JP2011195584A - Transition metal complex compound, olefin polymerizing catalyst containing the compound, and method for producing olefin polymer which is carried out in the presence of the catalyst - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a transition metal complex compound, to provide an olefin polymerizing catalyst, containing the compound, and having excellent activity, and to provide a method for producing the olefin polymer which is carried out in the presence of the catalyst.SOLUTION: There is provided the transition metal complex compound of compound 3, e.g. of chemical formula; and the olefin polymerizing catalyst including following components (A) and (B): (A) the transition metal compound; and (B) at least one compound selected from the group consisting of (B-1) an organometallic compound, (B-2) an organoaluminumoxy compound, and (B-3) a compound reactive with the transition metal compound (A), and forming an ion pair.

Description

  The present invention relates to a transition metal complex compound, an olefin multimerization catalyst containing the compound, and a method for producing an olefin multimer in the presence of the catalyst.

  α-Olefin is an important compound widely used industrially, such as a polyolefin raw material. Among them, 1-hexene is particularly in demand as a polyolefin raw material, and a highly selective production method is desired. However, most of the industrialized production methods of α-olefins are carried out using organoaluminum or a transition metal compound as a catalyst, and a mixture of α-olefins is obtained, which does not satisfy this demand. As the only selective production method of 1-hexene used industrially, an ethylene trimerization reaction using a chromium compound has been carried out (for example, see Patent Document 1), but a transition metal compound other than a chromium compound is used. There are very few techniques which manufacture 1-hexene by the ethylene trimerization reaction to be used (for example, refer patent document 2, 3, nonpatent literature 1, 2).

  In recent years, the present inventors have reported a catalyst for selectively producing 1-hexene by an ethylene trimerization reaction using a transition metal complex compound having a phenoxyimine ligand (see, for example, Patent Document 4). . However, in the existing technology, the reaction activity of the catalyst is not sufficient from the viewpoint of production cost and productivity, and further improvement of the catalyst performance has been desired.

US Pat. No. 5,856,257 JP-T-2004-524959 International Publication No. 01/68572 pamphlet International Publication No. 2009/5003 Pamphlet

Journal of American Chemical Society 2001, 123, 7423-7424 Journal of Organometallic Chemistry 2004, 689, 3643-1668.

  The present invention has been made in view of the problems of the prior art, and provides a novel transition metal complex compound and a catalyst for olefin multimerization containing the compound and having excellent activity, and the olefin. It aims at providing the manufacturing method of the olefin multimer performed in the presence of the catalyst for multimerization.

  As a result of intensive studies to solve the above problems, the present inventors have found that an olefin multimerization catalyst containing a transition metal complex compound having a specific structure has an excellent activity, and in the presence of the catalyst, an olefin In particular, when ethylene is used as the olefin, 1-hexene which is a trimer of ethylene or 1-octene which is a tetramer can be obtained with high selectivity. The present invention has been completed by finding out what can be done.

That is, the present invention relates to the following [1] to [9].
[1] A transition metal compound represented by the following general formula (1).

〔一般式（１）中、Ｍは周期律表第４〜６族の原子を表し、
Ｒ¹〜Ｒ⁵およびＲ¹⁴は、互いに同一でも異なっていてもよく、水素原子、ハロゲン原子、炭化水素基、ケイ素含有基、酸素含有基および窒素含有基から選ばれる原子または基であり、
Ｒ⁶〜Ｒ¹³は、互いに同一でも異なっていてもよく、水素原子、ハロゲン原子、炭化水素基、ケイ素含有基、酸素含有基および窒素含有基から選ばれる原子または基であって、Ｒ⁶〜Ｒ¹³の少なくとも一つがハロゲン原子であり、
Ｒ¹〜Ｒ¹⁴で示される基のうち隣接する２個の基が結合して、それらの結合する炭素原子と一緒に環を形成してもよい。

[In General Formula (1), M represents an atom of Groups 4-6 of the periodic table,
R ^{1 to} R ⁵ and R ¹⁴ may be the same or different from each other, and are atoms or groups selected from a hydrogen atom, a halogen atom, a hydrocarbon group, a silicon-containing group, an oxygen-containing group, and a nitrogen-containing group,
R ⁶ to R ¹³ may be the same or different from each other, a hydrogen atom, a halogen atom, a hydrocarbon group, an atom or radical selected from a silicon-containing group, an oxygen-containing group and a nitrogen-containing group, R ⁶ ~ At least one of R ¹³ is a halogen atom;
Two adjacent groups out of the groups represented by R ^{1 to} R ¹⁴ may be bonded to form a ring together with the carbon atoms to which they are bonded.

n represents the valence of M.
X represents a group selected from a hydrogen atom, a halogen atom, a hydrocarbon group, an oxygen-containing group and a nitrogen-containing group, and a plurality of atoms or groups represented by X may be the same or different from each other, and are represented by X A plurality of groups may be bonded to each other, and a plurality of groups represented by X may be bonded to each other to form a ring. ]

[2] The transition metal compound as described in [1], wherein at least one of R ⁶ , R ⁸ or R ^{12 in} the general formula (1) is a halogen atom.

[3] The transition metal compound as described in [2], wherein in the general formula (1), at least one of R ⁶ , R ^{8 and} R ¹² is a fluorine atom.
[4] The transition metal compound according to [2] or [3], wherein R ¹ in the general formula (1) is an alkyl group having 2 to 12 carbon atoms.

[5] In any one of [2] to [4], in the general formula (1), at least one of R ^{3 and} R ¹¹ is a hydrocarbon group having 3 to 30 carbon atoms. Transition metal compounds.
[6] The transition metal compound according to any one of [1] to [5], wherein in the general formula (1), R ² is a tertiary alkyl group or a hydrocarbon group-substituted tertiary silyl group .

[7] The transition metal compound according to any one of [1] to [6], wherein in the general formula (1), M is a titanium atom.
[8] An olefin multimerization catalyst comprising the following component (A) and component (B):
(A) Transition metal compound according to any one of [1] to [7] (B) (B-1) Organometallic compound (B-2) Organoaluminum oxy compound, and (B-3) Transition metal compound ( At least one compound selected from the group consisting of compounds that react with A) to form ion pairs.

[9] The olefin multimerization catalyst according to [8], further comprising the following component (C):
Component (C); a carrier for supporting at least one compound selected from component (A) and component (B).

  [10] A method for producing an olefin multimer, wherein the olefin is multimerized using the olefin multimerization catalyst according to [8] or [9].

  According to the present invention, it is possible to provide a specific transition metal complex compound and a highly active olefin multimerization catalyst containing the compound. Furthermore, the manufacturing method of an olefin multimer using this olefin multimerization catalyst can be provided. When the ethylene multimerization reaction is carried out by this production method, 1-hexene or 1-octene can be produced with high activity and selectivity, which is extremely valuable industrially.

It is a figure which shows the activation energy of reaction in case R < ⁶ > of General formula (1) is a hydrogen atom and a fluorine atom.

  Hereinafter, the transition metal complex compound of the present invention, the olefin multimerization catalyst, and the method for producing an olefin multimer using the olefin multimerization catalyst will be specifically described, but the present invention is not limited thereto.

In addition, in this invention, the olefin multimerization is making an olefin into a 2-10 mer.
The olefin multimerization catalyst of the present invention contains a transition metal complex compound (A) described later. In addition to the (A) transition metal complex compound, the olefin multimerization catalyst is usually (B) (b-1) an organometallic compound, (b-2) an organoaluminum oxy compound, and (b-3) (A ) It contains at least one compound selected from the group consisting of compounds that react with transition metal complex compounds to form ion pairs. In addition, the compound which reacts with (b-3) (A) transition metal complex compound to form an ion pair is also referred to as “ionized ionic compound”.

  The olefin multimerization catalyst of the present invention may contain a support (C) for supporting at least one compound selected from the group consisting of the component (A) and the component (B).

[(A) Transition metal complex compound]
The (A) transition metal complex compound of the present invention is a transition metal complex compound represented by the following general formula (1).

上記一般式（１）中、Ｒ¹〜Ｒ⁵およびＲ¹⁴は、互いに同一でも異なっていてもよく、水素原子、ハロゲン原子、炭化水素基、ケイ素含有基、酸素含有基および窒素含有基から選ばれる原子または基を示す。

In the general formula (1), R ^{1 to} R ⁵ and R ¹⁴ may be the same as or different from each other, and are selected from a hydrogen atom, a halogen atom, a hydrocarbon group, a silicon-containing group, an oxygen-containing group, and a nitrogen-containing group. Represents an atom or group.

Here, examples of the halogen atom include fluorine, chlorine, bromine, and iodine.
Specifically, the hydrocarbon group has 1 to 30 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, neopentyl, n-hexyl, preferably 1 to 20, more preferably 1 to 10 linear or branched alkyl group; vinyl, allyl, isopropenyl and the like having 2 to 30, preferably 2 to 20 carbon atoms A branched alkenyl group; a linear or branched alkynyl group having 2 to 30, preferably 2 to 20 carbon atoms such as ethynyl and propargyl; and a carbon atom number such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adamantyl 3-30, preferably 3-20, cyclic saturated hydrocarbon groups; cyclopentadienyl, indenyl A cyclic unsaturated hydrocarbon group having 5 to 30 carbon atoms such as fluorenyl; aryl having 6 to 30, preferably 6 to 20 carbon atoms such as phenyl, naphthyl, biphenyl, terphenyl, phenanthryl, anthracenyl, etc. Groups; alkyl-substituted aryl groups such as tolyl, isopropylphenyl, tert-butylphenyl, dimethylphenyl, and di-tert-butylphenyl; alkylidene having 1 to 30, preferably 5 to 10 carbon atoms such as benzylidene, methylidene, and ethylidene Group and the like.

  In the above hydrocarbon group, a hydrogen atom may be substituted with a halogen. For example, a halogenated hydrocarbon group having 1 to 30 carbon atoms, preferably 1 to 20 carbon atoms such as trifluoromethyl, pentafluorophenyl, chlorophenyl and the like. Can be mentioned.

