21

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−２−クロロベンゼン（１．００ｍｍｏｌ，１９１ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の２’−クロロ−１，１’−ビフェニル−４−カルボン酸エチルを得た（２３５ｍｇ，収率９０％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝６．９Ｈｚ），δ４．４１（２Ｈ，ｑ，Ｊ＝６．９Ｈｚ），δ７．３０−７．３４（３Ｈ，ｍ），δ７．４７−７．５２（３Ｈ，ｍ），δ８．１１（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate (3.00 mmol, 798 mg), 1-bromo-2-chlorobenzene (1.00 mmol, 191 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 2′-chloro-1,1′-biphenyl-4-carboxylate (235 mg, yield 90%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.41 (3H, t, J = 6.9 Hz), δ 4.41 (2H, q, J = 6.9 Hz), δ 7.30-7.34 (3H, m), δ 7.47-7.52 (3H, m), δ 8.11 (2H, d, J = 8.7 Hz).

  Example-22

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、２−ブロモベンゾトリフルオリド（１．００ｍｍｏｌ，２２５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の２’−トリフルオロメチル−１，１’−ビフェニル−４−カルボン酸エチルを得た（２４１ｍｇ，収率８２％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．２Ｈｚ），δ４．４１（２Ｈ，ｑ，Ｊ＝７．２Ｈｚ），δ７．３１（１Ｈ，ｄ，Ｊ＝７．４Ｈｚ），δ７．４０（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ），δ７．４９（１Ｈ，ｔ，Ｊ＝７．４Ｈｚ），δ７．５８（１Ｈ，ｔ，Ｊ＝７．４Ｈｚ），δ７．７６（１Ｈ，ｄ，Ｊ＝７．４Ｈｚ），δ８．０８（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ）．
ＭＳ（ｍ／ｚ）：２９４［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 2-bromobenzotrifluoride (1.00 mmol, 225 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 2′-trifluoromethyl-1,1′-biphenyl-4-carboxylate (241 mg, yield 82%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.41 (3H, t, J = 7.2 Hz), δ 4.41 (2H, q, J = 7.2 Hz), δ 7.31 (1H, d , J = 7.4 Hz), δ 7.40 (2H, d, J = 8.5 Hz), δ 7.49 (1H, t, J = 7.4 Hz), δ 7.58 (1H, t, J = 7. 4 Hz), δ 7.76 (1H, d, J = 7.4 Hz), δ 8.08 (2H, d, J = 8.5 Hz).
MS (m / z): 294 [M] ^<+> .

  Example-23

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３’，５’−ジメチル−１，１’−ビフェニル−４−カルボン酸エチルを得た（２２１ｍｇ，収率８７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．０Ｈｚ），δ２．３９（６Ｈ，ｓ），δ４．４０（２Ｈ，ｑ，Ｊ＝７．０Ｈｚ），δ７．０３（１Ｈ，ｓ），δ７．２３（２Ｈ，ｓ），δ７．６３（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ），δ８．０８（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 3 ′, 5′-dimethyl-1,1′-biphenyl-4-carboxylate (221 mg, yield 87%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.41 (3H, t, J = 7.0 Hz), δ 2.39 (6H, s), δ 4.40 (2H, q, J = 7.0 Hz) ), Δ 7.03 (1H, s), δ 7.23 (2H, s), δ 7.63 (2H, d, J = 8.5 Hz), δ 8.08 (2H, d, J = 8.5 Hz).

  Example-24

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，４，５−トリフルオロベンゼン（１．００ｍｍｏｌ，２１１ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３’，４’，５’−トリフルオロ−１，１’−ビフェニル−４−カルボン酸エチルを得た（２４４ｍｇ，収率８７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４２（３Ｈ，ｔ，Ｊ＝７．５Ｈｚ），δ４．４１（２Ｈ，ｑ，Ｊ＝７．４Ｈｚ），δ７．２３（２Ｈ，ｔ，Ｊ＝６．５Ｈｚ），δ７．５６（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ），δ８．１２（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) and dimethyl sulfoxide (2.0 mL) were added, and further 80 ° C. For 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain ethyl 3 ′, 4 ′, 5′-trifluoro-1,1′-biphenyl-4-carboxylate as a colorless transparent liquid (244 mg, yield 87%). ).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.42 (3H, t, J = 7.5 Hz), δ 4.41 (2H, q, J = 7.4 Hz), δ 7.23 (2H, t , J = 6.5 Hz), δ 7.56 (2H, d, J = 8.5 Hz), δ 8.12 (2H, d, J = 8.5 Hz).