  In the hydrocarbon group, a hydrogen atom may be substituted with another hydrocarbon group, and examples thereof include aryl group-substituted alkyl groups such as benzyl, cumyl, diphenylethyl, and trityl.

  Further, the hydrocarbon group includes residues such as nitrogen-containing compounds such as pyrrole, pyridine, pyrimidine, quinoline and triazine, oxygen-containing compounds such as furan and pyran, sulfur-containing compounds such as thiophene, and heterocyclic compounds thereof. A heterocyclic compound residue such as a group further substituted with a substituent such as an alkyl group or alkoxy group having 1 to 30, preferably 1 to 20 carbon atoms in the residue; alkoxy group, aryloxy group, ester group, ether Group, acyl group, carboxyl group, carbonate group, hydroxy group, peroxy group, carboxylic anhydride group and other oxygen-containing groups; amino group, imino group, amide group, imide group, hydrazino group, hydrazono group, nitro group, nitroso Group, cyano group, isocyano group, cyanate ester group, amidino group, diazo group, amino group Nitrogen-containing groups such as those formed into nium salts; Boron-containing groups such as boranediyl group, boranetriyl group, diboranyl group; mercapto group, thioester group, dithioester group, alkylthio group, arylthio group, thioacyl group, thioether group, thiocyanic acid Sulfur-containing groups such as ester groups, isothiocyanate groups, sulfone ester groups, sulfonamido groups, thiocarboxyl groups, dithiocarboxyl groups, sulfo groups, sulfonyl groups, sulfinyl groups, sulfenyl groups; phosphide groups, phosphoryl groups, thiophosphoryls And a phosphorus-containing group such as a phosphato group, a silicon-containing group, a germanium-containing group, or a tin-containing group.

  Among these, in particular, 1 to 30 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, neopentyl, n-hexyl, adamantyl, etc. 20, more preferably 1-10, more preferably 2-10 linear or branched alkyl groups; phenyl, naphthyl, biphenyl, terphenyl, phenanthryl, anthracenyl, etc. 6-30, preferably 6. An aryl group having ˜20; a halogen atom, an alkyl group or alkoxy group having 1 to 30 carbon atoms, preferably 1 to 20 carbon atoms, an aryl group or aryloxy having 6 to 30 carbon atoms, preferably 6 to 20 carbon atoms; A substituted aryl group substituted with 1 to 5 substituents such as a group is preferred.

  Examples of the silicon-containing group include a silyl group, a siloxy group, a hydrocarbon-substituted silyl group, and a hydrocarbon-substituted siloxy group. Specific examples of the hydrocarbon-substituted silyl group include methylsilyl, dimethylsilyl, trimethylsilyl, ethylsilyl, diethylsilyl, triethylsilyl, diphenylmethylsilyl, triphenylsilyl, dimethylphenylsilyl, dimethyl-tert-butylsilyl, dimethyl (pentafluoro Phenyl) silyl and the like. Among these, methylsilyl, dimethylsilyl, trimethylsilyl, ethylsilyl, diethylsilyl, triethylsilyl, dimethylphenylsilyl, triphenylsilyl and the like are preferable. In particular, trimethylsilyl, triethylsilyl, triphenylsilyl, and dimethylphenylsilyl are preferable. Specific examples of the hydrocarbon-substituted siloxy group include trimethylsiloxy and the like.

Examples of the oxygen-containing group and the nitrogen-containing group include the same groups as those exemplified as the substituent which may be contained in the hydrocarbon group.
R ^{1 to} R ⁵ and R ¹⁴ are each a hydrogen atom, a halogen atom, a hydrocarbon group having 1 to 30 carbon atoms, a hydrocarbon from the viewpoint of catalytic performance and ease of production when used as an olefin multimerization catalyst. A substituted silyl group is preferred.

Among these, preferred groups as R ¹ are hydrocarbon groups having 1 to 20 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, cyclohexyl, and n-octyl among the above examples. More preferably, it is a hydrocarbon group having 1 to 12 carbon atoms, and methyl, ethyl, n-propyl and n-butyl are particularly preferred from the viewpoint of catalytic activity and selectivity.

Among the above examples, preferred groups as R ² are tertiary alkyl groups having 4 to 20 carbon atoms such as tert-butyl, adamantyl, cumyl, and trityl; carbons such as trimethylsilyl, methyldiphenylsilyl, dimethylphenylsilyl, and triphenylsilyl. It is a hydrocarbon-substituted tertiary silyl group having 3 to 20 atoms.

Preferred examples of R ³ include isopropyl, cyclohexyl, tert-butyl, adamantyl, cumyl, trityl, phenyl, tolyl, dimethylphenyl, trimethylphenyl, ethylphenyl, propylphenyl, biphenyl, naphthyl, methylnaphthyl, among the above examples. A hydrocarbon group having 3 to 20 carbon atoms such as anthracenyl and phenanthryl; a hydrocarbon-substituted silyl group having 1 to 20 carbon atoms such as trimethylsilyl, methyldiphenylsilyl, dimethylphenylsilyl, and triphenylsilyl.

In the general formula (1), R ^{6 to} R ¹³ may be the same or different from each other, and an atom selected from a hydrogen atom, a halogen atom, a hydrocarbon group, a silicon-containing group, an oxygen-containing group, and a nitrogen-containing group or And at least one of R ^{6 to} R ¹³ represents a halogen atom.

Note that the halogen atom, hydrocarbon group, silicon-containing group, oxygen-containing group and nitrogen-containing group selected in R ^{6 to} R ¹³ are the same as R ^{1 to} R ⁵ and R ^{14 in the} general formula (1). Things.

Specifically, the halogen atom includes fluorine, chlorine, bromine and iodine.
Specifically, the hydrocarbon group has 1 to 30 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, neopentyl, n-hexyl, preferably 1 to 20, more preferably 1 to 10 linear or branched alkyl group; vinyl, allyl, isopropenyl and the like having 2 to 30, preferably 2 to 20 carbon atoms A branched alkenyl group; a linear or branched alkynyl group having 2 to 30, preferably 2 to 20 carbon atoms such as ethynyl and propargyl; and a carbon atom number such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adamantyl 3-30, preferably 3-20, cyclic saturated hydrocarbon groups; cyclopentadienyl, indenyl A cyclic unsaturated hydrocarbon group having 5 to 30 carbon atoms such as fluorenyl; aryl having 6 to 30, preferably 6 to 20 carbon atoms such as phenyl, naphthyl, biphenyl, terphenyl, phenanthryl, anthracenyl, etc. Groups; alkyl-substituted aryl groups such as tolyl, isopropylphenyl, tert-butylphenyl, dimethylphenyl, and di-tert-butylphenyl; alkylidene having 1 to 30, preferably 5 to 10 carbon atoms such as benzylidene, methylidene, and ethylidene Group and the like.

  In the above hydrocarbon group, a hydrogen atom may be substituted with a halogen. For example, a halogenated hydrocarbon group having 1 to 30 carbon atoms, preferably 1 to 20 carbon atoms such as trifluoromethyl, pentafluorophenyl, chlorophenyl and the like. Can be mentioned.

  In the hydrocarbon group, a hydrogen atom may be substituted with another hydrocarbon group, and examples thereof include aryl group-substituted alkyl groups such as benzyl, cumyl, diphenylethyl, and trityl.

  Further, the hydrocarbon group includes residues such as nitrogen-containing compounds such as pyrrole, pyridine, pyrimidine, quinoline and triazine, oxygen-containing compounds such as furan and pyran, sulfur-containing compounds such as thiophene, and heterocyclic compounds thereof. A heterocyclic compound residue such as a group further substituted with a substituent such as an alkyl group or alkoxy group having 1 to 30, preferably 1 to 20 carbon atoms in the residue; alkoxy group, aryloxy group, ester group, ether Group, acyl group, carboxyl group, carbonate group, hydroxy group, peroxy group, carboxylic anhydride group and other oxygen-containing groups; amino group, imino group, amide group, imide group, hydrazino group, hydrazono group, nitro group, nitroso Group, cyano group, isocyano group, cyanate ester group, amidino group, diazo group, amino group Nitrogen-containing groups such as those formed into nium salts; Boron-containing groups such as boranediyl group, boranetriyl group, diboranyl group; mercapto group, thioester group, dithioester group, alkylthio group, arylthio group, thioacyl group, thioether group, thiocyanic acid Sulfur-containing groups such as ester groups, isothiocyanate groups, sulfone ester groups, sulfonamido groups, thiocarboxyl groups, dithiocarboxyl groups, sulfo groups, sulfonyl groups, sulfinyl groups, sulfenyl groups; phosphide groups, phosphoryl groups, thiophosphoryls And a phosphorus-containing group such as a phosphato group, a silicon-containing group, a germanium-containing group, or a tin-containing group.

  Examples of the silicon-containing group include a silyl group, a siloxy group, a hydrocarbon-substituted silyl group, and a hydrocarbon-substituted siloxy group. Specific examples of the hydrocarbon-substituted silyl group include methylsilyl, dimethylsilyl, trimethylsilyl, ethylsilyl, diethylsilyl, triethylsilyl, diphenylmethylsilyl, triphenylsilyl, dimethylphenylsilyl, dimethyl-tert-butylsilyl, dimethyl (pentafluoro Phenyl) silyl and the like. Among these, methylsilyl, dimethylsilyl, trimethylsilyl, ethylsilyl, diethylsilyl, triethylsilyl, dimethylphenylsilyl, triphenylsilyl and the like are preferable. In particular, trimethylsilyl, triethylsilyl, triphenylsilyl, and dimethylphenylsilyl are preferable. Specific examples of the hydrocarbon-substituted siloxy group include trimethylsiloxy and the like.

Examples of the oxygen-containing group and the nitrogen-containing group include the same groups as those exemplified as the substituent which may be contained in the hydrocarbon group.
In the general formula (1), at least one of R ^{6 to} R ¹³ is preferably a halogen atom. Specific examples of the halogen atom include fluorine, chlorine, bromine and iodine.

From the viewpoint of catalytic activity when used as an olefin multimerization catalyst, it is preferred that at least one of R ⁶ , R ⁸ or R ¹² among R ^{6 to} R ¹³ is a halogen atom, and R ⁶ , R ⁸ or It is particularly preferred that at least one of R ¹² is a fluorine atom.

Introducing a halogen atom into at least one of R ⁶ , R ^8, or R ¹² means changing the electronic state of the metal center of the transition metal compound through the phenoxyimine ligand. It is presumed that the reactivity is improved by changing the stability.

Such an increase in the reaction rate due to the introduction of the halogen atom is supported also from the activation energy of the reaction obtained using the density functional method (B3LYP / LANL2DZ). This will be described below by taking the difference in the type of substituent of R ^{6 as} an example. As shown in FIG. 1, when R ⁶ is a fluorine atom, the activation energy of the rate-limiting reaction of the catalytic trimerization reaction is ΔE ‡ = 59.8 kJ / mol, and R ⁶ is a hydrogen atom It is 2.8 kJ / mol lower than (ΔE ‡ = 62.6 kJ / mol). Since the reaction rate constant k is determined by the Arrhenius equation: k = A · exp (−E / RT) (A: reaction frequency factor, R: gas constant) as a function of reaction activation energy and temperature, the frequency Assuming that the factors A are the same, in the reaction at 20 ° C., the ratio of the reaction rate constant k _F when R ⁶ is a fluorine atom to the rate constant k _H when R ⁶ is a hydrogen atom is approximately 3: 1, ie, the reaction rate is expected to be almost tripled. As will be described later, by using such a transition metal compound as an olefin multimerization catalyst, the reactivity of the catalyst increases, and favorable results are obtained from the viewpoint of reaction activity.

Regarding preferred embodiments of other substituents when at least one of R ⁶ , R ⁸ or R ¹² is a halogen atom, preferred groups as R ¹ are ethyl, n-propyl, isopropyl, n-butyl, n-hexyl, It is a hydrocarbon group having 2 to 12 carbon atoms such as cyclohexyl and n-octyl, and ethyl, n-propyl and n-butyl are particularly preferred from the viewpoint of catalytic activity and selectivity.

When at least one of R ⁶ , R ⁸ or R ¹² is a halogen atom, R ³ and R ¹¹ may be the same or different from each other, but at least one of them is a hydrocarbon having 3 to 30 carbon atoms. It is preferably a group. Specific examples of the hydrocarbon group having 3 to 30 carbon atoms include n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, neopentyl, n-hexyl and the like having 3 to 30 carbon atoms. , Preferably a linear or branched alkyl group having 3 to 20; a linear or branched alkenyl group having 3 to 30 carbon atoms, preferably 3 to 20, such as allyl or isopropenyl; A linear or branched alkynyl group having 3 to 30, preferably 3 to 20 carbon atoms such as propargyl; 3 to 30 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adamantyl, preferably 3 to 20 cyclic saturated hydrocarbon groups; 5 to 30 carbon atoms such as cyclopentadienyl, indenyl, fluorenyl, etc. Cyclic unsaturated hydrocarbon group; aryl group having 6 to 30 carbon atoms, preferably 6 to 20 carbon atoms, such as phenyl, naphthyl, biphenyl, terphenyl, phenanthryl, anthracenyl; tolyl, isopropylphenyl, tert-butylphenyl Alkyl substituted aryl groups such as dimethylphenyl and di-tert-butylphenyl; alkylidene groups having 3 to 30, preferably 5 to 20 carbon atoms such as benzylidene, methylidene and ethylidene.

  In the hydrocarbon group, a hydrogen atom may be substituted with a halogen. For example, a halogenated hydrocarbon group having 3 to 30 carbon atoms, preferably 3 to 20 carbon atoms such as perfluorobutyl, pentafluorophenyl, and chlorophenyl. Can be mentioned.

  In the hydrocarbon group, a hydrogen atom may be substituted with another hydrocarbon group, and examples thereof include aryl group-substituted alkyl groups such as benzyl, cumyl, diphenylethyl, and trityl.

  Further, the hydrocarbon group includes residues such as nitrogen-containing compounds such as pyrrole, pyridine, pyrimidine, quinoline and triazine, oxygen-containing compounds such as furan and pyran, sulfur-containing compounds such as thiophene, and heterocyclic compounds thereof. A heterocyclic compound residue such as a group further substituted with a substituent such as an alkyl group or alkoxy group having 1 to 30, preferably 1 to 20 carbon atoms in the residue; alkoxy group, aryloxy group, ester group, ether Group, acyl group, carboxyl group, carbonate group, hydroxy group, peroxy group, carboxylic anhydride group and other oxygen-containing groups; amino group, imino group, amide group, imide group, hydrazino group, hydrazono group, nitro group, nitroso Group, cyano group, isocyano group, cyanate ester group, amidino group, diazo group, amino group Nitrogen-containing groups such as those formed into nium salts; Boron-containing groups such as boranediyl group, boranetriyl group, diboranyl group; mercapto group, thioester group, dithioester group, alkylthio group, arylthio group, thioacyl group, thioether group, thiocyanic acid Sulfur-containing groups such as ester groups, isothiocyanate groups, sulfone ester groups, sulfonamido groups, thiocarboxyl groups, dithiocarboxyl groups, sulfo groups, sulfonyl groups, sulfinyl groups, sulfenyl groups; phosphide groups, phosphoryl groups, thiophosphoryls And a phosphorus-containing group such as a phosphato group, a silicon-containing group, a germanium-containing group, or a tin-containing group.

Among these, when at least one of R ⁶ , R ⁸ or R ¹² is a halogen atom, the substituent selected as R ³ and R ¹¹ is particularly preferably isopropyl, cyclohexyl, tert-butyl, adamantyl, cumyl, Examples include trityl, phenyl, tolyl, dimethylphenyl, trimethylphenyl, ethylphenyl, propylphenyl, biphenyl, naphthyl, methylnaphthyl, anthracenyl, and phenanthryl.

When at least one of R ⁶ , R ⁸ or R ¹² is a halogen atom, R ⁴ , R ⁵ , R ⁹ and R ¹⁰ are preferably hydrogen atoms at the same time, and R ⁷ and R ¹³ are hydrocarbon groups. Is preferably 1 or 2 carbon atoms.

Furthermore, two or more of the groups represented by R ^{1 to} R ¹⁴ may be linked to each other. Preferably, adjacent groups may be linked to each other to form an alicyclic ring, an aromatic ring, or a hydrocarbon ring containing a different atom such as an oxygen atom or a nitrogen atom, and these rings further have a substituent. May be.

  In the general formula (1), M represents a transition metal atom in Groups 4 to 6 of the periodic table, and n represents the valence of M. Preferable examples of M include titanium, zirconium, hafnium, vanadium, tantalum, and chromium. M is more preferably a transition metal atom of Group 4 of the periodic table such as titanium, zirconium, hafnium, etc., and titanium is particularly preferable. n is particularly preferably 4 for Group 4 transition metal atoms such as titanium, zirconium, hafnium, 3-5 for vanadium and tantalum, and 3 for chromium.

  In the general formula (1), X represents a hydrogen atom, a halogen atom, a hydrocarbon group, an oxygen-containing group or a nitrogen-containing group. The atoms and groups represented by X may be the same or different from each other, and the groups represented by X may be bonded to each other to form a ring.

Here, examples of the halogen atom, hydrocarbon group, oxygen-containing group and nitrogen-containing group selected in X include the same as those exemplified for R ^{1 to} R ¹⁴ in the general formula (1).
Specifically, the halogen atom includes fluorine, chlorine, bromine and iodine.

  Specifically, the hydrocarbon group has 1 to 30 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, neopentyl, n-hexyl, preferably 1 to 20, more preferably 1 to 10 linear or branched alkyl group; vinyl, allyl, isopropenyl and the like having 2 to 30, preferably 2 to 20 carbon atoms A branched alkenyl group; a linear or branched alkynyl group having 2 to 30, preferably 2 to 20 carbon atoms such as ethynyl and propargyl; and a carbon atom number such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and adamantyl 3-30, preferably 3-20, cyclic saturated hydrocarbon groups; cyclopentadienyl, inde A cyclic unsaturated hydrocarbon group having 5 to 30 carbon atoms such as ru and fluorenyl; aryl having 6 to 30 carbon atoms, preferably 6 to 20 carbon atoms such as phenyl, naphthyl, biphenyl, terphenyl, phenanthryl, anthracenyl, etc. ) Groups; alkyl-substituted aryl groups such as tolyl, isopropylphenyl, tert-butylphenyl, dimethylphenyl, di-tert-butylphenyl; benzylidene, methylidene, ethylidene, etc. having 1 to 30, preferably 5 to 10 carbon atoms And an alkylidene group.

  In the above hydrocarbon group, a hydrogen atom may be substituted with a halogen. For example, a halogenated hydrocarbon group having 1 to 30 carbon atoms, preferably 1 to 20 carbon atoms such as trifluoromethyl, pentafluorophenyl, chlorophenyl and the like. Can be mentioned.

  In the hydrocarbon group, a hydrogen atom may be substituted with another hydrocarbon group, and examples thereof include aryl group-substituted alkyl groups such as benzyl, cumyl, diphenylethyl, and trityl.