  Example-25

反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、３，５−ビス（トリフルオロメチル）ブロモベンゼン（１．００ｍｍｏｌ，２９３ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３’，５’−ビス（トリフルオロメチル）−１，１’−ビフェニル−４−カルボン酸エチルを得た（３３７ｍｇ，収率９３％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ４．４０（２Ｈ，ｑ，Ｊ＝７．１Ｈｚ），δ７．６８（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．９０（１Ｈ，ｓ），δ８．０４（２Ｈ，ｓ），δ８．１８（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ）．
ＭＳ（ｍ／ｚ）：３６２［Ｍ］^＋。

In a reaction vessel, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0. 030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 3,5-bis (trifluoromethyl) bromobenzene (1.00 mmol, 293 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. Stir for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 3 ′, 5′-bis (trifluoromethyl) -1,1′-biphenyl-4-carboxylate (337 mg, yield 93). %).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.41 (3H, t, J = 7.1 Hz), δ 4.40 (2H, q, J = 7.1 Hz), δ 7.68 (2H, d , J = 8.7 Hz), δ 7.90 (1H, s), δ 8.04 (2H, s), δ 8.18 (2H, d, J = 8.7 Hz).
MS (m / z): 362 [M] ^<+> .

  Example-26

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および２−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−４−クロロベンゼン（１．００ｍｍｏｌ，１９１ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−クロロ−１，１’−ビフェニル−２−カルボン酸エチルを得た（２０１ｍｇ，収率７７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．０６（３Ｈ，ｔ，Ｊ＝７．２Ｈｚ），δ４．１１（２Ｈ，ｑ，Ｊ＝７．２Ｈｚ），δ７．２３（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．３２（１Ｈ，ｄ，Ｊ＝７．６Ｈｚ），δ７．３６（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．４０−７．４６（１Ｈ，ｍ），δ７．５０−７．５４（１Ｈ，ｍ），δ７．８５（１Ｈ，ｄ，Ｊ＝７．７Ｈｚ）．
ＭＳ（ｍ／ｚ）：２６０［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 2-bromobenzoate (1.00 mmol, 229 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-4-chlorobenzene (1.00 mmol, 191 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 4′-chloro-1,1′-biphenyl-2-carboxylate (201 mg, yield 77%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.06 (3H, t, J = 7.2 Hz), δ 4.11 (2H, q, J = 7.2 Hz), δ 7.23 (2H, d , J = 8.7 Hz), δ 7.32 (1H, d, J = 7.6 Hz), δ 7.36 (2H, d, J = 8.7 Hz), δ 7.40-7.46 (1 H, m). , Δ 7.50-7.54 (1H, m), δ 7.85 (1 H, d, J = 7.7 Hz).
MS (m / z): 260 [M] ^<+> .

  Example-27

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および２−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、２’−ブロモアセトフェノン（１．００ｍｍｏｌ，１９９ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の２’−アセチル−１，１’−ビフェニル−２−カルボン酸エチルを得た（１９３ｍｇ，収率７２％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．０２（３Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ２．６１（３Ｈ，ｓ），δ４．０７（２Ｈ，ｑ，Ｊ＝７．１Ｈｚ），δ７．２１（１Ｈ，ｄ，Ｊ＝７．１Ｈｚ），δ７．２９（１Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ７．３７（１Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ７．４５（３Ｈ，ｍ），δ７．６２（１Ｈ，ｄ，Ｊ＝８．０Ｈｚ），δ７．９８（１Ｈ，ｔ，Ｊ＝８．０Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 2-bromobenzoate (1.00 mmol, 229 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, potassium phosphate trihydrate (3.00 mmol, 798 mg), 2′-bromoacetophenone (1.00 mmol, 199 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 2′-acetyl-1,1′-biphenyl-2-carboxylate (193 mg, yield 72%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.02 (3H, t, J = 7.1 Hz), δ 2.61 (3H, s), δ 4.07 (2H, q, J = 7.1 Hz) ), Δ 7.21 (1H, d, J = 7.1 Hz), δ 7.29 (1H, t, J = 7.1 Hz), δ 7.37 (1H, t, J = 7.1 Hz), δ 7.45. (3H, m), δ 7.62 (1H, d, J = 8.0 Hz), δ 7.98 (1H, t, J = 8.0 Hz).

  Example-28

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−３，４，５−トリフルオロベンゼン（１．００ｍｍｏｌ，２１１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加て、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−４−クロロベンゼン（１．００ｍｍｏｌ，１９１ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、、無色透明液体の４−クロロ−３’，４’，５’−トリフルオロ−１，１’−ビフェニルを得た（２０９ｍｇ，収率８６％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ７．１５（２Ｈ，ｄｄ，Ｊ＝８．４Ｈｚ），δ７．４２（４Ｈ，ｓ）．
ＭＳ（ｍ／ｚ）：２４２［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborol) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) were added, and the mixture was added at 80 ° C. For 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-4-chlorobenzene (1.00 mmol, 191 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain colorless and transparent liquid 4-chloro-3 ′, 4 ′, 5′-trifluoro-1,1′-biphenyl (209 mg, yield 86%). .
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 7.15 (2H, dd, J = 8.4 Hz), δ 7.42 (4H, s).
MS (m / z): 242 [M] ^<+> .