  Further, the hydrocarbon group includes residues such as nitrogen-containing compounds such as pyrrole, pyridine, pyrimidine, quinoline and triazine, oxygen-containing compounds such as furan and pyran, sulfur-containing compounds such as thiophene, and heterocyclic compounds thereof. A heterocyclic compound residue such as a group further substituted with a substituent such as an alkyl group or alkoxy group having 1 to 30, preferably 1 to 20 carbon atoms in the residue; alkoxy group, aryloxy group, ester group, ether Group, acyl group, carboxyl group, carbonate group, hydroxy group, peroxy group, carboxylic anhydride group and other oxygen-containing groups; amino group, imino group, amide group, imide group, hydrazino group, hydrazono group, nitro group, nitroso Group, cyano group, isocyano group, cyanate ester group, amidino group, diazo group, amino group Nitrogen-containing groups such as those formed into nium salts; Boron-containing groups such as boranediyl group, boranetriyl group, diboranyl group; mercapto group, thioester group, dithioester group, alkylthio group, arylthio group, thioacyl group, thioether group, thiocyanic acid Sulfur-containing groups such as ester groups, isothiocyanate groups, sulfone ester groups, sulfonamido groups, thiocarboxyl groups, dithiocarboxyl groups, sulfo groups, sulfonyl groups, sulfinyl groups, sulfenyl groups; phosphide groups, phosphoryl groups, thiophosphoryls And a phosphorus-containing group such as a phosphato group, a silicon-containing group, a germanium-containing group, or a tin-containing group.

Examples of the oxygen-containing group and the nitrogen-containing group include the same groups as those exemplified as the substituent which may be contained in the hydrocarbon group.
Among these, X is preferably a halogen atom or an alkyl group, and more preferably a chlorine, bromine or methyl group.

  The synthesis of the transition metal complex compound (A) represented by the general formula (1) of the present invention can be performed in accordance with, for example, the method described in Journal of Organometallic Chemistry 2003, 678, pages 134-141. .

  The reaction product obtained by the method described in the above document can be used as a catalyst for olefin multimerization without any purification operation after the reaction, but it can be used after purification by a purification operation such as recrystallization. It is preferable.

  In addition, in this invention, when describing as (A) transition metal complex compound, the transition metal complex compound represented by the said general formula (I) is included.

[Olefin multimerization catalyst]
In addition to the above (A) transition metal complex compound, the olefin multimerization catalyst of the present invention is usually
(B) (b-1) an organometallic compound,
It contains at least one compound selected from the group consisting of (b-2) an organoaluminum oxy compound, and (b-3) (A) a compound that reacts with a transition metal complex compound to form an ion pair.

  Hereinafter, (b-1) an organometallic compound, (b-2) an organoaluminum oxy compound, and (b-3) (A) a compound that forms an ion pair by reacting with a transition metal complex compound will be described.

[(B-1) Organometallic compound]
Specific examples of the organometallic compound (b-1) used as necessary in the present invention include the following organometallic compounds of Groups 1, 2 and 12, 13 of the periodic table. Examples thereof include (b-1a), (b-1b), and (b-1c) described below. In the present invention, the (b-1) organometallic compound does not include the (b-2) organoaluminum oxy compound described later.

(B-1a) formula R ^a _m Al (OR ^b) an organic aluminum compound represented by _n H _p X _q.
(In the formula, R ^a and R ^b each represent a hydrocarbon group having 1 to 15, preferably 1 to 4 carbon atoms which may be the same or different from each other, X represents a halogen atom, and m represents 0 < m ≦ 3, n is 0 ≦ n <3, p is 0 ≦ p <3, q is a number of 0 ≦ q <3, and m + n + p + q = 3)
(B-1b) Complex alkylated product of Group 1 metal of the periodic table represented by the general formula M ² AlR ^a ₄ and aluminum.
(Wherein M ² represents Li, Na or K, and R ^a represents a hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 4 carbon atoms)
(B-1c) A dialkyl compound of Group 2 or Group 12 metal represented by the general formula R ^a R ^b M ³ .
(In the formula, R ^a and R ^b each represent a hydrocarbon group having 1 to 15, preferably 1 to 4 carbon atoms, which may be the same or different from each other, and M ³ is Mg, Zn or Cd)
Examples of the organoaluminum compound belonging to (b-1a) include the following compounds.

General formula R ^a _m Al (OR ^b ) _3-m (wherein R ^a and R ^b represent a hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 4 carbon atoms, which may be the same or different from each other. M is preferably a number of 1.5 ≦ m ≦ 3.), An organoaluminum compound represented by the general formula R ^a _m AlX _3-m (wherein R ^a is 1 to 1 carbon atoms) 15, preferably 1 to 4 hydrocarbon groups, X represents a halogen atom, and m is preferably 0 <m <3.) An organoaluminum compound represented by the general formula R ^a _m AlH _{3− m} (wherein R ^a represents a hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 4 carbon atoms, and m is preferably 2 ≦ m <3), a general formula during _{^{R a m Al (oR b)}} n X q ( wherein, R ^a and R ^b are optionally carbon atoms be the same or different from each other 1 15, preferably 1 to 4 hydrocarbon groups, X represents a halogen atom, m is 0 <m ≦ 3, n is 0 ≦ n <3, q is a number 0 ≦ q <3, and m + n + q = 3).

More specifically, as the organoaluminum compound belonging to (b-1a), trimethylaluminum, triethylaluminum, tri (n-butyl) aluminum, tripropylaluminum, tripentylaluminum, trihexylaluminum, trioctylaluminum, tridecyl Tri (n-alkyl) aluminum such as aluminum; triisopropylaluminum, triisobutylaluminum, tri (sec-butyl) aluminum, tri (tert-butyl) aluminum, tri (2-methylbutyl) aluminum, tri (3-methylbutyl) aluminum , Tri (2-methylpentyl) aluminum, tri (3-methylpentyl) aluminum, tri (4-methylpentyl) aluminum, tri (2-methylhexyl) Tri-branched alkylaluminums such as aluminum, tri (3-methylhexyl) aluminum, tri (2-ethylhexyl) aluminum; tricycloalkylaluminums such as tricyclohexylaluminum and tricyclooctylaluminum; triaryl aluminum diethyl hydride, dialkylaluminum hydride such as diisobutylaluminum _{hydride; (iC 4 H 9) x} Al y (C 5 H 10) z ( wherein, x, y, z are each a positive number, z ≧ 2x .iC ₄ H ₉ is represents a isobutyl group) alkenyl aluminum such as isoprenyl aluminum represented by like;. triisobutylaluminum methoxide, isobutyl Arumini Muetokishido, alkylaluminum alkoxides such as isobutylaluminum isopropoxide; alkyl sesquichloride alkoxides such as ethyl aluminum sesqui ethoxide, butyl aluminum sesqui butoxide; dimethyl aluminum methoxide, diethyl aluminum ethoxide, dialkylaluminum alkoxides such as dibutyl aluminum butoxide R ^a _2.5 Al (OR ^b ) _0.5 (wherein, R ^a and R ^b represent a hydrocarbon group having 1 to 15 carbon atoms, which may be the same as or different from each other, preferably 1 to 4). Partially alkoxylated alkylaluminum having an average composition represented; diethylaluminum phenoxide, diethylaluminum (2,6-di-tert-butyl 4-methylpheno) Sid), ethylaluminum bis (2,6-di-tert-butyl 4-methylphenoxide), diisobutylaluminum (2,6-di-tert-butyl 4-methylphenoxide), isobutylaluminum bis (2,6-di-) dialkylaluminum aryloxides such as tert-butyl 4-methylphenoxide); dialkylaluminum halides such as dimethylaluminum chloride, diethylaluminum chloride, dibutylaluminum chloride, diethylaluminum bromide, diisobutylaluminum chloride; ethylaluminum sesquichloride, butylaluminum sesquichloride Alkyl aluminum sesquihalides such as ethyl aluminum sesquibromide; ethyl aluminum dichloride, propyl al Partially halogenated alkylaluminums such as alkylaluminum dihalides such as nium dichloride and butylaluminum dibromide; Dialkylaluminum hydrides such as diethylaluminum hydride and dibutylaluminum hydride; Alkyl such as ethylaluminum dihydride and propylaluminum dihydride Other partially hydrogenated alkylaluminums such as aluminum dihydride; and partially alkoxylated and halogenated alkylaluminums such as ethylaluminum ethoxy chloride, butylaluminum butoxycyclyl, ethylaluminum ethoxybromide and the like.

Moreover, the compound similar to (b-1a) can also be used, for example, the organoaluminum compound which two or more aluminum compounds couple | bonded through the nitrogen atom is mentioned. Specific examples of such a compound include (C ₂ H ₅ ) ₂ AlN (C ₂ H ₅ ) Al (C ₂ H ₅ ) ₂ .

Examples of the compound belonging to (b-1b) include LiAl (C ₂ H ₅ ) ₄ and LiAl (C ₇ H ₁₅ ) ₄ .
Examples of the compound belonging to (b-1c) include dimethylmagnesium, diethylmagnesium, dibutylmagnesium, and butylethylmagnesium.

  As (b-1) organometallic compounds other than the above (b-1a) to (b-1c), methyllithium, ethyllithium, propyllithium, butyllithium, methylmagnesium bromide, methylmagnesium chloride, ethylmagnesium bromide, ethyl Magnesium chloride, propylmagnesium bromide, propylmagnesium chloride, butylmagnesium bromide, butylmagnesium chloride and the like can also be used.

  A compound that can form the organoaluminum compound in the multimerization reaction system, such as a combination of an aluminum halide and an alkyl lithium, or a combination of an aluminum halide and an alkyl magnesium, can also be used.

  (B-1) Among organometallic compounds, organoaluminum compounds are preferred. The above (b-1) organometallic compounds are used singly or in combination of two or more.

[(B-2) Organoaluminum oxy compound]
The (b-2) organoaluminum oxy compound used as necessary in the present invention may be a conventionally known aluminoxane, or a benzene insoluble organoaluminum as exemplified in JP-A-2-78687. It may be an oxy compound.

  A conventionally well-known aluminoxane can be manufactured, for example with the following method, and is normally obtained as a solution of a hydrocarbon solvent. (1) Compounds containing adsorbed water or salts containing water of crystallization, such as magnesium chloride hydrate, copper sulfate hydrate, aluminum sulfate hydrate, nickel sulfate hydrate, first cerium chloride hydrate, etc. A method of reacting adsorbed water or crystal water with an organoaluminum compound by adding an organoaluminum compound such as trialkylaluminum to the suspension of the hydrocarbon. (2) A method of allowing water, ice or water vapor to act directly on an organoaluminum compound such as trialkylaluminum in a medium such as benzene, toluene, ethyl ether or tetrahydrofuran. (3) A method in which an organotin oxide such as dimethyltin oxide or dibutyltin oxide is reacted with an organoaluminum compound such as trialkylaluminum in a medium such as decane, benzene, or toluene.

  The aluminoxane may contain a small amount of an organometallic component. Further, after removing the solvent or the unreacted organoaluminum compound from the recovered aluminoxane solution by distillation, it may be redissolved in a solvent or suspended in a poor aluminoxane solvent.

  Specific examples of the organoaluminum compound used when preparing the aluminoxane include the same organoaluminum compounds as those exemplified as the organoaluminum compound belonging to (b-1a).

Of these, trialkylaluminum and tricycloalkylaluminum are preferable, and trimethylaluminum is particularly preferable.
The organoaluminum compounds as described above are used singly or in combination of two or more.

  Solvents used for the preparation of aluminoxane include aromatic hydrocarbons such as benzene, toluene, xylene, cumene, and cymene, aliphatic hydrocarbons such as pentane, hexane, heptane, octane, decane, dodecane, hexadecane, and octadecane, and cyclopentane. , Cycloaliphatic hydrocarbons such as cyclohexane, cyclooctane and methylcyclopentane, petroleum fractions such as gasoline, kerosene and light oil, or halides of the above aromatic hydrocarbons, aliphatic hydrocarbons and alicyclic hydrocarbons, especially chlorine And hydrocarbon solvents such as bromide and bromide. Furthermore, ethers such as ethyl ether and tetrahydrofuran can also be used. Of these solvents, aromatic hydrocarbons or aliphatic hydrocarbons are particularly preferable.

  The benzene-insoluble organoaluminum oxy compound used in the present invention has an Al component dissolved in benzene at 60 ° C. of usually 10% or less, preferably 5% or less, particularly preferably 2% or less in terms of Al atom, That is, those which are insoluble or hardly soluble in benzene are preferred.

  Examples of the organoaluminum oxy compound used in the present invention also include an organoaluminum oxy compound containing boron represented by the following general formula (i).

式中、Ｒ¹⁵は炭素原子数が１〜１０の炭化水素基を示す。Ｒ¹⁶は、互いに同一でも異なっていてもよい水素原子、ハロゲン原子、炭素原子数が１〜１０の炭化水素基を示す。

In the formula, R ¹⁵ represents a hydrocarbon group having 1 to 10 carbon atoms. R ¹⁶ represents a hydrogen atom, a halogen atom, or a hydrocarbon group having 1 to 10 carbon atoms, which may be the same as or different from each other.

The organoaluminum oxy compound containing boron represented by the general formula (i) includes an alkyl boronic acid represented by the following general formula (ii) and an organoaluminum compound in an inert solvent under an inert gas atmosphere. It can be produced by reacting at a temperature of -80 ° C to room temperature for 1 minute to 24 hours.
R ¹⁵ -B (OH) ₂ (ii)
(Wherein R ¹⁵ represents the same group as described above)

  Specific examples of the alkyl boronic acid represented by the general formula (ii) include methyl boronic acid, ethyl boronic acid, isopropyl boronic acid, n-propyl boronic acid, n-butyl boronic acid, isobutyl boronic acid, and n-hexyl boron. Examples include acid, cyclohexyl boronic acid, phenyl boronic acid, 3,5-difluorophenyl boronic acid, pentafluorophenyl boronic acid, 3,5-bis (trifluoromethyl) phenyl boronic acid, and the like. Among these, methyl boronic acid, n-butyl boronic acid, isobutyl boronic acid, 3,5-difluorophenyl boronic acid, and pentafluorophenyl boronic acid are preferable.

These may be used alone or in combination of two or more.
Specific examples of the organoaluminum compound to be reacted with the alkylboronic acid include the same organoaluminum compounds as those exemplified as the organoaluminum compound belonging to (b-1a). Of these, trialkylaluminum and tricycloalkylaluminum are preferable, and trimethylaluminum, triethylaluminum, and triisobutylaluminum are particularly preferable. These may be used alone or in combination of two or more.

  The above (b-2) organoaluminum oxy compounds are used singly or in combination of two or more.

[(B-3) Ionized ionic compound]
(B-3) (A) A compound that reacts with a transition metal complex compound to form an ion pair, which is used as necessary in the present invention, reacts with (A) a transition metal complex compound to form an ion pair. A compound. Therefore, what forms an ion pair by making it contact with at least (A) transition metal complex compound is contained in this compound.

  Examples of such compounds include JP-A-1-501950, JP-A-1-502036, JP-A-3-179905, JP-A-3-179006, JP-A-3-207703, and JP-A-3. And Lewis acids, ionic compounds, borane compounds and carborane compounds described in US Pat. No. 207704 and US Pat. No. 5,321,106. Furthermore, heteropoly compounds and isopoly compounds can also be mentioned.

Specifically, as the Lewis acid, a compound represented by BR ₃ (R is a phenyl group or fluorine which may have a substituent such as fluorine, methyl group or trifluoromethyl group) can be mentioned. For example, trifluoroboron, triphenylboron, tris (4-fluorophenyl) boron, tris (3,5-difluorophenyl) boron, tris (4-fluoromethylphenyl) boron, tris (pentafluorophenyl) boron, tris (P-Tolyl) boron, tris (o-tolyl) boron, tris (3,5-dimethylphenyl) boron and the like can be mentioned.

  Examples of the ionic compound include compounds represented by the following general formula (III).

式中、Ｒ¹⁷⁺としては、Ｈ⁺、カルボニウムカチオン、オキソニウムカチオン、アンモニウムカチオン、ホスホニウムカチオン、シクロヘプチルトリエニルカチオン、遷移金属を有するフェロセニウムカチオンなどが挙げられる。

In the formula, ^examples of R ¹⁷⁺ include H ⁺ , carbonium cation, oxonium cation, ammonium cation, phosphonium cation, cycloheptyltrienyl cation, and ferrocenium cation having a transition metal.

R ^{18 to} R ²¹ are organic groups which may be the same as or different from each other, preferably an aryl group or a substituted aryl group.
Specific examples of the carbonium cation include trisubstituted carbonium cations such as triphenylcarbonium cation, tri (methylphenyl) carbonium cation, and tri (dimethylphenyl) carbonium cation.

  Specific examples of the ammonium cation include trialkylammonium cations such as trimethylammonium cation, triethylammonium cation, tri (n-propyl) ammonium cation, and tri (n-butyl) ammonium cation; N, N-dimethylanilinium cation, N, N-diethylanilinium cation, N, N-diphenylanilinium cation such as N, N, 2,4,6-pentamethylanilinium cation; dialkylammonium cation such as di (isopropyl) ammonium cation and dicyclohexylammonium cation Etc.

  Specific examples of the phosphonium cation include triarylphosphonium cations such as triphenylphosphonium cation, tri (methylphenyl) phosphonium cation, and tri (dimethylphenyl) phosphonium cation.

R ¹⁷⁺ is preferably a carbonium cation, an ammonium cation or the like, and particularly preferably a triphenylcarbonium cation, an N, N-dimethylanilinium cation or an N, N-diethylanilinium cation.

  Examples of the ionic compound include trialkyl-substituted ammonium salts, N, N-dialkylanilinium salts, dialkylammonium salts, and triarylphosphonium salts.

  Specific examples of the trialkyl-substituted ammonium salt include triethylammonium tetraphenylborate, tri (n-propyl) ammonium tetraphenylborate, tri (n-butyl) ammonium tetraphenylborate, trimethylammonium tetra (p-tolyl) borate, Trimethylammonium tetra (o-tolyl) borate, tri (n-butyl) ammonium tetra (pentafluorophenyl) borate, tri (n-propyl) ammonium tetra (o, p-dimethylphenyl) borate, tri (n-butyl) ammonium Tetra (m, m-dimethylphenyl) borate, tri (n-butyl) ammonium tetra (p-trifluoromethylphenyl) borate, tri (n-butyl) ammonium tetra (3,5-di Trifluoromethyl phenyl) borate, tri (n- butyl) ammonium tetra (o-tolyl) borate.

  Specific examples of the N, N-dialkylanilinium salt include, for example, N, N-dimethylanilinium tetraphenylborate, N, N-diethylanilinium tetraphenylborate, N, N, 2,4,6-pentamethylaniline. Examples thereof include nium tetraphenylborate.

  Specific examples of the dialkylammonium salt include di (n-propyl) ammonium tetra (pentafluorophenyl) borate and dicyclohexylammonium tetraphenylborate.

  Further, as ionic compounds, triphenylcarbenium tetrakis (pentafluorophenyl) borate, N, N-dimethylanilinium tetrakis (pentafluorophenyl) borate, ferrocenium tetra (pentafluorophenyl) borate, triphenylcarbenium pentaphenyl Examples thereof include cyclopentadienyl complexes, N, N-diethylanilinium pentaphenylcyclopentadienyl complexes, and boron compounds represented by the following formula (IV) or (V).

（式中、Ｅｔはエチル基を示す。）

(In the formula, Et represents an ethyl group.)

ボラン化合物として具体的には、たとえばデカボラン（１４）； ビス〔トリ（ｎ−ブチル）アンモニウム〕ノナボレート、ビス〔トリ（ｎ−ブチル）アンモニウム〕デカボレート、ビス〔トリ（ｎ−ブチル）アンモニウム〕ウンデカボレート、ビス〔トリ（ｎ−ブチル）アンモニウム〕ドデカボレート、ビス〔トリ（ｎ−ブチル）アンモニウム〕デカクロロデカボレート、ビス〔トリ（ｎ−ブチル）アンモニウム〕ドデカクロロドデカボレートなどのアニオンの塩； トリ（ｎ−ブチル）アンモニウムビス（ドデカハイドライドドデカボレート）コバルト酸塩（ＩＩＩ）、ビス〔トリ（ｎ−ブチル）アンモニウム〕ビス（ドデカハイドライドドデカボレート）ニッケル酸塩（ＩＩＩ）などの金属ボランアニオンの塩などが挙げられる。

Specific examples of the borane compound include decaborane (14); bis [tri (n-butyl) ammonium] nonaborate, bis [tri (n-butyl) ammonium] decaborate, bis [tri (n-butyl) ammonium] undeca. Salts of anions such as borate, bis [tri (n-butyl) ammonium] dodecaborate, bis [tri (n-butyl) ammonium] decachlorodecaborate, bis [tri (n-butyl) ammonium] dodecachlorododecaborate; Of metal borane anions such as tri (n-butyl) ammonium bis (dodecahydridododecaborate) cobaltate (III), bis [tri (n-butyl) ammonium] bis (dodecahydridododecaborate) nickate (III) Examples include salt.