  Example-29

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−３，４，５−トリフルオロベンゼン（１．００ｍｍｏｌ，２１１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、２−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、、無色透明液体の３’，４’，５’−トリフルオロ−１，１’−ビフェニル−２−カルボン酸エチルを得た（１８５ｍｇ，収率６６％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．１５（３Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ４．１８（２Ｈ，ｑ，Ｊ＝７．１Ｈｚ），δ６．９２（２Ｈ，ｄｄ，Ｊ＝８．３Ｈｚ），δ７．２９（１Ｈ，ｄ，Ｊ＝７．５Ｈｚ），δ７．４６（１Ｈ，ｔ，Ｊ＝７．７Ｈｚ），δ７．５４（１Ｈ，ｔ，Ｊ＝７．７Ｈｚ），δ７．８９（１Ｈ，ｄ，Ｊ＝７．７Ｈｚ）．
ＭＳ（ｍ／ｚ）：２８１［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborol) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) were added, and the mixture was added at 80 ° C. For 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, potassium phosphate trihydrate (3.00 mmol, 798 mg), ethyl 2-bromobenzoate (1.00 mmol, 229 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 3 ′, 4 ′, 5′-trifluoro-1,1′-biphenyl-2-carboxylate (185 mg, yield 66). %).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 1.15 (3H, t, J = 7.1 Hz), δ 4.18 (2H, q, J = 7.1 Hz), δ 6.92 (2H, dd , J = 8.3 Hz), δ 7.29 (1H, d, J = 7.5 Hz), δ 7.46 (1H, t, J = 7.7 Hz), δ 7.54 (1H, t, J = 7. 7 Hz), δ 7.89 (1H, d, J = 7.7 Hz).
MS (m / z): 281 [M] ^<+> .

  Example-30

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−３，４，５−トリフルオロベンゼン（１．００ｍｍｏｌ，２１１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。得られた反応溶液にリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（０．５ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、ヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、、無色透明液体の３，４，５−トリフルオロ−３’，５’−ジメチル−１，１’−ビフェニルを得た（２０６ｍｇ，収率８７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３７（６Ｈ，ｓ），δ７．０２（１Ｈ，ｓ），δ７．０９（２Ｈ，ｓ），δ７．１６（２Ｈ，ｄｄ，Ｊ＝９．０Ｈｚ）．
ＭＳ（ｍ／ｚ）：２３６［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborol) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) were added, and the mixture was added at 80 ° C. For 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. To the obtained reaction solution, potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (0.5 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and Stir at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture and extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 3,4,5-trifluoro-3 ′, 5′-dimethyl-1,1′-biphenyl as a colorless transparent liquid (206 mg, yield 87%). ).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.37 (6H, s), δ 7.02 (1H, s), δ 7.09 (2H, s), δ 7.16 (2H, dd, J = 9.0 Hz).
MS (m / z): 236 [M] ^<+> .

  Example-31

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモベンゾトリフルオリド（１．００ｍｍｏｌ，２２５ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサンに抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−トリフルオロメチル−３，５−ジメチル−１，１’−ビフェニルを得た（２１８ｍｇ，収率８７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３９（６Ｈ，ｓ），δ７．０４（１Ｈ，ｓ），δ７．２０（２Ｈ，ｓ），δ７．６６（４Ｈ，ｓ）．
ＭＳ（ｍ／ｚ）：２５０［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 4-bromobenzotrifluoride (1.00 mmol, 225 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into hexane. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 4′-trifluoromethyl-3,5-dimethyl-1,1′-biphenyl (218 mg, yield 87%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.39 (6H, s), δ 7.04 (1H, s), δ 7.20 (2H, s), δ 7.66 (4H, s).
MS (m / z): 250 [M] ^<+> .

  Example-32

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−４−トリフルオロメトキシベンゼン（１．００ｍｍｏｌ，２４１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）、ジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、、無色透明液体の４’−トリフルオロメトキシ−３，５−ジメチル−１，１’−ビフェニルを得た（２０２ｍｇ，収率７６％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３６（６Ｈ，ｓ），δ７．００（１Ｈ，ｓ），δ７．１６（２Ｈ，ｓ），δ７．２５（２Ｈ，ｄ，Ｊ＝７．５Ｈｚ），δ７．５６（２Ｈ，ｄ，Ｊ＝７．５Ｈｚ）．
ＭＳ（ｍ／ｚ）：２６６［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4-trifluoromethoxybenzene (1.00 mmol, 241 mg) were added at 80 ° C. for 2 hours. Stir. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 4′-trifluoromethoxy-3,5-dimethyl-1,1′-biphenyl (202 mg, yield 76%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.36 (6H, s), δ 7.00 (1H, s), δ 7.16 (2H, s), δ 7.25 (2H, d, J = 7.5 Hz), δ 7.56 (2H, d, J = 7.5 Hz).
MS (m / z): 266 [M] ^<+> .

  Example-33

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ−２−フルオロアニリン（１．００ｍｍｏｌ，１９０ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３−フルオロ−３’，５’−ジメチル−１，１’−ビフェニル−４−アミンを得た（９０ｍｇ，収率４２％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３５（６Ｈ，ｓ），δ３．７３（２Ｈ，ｓ），δ６．８０（１Ｈ，ｄｄ，Ｊ＝８．４Ｈｚ），δ６．９３（１Ｈ，ｓ），δ７．１２（２Ｈ，ｓ），δ７．１７（１Ｈ，ｄｄ，Ｊ＝８．４Ｈｚ），δ７．２１−７．２４（１Ｈ，ｍ）．
ＭＳ（ｍ／ｚ）：２１５［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 4-bromo-2-fluoroaniline (1.00 mmol, 190 mg) were added and stirred at 80 ° C. for 2 hours. . 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 3-fluoro-3 ′, 5′-dimethyl-1,1′-biphenyl-4-amine (90 mg, yield 42%) as a colorless transparent liquid.
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.35 (6H, s), δ 3.73 (2H, s), δ 6.80 (1 H, dd, J = 8.4 Hz), δ 6.93 ( 1H, s), δ 7.12 (2H, s), δ 7.17 (1H, dd, J = 8.4 Hz), δ 7.21-7.24 (1 H, m).
MS (m / z): 215 [M] ^<+> .

  Example-34

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４’−ブロモアセトアニリド（１．００ｍｍｏｌ，２１５ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサンに抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体のＮ−アセチル−３’，５’−ジメチル−１，１’−ビフェニル−４−アミンを得た（９８ｍｇ，収率４１％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．１８（３Ｈ，ｓ），δ２．３６（６Ｈ，ｓ），δ６．９６（１Ｈ，ｓ），δ７．１７（２Ｈ，ｓ），δ７．５４（４Ｈ，ｄ，Ｊ＝３．４Ｈｚ）．
ＭＳ（ｍ／ｚ）：２３９［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 4′-bromoacetanilide (1.00 mmol, 215 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into hexane. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid N-acetyl-3 ′, 5′-dimethyl-1,1′-biphenyl-4-amine (98 mg, yield 41%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.18 (3H, s), δ 2.36 (6H, s), δ 6.96 (1H, s), δ 7.17 (2H, s), δ 7 .54 (4H, d, J = 3.4 Hz).
MS (m / z): 239 [M] ^<+> .

  Example-35

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモチオアニソール（１．００ｍｍｏｌ，２０３ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層にで抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３’，５’−ジメチル−４−メチルチオ−１，１’−ビフェニルを得た（６２ｍｇ，収率２７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３７（６Ｈ，ｓ），δ２．５１（３Ｈ，ｓ），δ６．９７（１Ｈ，ｓ），δ７．１８（２Ｈ，ｓ），δ７．３０（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ），δ７．５０（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ）．
ＭＳ（ｍ／ｚ）：２２８［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 4-bromothioanisole (1.00 mmol, 203 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into the hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 3 ′, 5′-dimethyl-4-methylthio-1,1′-biphenyl (62 mg, yield 27%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.37 (6H, s), δ 2.51 (3H, s), δ 6.97 (1H, s), δ 7.18 (2H, s), δ 7 .30 (2H, d, J = 8.5 Hz), δ 7.50 (2H, d, J = 8.5 Hz).
MS (m / z): 228 [M] ^<+> .

  Example-36

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモフェノール（１．００ｍｍｏｌ，１７３ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３’，５’−ジメチル−１，１’−ビフェニル−４−オールを得た（７５ｍｇ，収率３８％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３４（６Ｈ，ｓ），δ５．２４（１Ｈ，ｓ），δ６．８６（２Ｈ，ｄ，Ｊ＝８．８Ｈｚ），δ６．９４（１Ｈ，ｓ），δ７．１４（２Ｈ，ｓ），δ７．４４（２Ｈ，ｄ，Ｊ＝８．８Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 4-bromophenol (1.00 mmol, 173 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 3 ′, 5′-dimethyl-1,1′-biphenyl-4-ol as a colorless transparent liquid (75 mg, yield 38%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.34 (6H, s), δ 5.24 (1H, s), δ 6.86 (2H, d, J = 8.8 Hz), δ 6.94 ( 1H, s), δ 7.14 (2H, s), δ 7.44 (2H, d, J = 8.8 Hz).