  Specific examples of the carborane compound include 4-carbanonaborane (14), 1,3-dicarbanonaborane (13), 6,9-dicarbadecarborane (14), dodecahydride-1-phenyl-1, 3-dicarbanonaborane, dodecahydride-1-methyl-1,3-dicarbanonaborane, undecahydride-1,3-dimethyl-1,3-dicarbanonaborane, 7,8-dicarbaundecaborane (13), 2,7-dicarbaound decaborane (13), undecahydride-7,8-dimethyl-7,8-dicarbaound decaborane, dodecahydride-11-methyl-2,7-dicarbound decaborane , Tri (n-butyl) ammonium 1-carbadecaborate, tri (n-butyl) ammonium 1-carbaundecaborate, Li (n-butyl) ammonium 1-carbadodecaborate, tri (n-butyl) ammonium 1-trimethylsilyl-1-carbadeborate, tri (n-butyl) ammonium bromo-1-carbadodecaborate, tri (n-butyl) ) Ammonium 6-carbadecaborate (14), tri (n-butyl) ammonium 6-carbadecaborate (12), tri (n-butyl) ammonium 7carbaundecaborate (13), tri (n-butyl) ammonium 7,8-dicarbaound decaborate (12), tri (n-butyl) ammonium 2,9-dicarbaound decaborate (12), tri (n-butyl) ammonium dodecahydride-8-methyl-7,9-dicar Bound deborate, tri (n-butyl) ammonium undecahydrate Ride-8-ethyl-7,9-dicarbaundecaborate, tri (n-butyl) ammonium undecahydride-8-butyl-7,9-dicarbaundecaborate, tri (n-butyl) ammonium undecahydride 8-allyl-7,9-dicarbaundecaborate, tri (n-butyl) ammonium undecahydride-9-trimethylsilyl-7,8-dicarbaundecaborate, tri (n-butyl) ammonium undecahydride-4, Salts of anions such as 6-dibromo-7-carbaundecaborate; tri (n-butyl) ammonium bis (nonahydride-1,3-dicarbanonaborate) cobaltate (III), tri (n-butyl) Ammonium bis (undecahydride-7,8-dicarboundeca Rate) ferrate (III), tri (n-butyl) ammonium bis (undecahydride-7,8-dicarbaundecaborate) cobaltate (III), tri (n-butyl) ammonium bis (undecahydride) -7,8-dicarbaundecaborate) nickelate (III), tri (n-butyl) ammonium bis (undecahydride-7,8-dicarbaundecaborate) cuprate (III), tri (n- (Butyl) ammonium bis (undecahydride-7,8-dicarbaundecaborate) aurate (III), tri (n-butyl) ammonium bis (nonahydride-7,8-dimethyl-7,8-dicarbaundeca) Borate) ferrate (III), tri (n-butyl) ammonium bis (nonahydride-7,8-di) Methyl-7,8-dicarbaundecaborate) chromate (III), tri (n-butyl) ammonium bis (tribromooctahydride-7,8-dicarboundeborate) cobaltate (III), tris [ Tri (n-butyl) ammonium] bis (undecahydride-7-carbaundecaborate) chromate (III), bis [tri (n-butyl) ammonium] bis (undecahydride-7-carbaundecaborate ) Manganate (IV), bis [tri (n-butyl) ammonium] bis (undecahydride-7-carbaundecaborate) cobaltate (III), bis [tri (n-butyl) ammonium] bis ( Metal carbonates such as undecahydride-7-carbaundecaborate) nickelate (IV) Such as the salt of borane anion, and the like.

  The heteropoly compound is composed of atoms composed of silicon, phosphorus, titanium, germanium, arsenic or tin and one or more atoms selected from vanadium, niobium, molybdenum and tungsten. Specifically, phosphovanadic acid, germanovanadic acid, arsenic vanadic acid, phosphoniobic acid, germanoniobic acid, siliconomolybdic acid, phosphomolybdic acid, titanium molybdic acid, germanomolybdic acid, arsenic molybdic acid, tin molybdic acid, phosphorus Tungstic acid, germanotungstic acid, tin tungstic acid, phosphomolybdovanadic acid, lintongost vanadic acid, germanotangostovanadic acid, phosphomolybdotangostobanamic acid, germanomolybdo tungstovanadate, phosphomolybdo Tungstic acid, phosphomolybniobic acid, salts of these acids, such as metals of Group 1 or 2 of the periodic table, specifically lithium, sodium, potassium, rubidium, cesium, beryllium, magnesium, calcium, strontium , With barium etc. Salts, and organic salts such as triphenylethyl salt, and isopoly compound can be used but not limited thereto.

The heteropoly compound and the isopoly compound are not limited to one of the above compounds, and two or more of them can be used.
The above (b-3) ionized ionic compounds are used singly or in combination of two or more.

When the olefin multimerization catalyst of the present invention is used, an olefin multimer can be obtained with high activity, and particularly when ethylene is used as the olefin, the selectivity of 1-hexene is high.
For example, when an organoaluminum oxy compound (b-2) such as methylaluminoxane is used in combination as a promoter component, 1-hexene can be produced by showing very high trimerization activity with respect to ethylene. Even if an ionized ionic compound (b-3) such as triphenylcarbonium tetrakis (pentafluorophenyl) borate is used as a promoter component, 1-hexene can be obtained from ethylene with good activity and very high selectivity. .

  The olefin multimerization catalyst according to the present invention includes (A) a transition metal complex compound, and if necessary, (B) (b-1) an organometallic compound, (b-2) an organoaluminum oxy compound, and (B-3) It contains at least one compound selected from ionized ionic compounds, and may further contain (C) a carrier as described later, if necessary.

[(C) Carrier]
The carrier (C) used as necessary in the present invention is an inorganic or organic compound and is a granular or fine particle solid. In the present invention, the (C) carrier is a carrier for carrying the (A) and / or (B). Among these, as the inorganic compound, a porous oxide, an inorganic halide, clay, clay mineral, or an ion-exchange layered compound is preferable.

As the porous oxide, specifically, SiO ₂ , Al ₂ O ₃ , MgO, ZrO, TiO ₂ , B ₂ O ₃ , CaO, ZnO, BaO, ThO ₂ or the like, or a composite or mixture containing these is used. For example, natural or synthetic zeolite, SiO ₂ —MgO, SiO ₂ —Al ₂ O ₃ , SiO ₂ —TiO ₂ , SiO ₂ —V ₂ O ₅ , SiO ₂ —Cr ₂ O ₃ , SiO ₂ —TiO ₂ —MgO, etc. Can be used. Of these, those containing SiO ₂ and / or Al ₂ O ₃ as main components are preferred.

Note that the inorganic oxide includes a small amount of Na ₂ CO ₃ , K ₂ CO ₃ , CaCO ₃ , MgCO ₃ , Na ₂ SO ₄ , Al ₂ (SO ₄ ) ₃ , BaSO ₄ , KNO ₃ , Mg (NO ₃ ). ₂ , Al (NO ₃ ) ₃ , Na ₂ O, K ₂ O, Li ₂ O and other carbonates, sulfates, nitrates, and oxide components may be contained.

Such porous oxides have different properties depending on the type and production method, but the carrier preferably used in the present invention has a particle size of 0.5 to 300 μm and a specific surface area of 50 to 1000 m ² / g. It is desirable that the pore volume be in the range of 0.3 to 3.0 cm ³ / g. Such a carrier is used after being calcined at 100 to 1000 ° C. as necessary.

As the inorganic halide, MgCl ₂ , MgBr ₂ , MnCl ₂ , MnBr ₂ or the like is used. The inorganic halide may be used as it is or after being pulverized by a ball mill or a vibration mill. Further, it is also possible to use a material in which an inorganic halide is dissolved in a solvent such as alcohol and then precipitated into fine particles with a precipitating agent.

  The clay used as a carrier in the present invention is usually composed mainly of a clay mineral. Further, the ion-exchangeable layered compound used as a carrier in the present invention is a compound having a crystal structure in which the surfaces constituted by ionic bonds and the like are stacked in parallel with a weak binding force, and the ions contained can be exchanged It is. Most clay minerals are ion-exchangeable layered compounds. In addition, these clays, clay minerals, and ion-exchange layered compounds are not limited to natural products, and artificial synthetic products can also be used.

Further, as clay, clay mineral or ion-exchangeable layered compound, clay, clay mineral, ionic crystalline compound having a layered crystal structure such as hexagonal fine packing type, antimony type, CdCl ₂ type, CdI ₂ type, etc. It can be illustrated.

Examples of such clays and clay minerals include kaolin, bentonite, kibushi clay, gyrome clay, allophane, hysinger gel, pyrophyllite, ummo group, montmorillonite group, vermiculite, ryokdeite group, palygorskite, kaolinite, nacrite, dickite And halloysite, and the ion-exchangeable layered compounds include α-Zr (HAsO ₄ ) ₂ .H ₂ O, α-Zr (KPO ₄ ) ₂ .3H ₂ O, α-Ti (HPO ₄ ) ₂ , α-Ti (HAsO ₄ ) ₂ .H ₂ O, α-Sn (HPO ₄ ) ₂ .H ₂ O, γ-Zr (HPO ₄ ) ₂ , γ-Ti (HPO ₄ ) ₂ , γ-Ti (NH ₄ Examples thereof include crystalline acidic salts of polyvalent metals such as PO ₄ ) ₂ .H ₂ O.