  Example-37

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモベンジルアルコール（１．００ｍｍｏｌ，１８７ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、、無色透明液体の４−ヒドロキシメチル−３’，５’−ジメチル−１，１’−ビフェニルを得た（８７ｍｇ，収率４１％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．３７（６Ｈ，ｓ），δ４．７３（２Ｈ，ｓ），δ６．９９（１Ｈ，ｓ），δ７．２０（２Ｈ，ｓ），δ７．４１（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ），δ７．５７（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 4-bromobenzyl alcohol (1.00 mmol, 187 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain colorless transparent liquid 4-hydroxymethyl-3 ′, 5′-dimethyl-1,1′-biphenyl (87 mg, yield 41%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.37 (6H, s), δ 4.73 (2H, s), δ 6.99 (1H, s), δ 7.20 (2H, s), δ 7 .41 (2H, d, J = 8.5 Hz), δ 7.57 (2H, d, J = 8.5 Hz).

  Example-38

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および３，５−ビス（トリフルオロメチル）ブロモベンゼン（１．００ｍｍｏｌ，２９３ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−３，５−ジメチルベンゼン（１．００ｍｍｏｌ，１８５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３’，５’−ジメチル−３，５−ビストリフルオロメチル−１，１’−ビフェニルを得た（１８５ｍｇ，収率５８％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．４０（６Ｈ，ｓ），δ７．０９（１Ｈ，ｓ），δ７．２０（２Ｈ，ｓ），δ７．８２（１Ｈ，ｓ），δ７．９８（２Ｈ，ｓ）．
ＭＳ（ｍ／ｚ）：３１８［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 3,5-bis (trifluoromethyl) bromobenzene (1.00 mmol, 293 mg) were added at 80 ° C. Stir for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-3,5-dimethylbenzene (1.00 mmol, 185 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. for 18 hours. Stir. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 3 ′, 5′-dimethyl-3,5-bistrifluoromethyl-1,1′-biphenyl (185 mg, yield 58%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.40 (6H, s), δ 7.09 (1H, s), δ 7.20 (2H, s), δ 7.82 (1H, s), δ7 .98 (2H, s).
MS (m / z): 318 [M] ^<+> .

  Example-39

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−４−クロロベンゼン（１．００ｍｍｏｌ，１９１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモベンゾトリフルオリド（１．００ｍｍｏｌ，２２５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４−クロロ−４’−トリフルオロメチル−１，１’−ビフェニルを得た（２０５ｍｇ，収率８０％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ７．４４（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．５２（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．６５（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．７０（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4-chlorobenzene (1.00 mmol, 191 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromobenzotrifluoride (1.00 mmol, 225 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 4-chloro-4′-trifluoromethyl-1,1′-biphenyl (205 mg, yield 80%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 7.44 (2H, d, J = 8.7 Hz), δ 7.52 (2H, d, J = 8.7 Hz), δ 7.65 (2H, d , J = 8.6 Hz), δ 7.70 (2H, d, J = 8.6 Hz).

  Example-40

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−４−クロロベンゼン（１．００ｍｍｏｌ，１９１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−４−（トリフルオロメトキシ）ベンゼン（１．００ｍｍｏｌ，２４１ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４−クロロ−４’−トリフルオロメトキシ−１，１’−ビフェニルを得た（２２６ｍｇ，収率８３％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ７．２８（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ），δ７．４１（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．４８（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．５５（２Ｈ，ｄ，Ｊ＝８．５Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4-chlorobenzene (1.00 mmol, 191 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-4- (trifluoromethoxy) benzene (1.00 mmol, 241 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. Stir for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 4-chloro-4′-trifluoromethoxy-1,1′-biphenyl as a colorless transparent liquid (226 mg, yield 83%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 7.28 (2H, d, J = 8.5 Hz), δ 7.41 (2H, d, J = 8.7 Hz), δ 7.48 (2H, d , J = 8.7 Hz), δ 7.55 (2H, d, J = 8.5 Hz).

  Example-41

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−４−クロロベンゼン（１．００ｍｍｏｌ，１９１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモチオアニソール（１．００ｍｍｏｌ，２０３ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４−クロロ−４’−メチルチオ−１，１’−ビフェニルを得た（１７６ｍｇ，収率７５％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．５２（３Ｈ，ｓ）δ７．３２（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．３９（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．４８（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），７．４９（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ）．
ＭＳ（ｍ／ｚ）：２３４［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4-chlorobenzene (1.00 mmol, 191 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 4-chloro-4′-methylthio-1,1′-biphenyl as a colorless transparent liquid (176 mg, yield 75%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 2.52 (3H, s) δ 7.32 (2H, d, J = 8.7 Hz), δ 7.39 (2H, d, J = 8.7 Hz) , Δ 7.48 (2H, d, J = 8.7 Hz), 7.49 (2H, d, J = 8.7 Hz).
MS (m / z): 234 [M] ^<+> .