Such a clay, clay mineral or ion-exchange layered compound preferably has a pore volume of not less than 0.1 cc / g and not less than 0.3 cc / g, as measured by mercury porosimetry. Is particularly preferred. Here, the pore volume is measured in a pore radius range of 20 to ³ × 10 ⁴ angstroms by mercury porosimetry using a mercury porosimeter. When a carrier having a pore volume with a radius of 20 angstroms or more and smaller than 0.1 cc / g is used as a carrier, high multimerization activity tends to be difficult to obtain.

  The clay and clay mineral used in the present invention are preferably subjected to chemical treatment. As the chemical treatment, any of a surface treatment that removes impurities adhering to the surface and a treatment that affects the crystal structure of clay can be used. Specific examples of the chemical treatment include acid treatment, alkali treatment, salt treatment, and organic matter treatment. In addition to removing impurities on the surface, the acid treatment increases the surface area by eluting cations such as Al, Fe, and Mg in the crystal structure. Alkali treatment destroys the crystal structure of the clay, resulting in a change in the structure of the clay. In the salt treatment and the organic matter treatment, an ion complex, a molecular complex, an organic derivative, and the like can be formed, and the surface area and interlayer distance can be changed.

The ion-exchangeable layered compound used in the present invention may be a layered compound in a state where the layers are expanded by exchanging the exchangeable ions between the layers with other large and bulky ions using the ion-exchange property. . Such bulky ions play a role of supporting pillars to support the layered structure and are usually called pillars. Moreover, introducing another substance between the layers of the layered compound in this way is called intercalation. Examples of guest compounds to be intercalated include cationic inorganic compounds such as TiCl ₄ and ZrCl ₄ , metal alkoxides such as Ti (OR) ₄ , Zr (OR) ₄ , PO (OR) ₃ , and B (OR) ₃ ( R is a hydrocarbon group), metal hydroxide ions such as [Al ₁₃ O ₄ (OH) ₂₄ ] ⁷⁺ , [Zr ₄ (OH) ₁₄ ] ²⁺ , [Fe ₃ O (OCOCH ₃ ) ₆ ] ⁺ Etc.

These compounds are used alone or in combination of two or more.
Further, when these compounds were intercalated, they were obtained by hydrolyzing metal alkoxides such as Si (OR) ₄ , Al (OR) ₃ , Ge (OR) ₄ (R is a hydrocarbon group, etc.). A dimerized product, a colloidal inorganic compound such as SiO _2, and the like can also coexist. Examples of the pillar include oxides generated by heat dehydration after intercalation of the metal hydroxide ions between layers.

  The clay, clay mineral, and ion-exchangeable layered compound used in the present invention may be used as they are, or may be used after a treatment such as ball milling or sieving. Further, it may be used after newly adsorbing and adsorbing water or after heat dehydration treatment. Furthermore, you may use individually or in combination of 2 or more types.

Among these, preferred are clays or clay minerals, and particularly preferred are montmorillonite, vermiculite, hectorite, teniolite and synthetic mica.
Examples of the organic compound include granular or fine particle solids having a particle size in the range of 10 to 300 μm. Specifically, a (co) dimer or vinylcyclohexane produced mainly from an α-olefin having 2 to 14 carbon atoms such as ethylene, propylene, 1-butene and 4-methyl-1-pentene, Examples thereof include (co) dimers produced with styrene as a main component, and modified products thereof.

  The olefin multimerization catalyst according to the present invention includes the (A) transition metal complex compound, and if necessary, the (B) (b-1) organometallic compound, (b-2) the organoaluminum oxy compound, and (B-3) includes at least one compound selected from ionized ionic compounds, and further includes a carrier (C) as necessary, and further includes (D) an organic compound component as described later as necessary. You can also.

[(D) Organic compound component]
In the present invention, the organic compound component (D) is used for the purpose of improving the multimerization performance, if necessary. Examples of such organic compounds include, but are not limited to, alcohols, phenolic compounds, carboxylic acids, phosphorus compounds, and sulfonates.

As alcohols and phenolic compounds, those represented by R ²² —OH are usually used (where R ²² is a hydrocarbon group having 1 to 50 carbon atoms or a halogenated group having 1 to 50 carbon atoms). As the alcohol, R ²² is preferably a halogenated hydrocarbon.

Moreover, as a phenolic compound, what substituted the (alpha) and (alpha) '-position of the hydroxyl group with the C1-C20 hydrocarbon is preferable.
As the carboxylic acid, one represented by R ²³ —COOH is usually used. R ²³ represents a hydrocarbon group having 1 to 50 carbon atoms or a halogenated hydrocarbon group having 1 to 50 carbon atoms, and a halogenated hydrocarbon group having 1 to 50 carbon atoms is particularly preferable.

As the phosphorus compound, phosphoric acid having P—O—H bond, P—OR, phosphate having P═O bond, and phosphine oxide compound are preferably used.
As the sulfonate, those represented by the following general formula (VI) are used.

式（ＶＩ）中、Ｍ⁴は周期律表第１〜１４族の原子である。Ｒ²⁴は水素、炭素原子数１〜２０の炭化水素基または炭素原子数１〜２０のハロゲン化炭化水素基である。Ｘは水素原子、ハロゲン原子、炭素原子数が１〜２０の炭化水素基、炭素原子数が１〜２０のハロゲン化炭化水素基である。ｍは１〜７の整数であり、ｎはＭの価数であり、１≦ｎ≦７である。

In formula (VI), M ⁴ is an atom of Groups 1-14 of the periodic table. R ²⁴ is hydrogen, a hydrocarbon group having 1 to 20 carbon atoms, or a halogenated hydrocarbon group having 1 to 20 carbon atoms. X is a hydrogen atom, a halogen atom, a hydrocarbon group having 1 to 20 carbon atoms, or a halogenated hydrocarbon group having 1 to 20 carbon atoms. m is an integer of 1 to 7, n is the valence of M, and 1 ≦ n ≦ 7.

  The olefin multimerization catalyst of the present invention can be used for olefin multimerization. Examples of olefins include ethylene, propylene, 1-butene, 1-pentene, 1-hexene, 4-methyl-1-pentene, vinylcyclohexene, vinyl compounds such as styrene, 1-octene, 1-decene, 2-butene, cyclopentene, Preferred examples include internal olefins such as cyclohexene and norbornene, with ethylene being particularly preferred. A plurality of the olefins described above may be co-multiplied.

  Hereinafter, a method for producing an olefin multimer in which an olefin multimerization reaction is performed in the presence of the olefin multimerization catalyst will be described.

[Olefin multimer production method]
A method for producing the olefin multimer will be described.
In the method for producing an olefin multimer according to the present invention, an olefin multimerization reaction, preferably a trimerization reaction or a tetramerization is performed in the presence of the olefin multimerization catalyst.
An ethylene multimerization reaction using ethylene as an olefin is preferable, and a method of producing 1-hexene by an ethylene trimerization reaction and a method of producing 1-octene by an ethylene tetramerization reaction are particularly preferable.

  In the multimerization reaction, the method of adding the transition metal complex compound (A) (hereinafter simply referred to as “component (A)”) to the reactor, the method of using each component, the method of addition, and the order of addition are arbitrarily selected. The following method is exemplified.

  (1) Component (A) and at least one component (B) selected from (b-1) an organometallic compound, (b-2) an organoaluminum oxy compound, and (b-3) an ionized ionic compound (below) And simply adding “component (B)” to the reactor in any order.

(2) A method in which a catalyst in which the component (A) and the component (B) are contacted in advance is added to the reactor.
(3) A method in which the catalyst component in which the component (A) and the component (B) are contacted in advance, and the component (B) are added to the reactor in an arbitrary order. In this case, the component (B) may be the same or different.

(4) A method in which the catalyst component having component (A) supported on carrier (C) and component (B) are added to the reactor in any order.
(5) A method in which a catalyst in which component (A) and component (B) are supported on a carrier (C) is added to a reactor.

  (6) A method in which the catalyst component in which the component (A) and the component (B) are supported on the carrier (C), and the component (B) are added to the reactor in an arbitrary order. In this case, the component (B) may be the same or different.

(7) A method in which the catalyst component having component (B) supported on support (C) and component (A) are added to the reactor in any order.
(8) A method in which the catalyst component having component (B) supported on carrier (C), component (A), and component (B) are added to the reactor in any order. In this case, the component (B) may be the same or different.

(9) A method in which a component carrying component (A) on carrier (C) and a component carrying component (B) on carrier (C) are added to the reactor in any order.
(10) A method in which component (A) is supported on carrier (C), component (B) is supported on carrier (C), and component (B) is added to the reactor in any order. In this case, the component (B) may be the same or different.

(11) A method in which component (A), component (B), and component (D) are added to the reactor in any order.
(12) A method in which component (B) and component (D) are contacted in advance, and component (A) are added to the reactor in any order.

(13) A method in which the component (B) and the component (D) supported on the carrier (C) and the component (A) are added to the reactor in any order.
(14) A method in which the catalyst component obtained by previously contacting the component (A) and the component (B), and the component (D) are added to the reactor in an arbitrary order.

  (15) A method in which the catalyst component in which the component (A) and the component (B) are previously contacted, and the component (B) and the component (D) are added to the reactor in an arbitrary order. In this case, the component (B) may be the same or different.

  (16) A method in which a catalyst component in which the component (A) and the component (B) are previously contacted and a component in which the component (B) and the component (D) are previously contacted are added to the reactor in an arbitrary order. In this case, the component (B) may be the same or different.

(17) A method in which the component (A) supported on the carrier (C), the component (B), and the component (D) are added to the reactor in any order.
(18) A method in which a component having component (A) supported on carrier (C) and a component in which component (B) and component (D) are contacted in advance are added to the reactor in any order.