  Example-42

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−４−フルオロベンゼン（１．００ｍｍｏｌ，２２５ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモチオアニソール（１．００ｍｍｏｌ，２０３ｍｇ）、ジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−トリフルオロメチル−４−メチルチオ−１，１’−ビフェニルを得た（２２３ｍｇ，収率８３％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．５３（３Ｈ，ｓ），δ７．３４（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．５３（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．６８（４Ｈ，ｓ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4-fluorobenzene (1.00 mmol, 225 mg) were added and stirred at 80 ° C. for 2 hours. . 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 4′-trifluoromethyl-4-methylthio-1,1′-biphenyl (223 mg, yield 83%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ2.53 (3H, s), δ7.34 (2H, d, J = 8.6 Hz), δ7.53 (2H, d, J = 8.6 Hz) ), Δ 7.68 (4H, s).

  Example-43

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−４−トリフルオロメトキシベンゼン（１．００ｍｍｏｌ，２４１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモベンゾトリフルオリド（１．００ｍｍｏｌ，２２５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−トリフルオロメトキシ−４−トリフルオロメチル−１，１’−ビフェニルを得た（２３３ｍｇ，収率７６％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ７．３１（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．６０（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．６５（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ），δ７．７０（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4-trifluoromethoxybenzene (1.00 mmol, 241 mg) were added at 80 ° C. for 2 hours. Stir. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromobenzotrifluoride (1.00 mmol, 225 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 4′-trifluoromethoxy-4-trifluoromethyl-1,1′-biphenyl (233 mg, yield 76%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 7.31 (2H, d, J = 8.6 Hz), δ 7.60 (2H, d, J = 8.6 Hz), δ 7.65 (2H, d , J = 8.4 Hz), δ 7.70 (2H, d, J = 8.4 Hz).

  Example-44

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−４−（トリフルオロメトキシ）ベンゼン（１．００ｍｍｏｌ，２４１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモチオアニソール（１．００ｍｍｏｌ，２０３ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−トリフルオロメトキシ−４−メチルチオ−１，１’−ビフェニルを得た（２１９ｍｇ，収率７７％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．５２（３Ｈ，ｓ），δ７．２７（２Ｈ，ｄ，Ｊ＝８．８Ｈｚ），δ７．３３（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．４８（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．５６（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ）．
ＭＳ（ｍ／ｚ）：２８４［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-4- (trifluoromethoxy) benzene (1.00 mmol, 241 mg) were added at 80 ° C. Stir for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid 4′-trifluoromethoxy-4-methylthio-1,1′-biphenyl (219 mg, yield 77%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ2.52 (3H, s), δ7.27 (2H, d, J = 8.8 Hz), δ7.33 (2H, d, J = 8.6 Hz) ), Δ 7.48 (2H, d, J = 8.6 Hz), δ 7.56 (2H, d, J = 8.6 Hz).
MS (m / z): 284 [M] ^<+> .

  Example-45

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−３，４，５−トリフルオロベンゼン（１．００ｍｍｏｌ，２１１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモベンゾトリフルオリド（１．００ｍｍｏｌ，２２５ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３，４，５−トリフルオロ−４’−トリフルオロメチル−１，１’−ビフェニルを得た（２３８ｍｇ，収率８６％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ７．２０（１Ｈ，ｄ，Ｊ＝８．４Ｈｚ），δ７．２１（１Ｈ，ｄ，Ｊ＝８．４Ｈｚ），δ７．６１（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ），δ７．７１（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborol) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) were added, and the mixture was added at 80 ° C. For 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromobenzotrifluoride (1.00 mmol, 225 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 3,4,5-trifluoro-4′-trifluoromethyl-1,1′-biphenyl as a colorless transparent liquid (238 mg, yield 86%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 7.20 (1H, d, J = 8.4 Hz), δ 7.21 (1 H, d, J = 8.4 Hz), δ 7.61 (2H, d , J = 8.4 Hz), δ 7.71 (2H, d, J = 8.4 Hz).

  Example-46

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−３，４，５−トリフルオロベンゼン（１．００ｍｍｏｌ，２１１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、１−ブロモ−４−（トリフルオロメトキシ）ベンゼン（１．００ｍｍｏｌ，２４１ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３，４，５−トリフルオロ−４’−トリフルオロメトキシ−１，１’−ビフェニルを得た（２５１ｍｇ，収率８６％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ７．１５（１Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．１７（１Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ７．２９（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ），δ７．５１（２Ｈ，ｄ，Ｊ＝８．４Ｈｚ）。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborol) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) were added, and the mixture was added at 80 ° C. For 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Then potassium phosphate trihydrate (3.00 mmol, 798 mg), 1-bromo-4- (trifluoromethoxy) benzene (1.00 mmol, 241 mg) and dimethyl sulfoxide (2.0 mL) were added, and further at 80 ° C. Stir for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 3,4,5-trifluoro-4′-trifluoromethoxy-1,1′-biphenyl as a colorless transparent liquid (251 mg, yield 86%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ 7.15 (1H, d, J = 8.7 Hz), δ 7.17 (1H, d, J = 8.7 Hz), δ 7.29 (2H, d , J = 8.4 Hz), δ 7.51 (2H, d, J = 8.4 Hz).

  Example-47

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および１−ブロモ−３，４，５−トリフルオロベンゼン（１．００ｍｍｏｌ，２１１ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４−ブロモチオアニソール（１．００ｍｍｏｌ，２０３ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の３，４，５−トリフルオロ−４’−メチルチオ−１，１’−ビフェニルを得た（２０９ｍｇ，収率８２％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ２．５２（３Ｈ，ｓ），δ７．１５（１Ｈ，ｄ，Ｊ＝９．０Ｈｚ），δ７．１７（１Ｈ，ｄ，Ｊ＝９．０Ｈｚ），δ７．３１（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ），δ７．４２（２Ｈ，ｄ，Ｊ＝８．６Ｈｚ）．
ＭＳ（ｍ／ｚ）：２５４［Ｍ］^＋。

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborol) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and 1-bromo-3,4,5-trifluorobenzene (1.00 mmol, 211 mg) were added, and the mixture was added at 80 ° C. For 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Next, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4-bromothioanisole (1.00 mmol, 203 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain 3,4,5-trifluoro-4′-methylthio-1,1′-biphenyl as a colorless transparent liquid (209 mg, yield 82%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ2.52 (3H, s), δ7.15 (1H, d, J = 9.0 Hz), δ7.17 (1H, d, J = 9.0 Hz) ), Δ 7.31 (2H, d, J = 8.6 Hz), δ 7.42 (2H, d, J = 8.6 Hz).
MS (m / z): 254 [M] ^<+> .

  Example-48

アルゴン置換した反応容器に、２，２’−ビ（１，３，２−ベンゾジオキサボロール）（１．１０ｍｍｏｌ，２６２ｍｇ）、ジクロロ［１，１’−ビス（ジフェニルホスフィノ）フェロセン］パラジウム（０．０３０ｍｍｏｌ，２５ｍｇ）、酢酸カリウム（３．００ｍｍｏｌ，２９４ｍｇ）、エタノール（６．０ｍＬ）および４−ブロモ安息香酸エチル（１．００ｍｍｏｌ，２２９ｍｇ）を加えて８０℃で２時間攪拌した。得られた反応溶液に１，２−エタンジオール（２．２０ｍｍｏｌ，１３７ｍｇ）を加え、８０℃で３０分攪拌した。次いでリン酸カリウム三水和物（３．００ｍｍｏｌ，７９８ｍｇ）、４’−ブロモアセトアニリド（１．００ｍｍｏｌ，２１４ｍｇ）およびジメチルスルホキシド（２．０ｍＬ）を加え、さらに８０℃で１８時間撹拌した。反応終了後、反応混合物に水とヘキサンを加え、生成物をヘキサン層に抽出した。ヘキサン層を無水硫酸マグネシウムで乾燥後、ろ過により不溶物を除去し、ろ液を濃縮した。得られた残渣をシリカゲルクロマトグラフィーにより精製し、無色透明液体の４’−アセチルアミノ−１，１’−ビフェニル−４−カルボン酸エチルを得た（２３２ｍｇ，収率８２％）。
^１Ｈ−ＮＭＲ（４００ＭＨｚ，重クロロホルム，ｐｐｍ）：δ１．４１（３Ｈ，ｔ，Ｊ＝７．１Ｈｚ），δ２．２１（３Ｈ，ｓ），δ４．４０（２Ｈ，ｑ，Ｊ＝７．１Ｈｚ），δ７．６０（４Ｈ，ｓ），δ７．６３（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ），δ８．０９（２Ｈ，ｄ，Ｊ＝８．７Ｈｚ）．
ＭＳ（ｍ／ｚ）：２８１［Ｍ］^＋．

In a reaction vessel purged with argon, 2,2′-bi (1,3,2-benzodioxaborole) (1.10 mmol, 262 mg), dichloro [1,1′-bis (diphenylphosphino) ferrocene] palladium (0.030 mmol, 25 mg), potassium acetate (3.00 mmol, 294 mg), ethanol (6.0 mL) and ethyl 4-bromobenzoate (1.00 mmol, 229 mg) were added and stirred at 80 ° C. for 2 hours. 1,2-ethanediol (2.20 mmol, 137 mg) was added to the resulting reaction solution, and the mixture was stirred at 80 ° C. for 30 minutes. Subsequently, potassium phosphate trihydrate (3.00 mmol, 798 mg), 4′-bromoacetanilide (1.00 mmol, 214 mg) and dimethyl sulfoxide (2.0 mL) were added, and the mixture was further stirred at 80 ° C. for 18 hours. After completion of the reaction, water and hexane were added to the reaction mixture, and the product was extracted into a hexane layer. The hexane layer was dried over anhydrous magnesium sulfate, the insoluble matter was removed by filtration, and the filtrate was concentrated. The obtained residue was purified by silica gel chromatography to obtain a colorless transparent liquid ethyl 4′-acetylamino-1,1′-biphenyl-4-carboxylate (232 mg, yield 82%).
¹ H-NMR (400 MHz, deuterated chloroform, ppm): δ1.41 (3H, t, J = 7.1 Hz), δ2.21 (3H, s), δ4.40 (2H, q, J = 7.1 Hz) ), Δ 7.60 (4H, s), δ 7.63 (2H, d, J = 8.7 Hz), δ 8.09 (2H, d, J = 8.7 Hz).
MS (m / z): 281 [M] ^<+> .

Claims (7)

In the presence of a palladium catalyst and an alkali metal carboxylate, the general formula (1)

(Wherein R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) and a general formula (2)

(In the formula, R ² represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, n represents an integer of 1 to 4, where n is 2 to 4 A plurality of R ² may be the same or different, and when R ² is an alkoxy group and n is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ¹ is chlorine atom, a bromine atom, is reacted with benzene derivative A represented by.) Showing a iodine atom or a trifluoromethylsulfonyloxy group, then the general formula (3)

(In the formula, R ³ represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, m represents an integer of 1 to 4. m is an integer of 2 to 4. In this case, a plurality of R ³ may be the same or different, and when R ³ is an alkoxy group and m is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ² is a chlorine atom, a bromine atom, a benzene derivative B represented by showing a iodine atom or a trifluoromethylsulfonyloxy group.) Are reacted in the presence of an alkali metal phosphate or alkali metal carbonate The general formula (4)

(Wherein R ² , R ³ , n and m have the same contents as described above). In the presence of a palladium catalyst and an alkali metal carboxylate, the general formula (1)

(Wherein R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) and a general formula (2)

(In the formula, R ² represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, n represents an integer of 1 to 4, where n is 2 to 4 A plurality of R ² may be the same or different, and when R ² is an alkoxy group and n is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ¹ is chlorine atom, a bromine atom, after reacting the benzene derivative A represented by.) Showing a iodine atom or a trifluoromethylsulfonyloxy group, the general formula (5)

(Wherein R ⁴ and R ⁵ each independently represents a hydrogen atom or a methyl group, A represents a methylene group, a dimethylmethylene group, an ethylene group or a single bond), And general formula (3)

(In the formula, R ³ represents a hydrogen atom; a halogen atom; an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a hydroxyl group or an amino group; and 1 to carbon atoms which may be substituted with a halogen atom. 4 alkoxy groups; C 1-5 acyl groups; (C 1-4 alkoxy) carbonyl groups; hydroxyl groups; substituted with C 1-4 alkyl groups, phenyl groups, or C 2-5 acyl groups An amino group which may be substituted; (an alkyl having 1 to 4 carbon atoms which may be substituted with a fluorine atom) a thio group; or a mercapto group, m represents an integer of 1 to 4. m is an integer of 2 to 4. In this case, a plurality of R ³ may be the same or different, and when R ³ is an alkoxy group and m is 2 or more, adjacent alkoxy groups are combined to form an alkyl group having 1 to 3 carbon atoms. Forming a rangeoxy group Good .X ² is a chlorine atom, a bromine atom, a benzene derivative B represented by showing a iodine atom or a trifluoromethylsulfonyloxy group.) Are reacted in the presence of an alkali metal phosphate or alkali metal carbonate The general formula (4)

(Wherein R ² , R ³ , n and m have the same contents as described above). The production method according to claim 2, wherein the diol is 2,3-dimethyl-2,3-butanediol or 1,2-ethanediol. The production method according to claim 1, wherein R ¹ is a hydrogen atom or a tert-butyl group. The production method according to any one of claims 1 to 4, wherein the palladium catalyst is dichloro [1,1'-bis (diphenylphosphino) ferrocene] palladium. The production method according to claim 1, wherein the alkali metal carboxylate is potassium acetate or sodium acetate. The production method according to any one of claims 1 to 6, wherein the alkali metal phosphate or the alkali metal carbonate is potassium phosphate or sodium phosphate, or potassium carbonate or sodium carbonate.