(19) A method in which a catalyst obtained by bringing the component (A), the component (B), and the component (D) into contact in advance in an arbitrary order is added to the reactor.
(20) A method in which the catalyst component obtained by bringing the component (A), the component (B) and the component (D) into contact in advance in an arbitrary order and the component (B) are added to the reactor in an arbitrary order. In this case, the component (B) may be the same or different.

(21) A method in which a catalyst having components (A), (B) and (D) supported on a carrier (C) is added to a reactor.
(22) A method in which component (A), component (B) and component (D) are supported on a carrier (C) and a catalyst component and component (B) are added to the reactor in any order. In this case, the component (B) may be the same or different.

  In the method for producing an olefin multimer according to the present invention, the olefin multimer is obtained by multimerizing the olefin in the presence of the olefin multimerization catalyst as described above. In the present invention, multimerization can be carried out by any of liquid phase reaction methods such as dissolution reaction and suspension reaction, or gas phase reaction methods.

  In the liquid phase reaction method, an inert hydrocarbon medium is used. Specific examples of the inert hydrocarbon medium used include propane, butane, isobutane, pentane, isopentane, hexane, heptane, octane, decane, dodecane, Aliphatic hydrocarbons such as kerosene; Alicyclic hydrocarbons such as cyclopentane, cyclohexane, and methylcyclopentane; Aromatic hydrocarbons such as benzene, toluene, xylene, trimethylbenzene, and tetralin; Ethylene chloride, chlorobenzene, and dichloromethane And halogenated hydrocarbons or a mixture thereof. As the reaction solvent, pentane, n-hexane and n-heptane are particularly preferable.

Using the olefin multimerization catalyst as described above, olefin multimer is produced by multimerizing olefin, preferably 1-hexene is produced by trimerization of ethylene or 1-octene is produced by tetramerization of ethylene. When carried out, component (A) is usually used in an amount of 10 ⁻¹² to 10 ⁻² mol, preferably 10 ⁻¹⁰ to 10 ⁻³ mol, per liter of reaction volume. In the present invention, an olefin multimer can be obtained with high multimerization activity even when component (A) is used at a relatively low concentration.

  Moreover, when using a component (B), a component (b-1) is a molar ratio [(b-1) / M of a component (b-1) and the transition metal atom (M) in a component (A). ] Is usually used in an amount of 0.01 to 100,000, preferably 0.05 to 50,000.

  Component (b-2) has a molar ratio [(b-2) / M] of the aluminum atom in component (b-2) and the transition metal atom (M) in component (A) usually 10 to 10. The amount used is 500,000, preferably 20 to 100,000.

Component (b-3) has a molar ratio [(b-3) / M] of component (b-3) to transition metal atom (M) in component (A) usually from 1 to 10, preferably It is used in such an amount as to be 1-5.
In the component (C), the ratio (g / mol) of the mass (g) of the component (C) to the moles of the transition metal atom (M) in the component (A) is usually 100 to 10,000, preferably 1000 to 5000. Is used in such an amount.

  When component (D) is component (b-1) with respect to component (B), the molar ratio [(D) / (b-1)] is usually 0.01 to 10, preferably 0.1 to 0.1. In the case of component (b-2), the molar ratio [(D) / (b-2)] between component (D) and aluminum atom in component (b-2) is usually 0. 0.001 to 2, preferably 0.005 to 1 and in the case of component (b-3), the molar ratio [(D) / (b-3)] is usually 0.01 to 10, preferably Is used in an amount of 0.1-5.

  The reaction temperature of olefin multimerization using such an olefin multimerization catalyst is usually in the range of −50 to 200 ° C., preferably 0 to 170 ° C. The reaction pressure is usually from normal pressure to 10 MPa, preferably from normal pressure to 5 MPa, and the multimerization reaction can be carried out by any of batch, semi-continuous and continuous methods.

  The reaction of olefin multimerization using such an olefin multimerization catalyst may be carried out by adding an antistatic agent. Antistatic agents include polypropylene glycol, polypropylene glycol distearate, ethylenediamine-PEG-PPG-block copolymer, stearyl diethanolamine, lauryl diethanolamine, alkyl diethanolamide, polyoxyalkylene (eg, polyethylene glycol / polypropylene glycol / polyethylene glycol block copolymer) (PEG-PPG-PEG)) and the like are preferable, and polyoxyalkylene (PEG-PPG-PEG) is particularly preferable. These antistatic agents are used in such an amount that the ratio (g / mol) of mass (g) to mol of transition metal atom (M) in component (A) is usually 100 to 10,000, preferably 100 to 1,000. Used.

  The reaction of olefin multimerization using such an olefin multimerization catalyst may be performed by adding hydrogen. The hydrogen pressure in the reaction is 0.01 MPa to 5 MPa, preferably 0.01 MPa to 1 MPa.

EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not limited to these Examples.
The yield of the reaction product and the selectivity of 1-hexene (decenes) were analyzed using gas chromatography (Shimadzu GC-14A, J & W Scientific DB-5 column).

[Catalytic activity]
The mass of the reaction product obtained per unit time was obtained by dividing the mass of the transition metal atom (mmol) in the transition metal catalyst component used for the multimerization.

[Selectivity of 1-hexene (decenes)]
The selectivity of 1-hexene (decenes) was determined according to the following formula.
S (%) = Wp / Wr × 100
S (%): 1-hexene selectivity (weight fraction)
Wr (weight): total weight of products having 4 or more carbon atoms produced by the reaction Wp (weight): weight of 1-hexene produced by the reaction Note that the selectivity for decenes is determined according to the above method. It was.

  In the following, specific examples of synthesis of the transition metal compound (A) of the present invention are shown, and specific examples and comparative examples of ethylene multimerization are shown.

[Synthesis Example 1]
(Synthesis of Compound 3)

充分に乾燥した２００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２‐ｍｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄ（和光純薬工業株式会社製）を３．１９ｇ（２１ｍｍｏｌ）、２−ｂｒｏｍｏ−４，６−ｄｉｆｌｕｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を４．１６ｇ（２０ｍｍｏｌ）、酢酸パラジウム（和光純薬工業株式会社製）を０．０２２ｇ（０．１ｍｍｏｌ）、２‐Ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌ（シグマ アルドリッチ ジャパン 株式会社製）を０．０８２ｇ（０．２ｍｍｏｌ）、リン酸カリウム一水和物（和光純薬工業株式会社製）１３．８ｇ（６０ｍｍｏｌ）加え、トルエン（関東化学株式会社製）４０ｍＬに縣濁させ、１００℃で３時間反応させた。この反応液に水１００ｍＬを加え、トルエンで抽出後、有機層をＭｇＳＯ₄（関東化学株式会社製）で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ （溶離液；ヘキサン（関東化学株式会社製）／酢酸エチル（関東化学株式会社製）＝１９／１）を用いて精製することにより化合物１を２．６８ｇ（５７％、薄黄色液体）を得た。

2.19 g (21 mmol) of 2-methoxyphenylboronic acid (manufactured by Wako Pure Chemical Industries, Ltd.), 2-bromo-4,6-, in a well-dried 200 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer) difluoroline (manufactured by Tokyo Chemical Industry Co., Ltd.) 4.16 g (20 mmol), palladium acetate (manufactured by Wako Pure Chemical Industries, Ltd.) 0.022 g (0.1 mmol), 2-Dicyclohexylphosphino-2 ′, 6′-dimethylbiphenyl ( 0.082 g (0.2 mmol) of Sigma Aldrich Japan Co., Ltd., 13.8 g (60 mmol) of potassium phosphate monohydrate (manufactured by Wako Pure Chemical Industries, Ltd.), and 40 mL of toluene (manufactured by Kanto Chemical Co., Ltd.) It was suspended, and reacted for 3 hours at 100 ° C.. 100 mL of water was added to this reaction liquid, extracted with toluene, the organic layer was dried over MgSO ₄ (manufactured by Kanto Chemical Co., Inc.), and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane (Kanto Chemical Co., Ltd.) / Ethyl acetate (Kanto Chemical Co., Ltd.) = 19/1) to obtain 2.68 g (57 %, Pale yellow liquid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.42-7.36 (m, 1H, Ar—H), 7.26-7.22 (m, 1H, Ar—H), 7.08-7. 00 (m, 2H, Ar-H), 6.84-6.76 (m, 1H, Ar-H), 6.72-6.70 (m, 1H, Ar-H), 3.83 (s , 3H, OCH ₃ ), 3.61 (br, 2H, NH ₂ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物１を１．２９ｇ（５．５ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｍｅｔｈｙｌｂｅｎｚａｌｄｅｈｙｄｅ（Ｊｏｕｒｎａｌ ｏｆ Ａｍｅｒｉｃａｎ Ｃｈｅｍｉｃａｌ Ｓｏｃｉｅｔｙ誌２００１年１２３巻６８４７−６８５６頁の記載に従い合成した。）１．３５ｇ（５．０ｍｍｏｌ）、アンバーリスト１５（Ｈ）（和光純薬工業株式会社製）を加えトルエン４０ｍＬ加えた後、還流下で３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノール（関東化学株式会社製）から再結晶することにより化合物２を２．０６ｇ（収率 ８３％、黄色固体）得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 1.29 g (5.5 mmol) of compound 1 and 3-adamantyl-2-hydroxy-5-methylbenzaldehyde (Journal) of American Chemical Society 2001, volume 123, pages 6847-6856.) 1.35 g (5.0 mmol), Amberlyst 15 (H) (manufactured by Wako Pure Chemical Industries, Ltd.) was added and 40 mL of toluene was added. Then, it was made to react under reflux for 3 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol (manufactured by Kanto Chemical Co., Inc.) gave 2.06 g of Compound 2 (yield 83%, yellow). Solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.1 (s, 1H, OH), 8.46 (s, 1H, N═CH), 7.36-7.16 (m, 2H, Ar—H) , 7.05-6.82 (m, 6H, Ar -H), 3.71 (s, 3H, OCH 3), 2.24 (s, 3H, CH 3), 2.08 (s, 9H, adamantyl), 1.76 (s, 6H, adamantyl)

充分に乾燥した５０ｍＬナスフラスコ（三方コック、磁気攪拌子入り）にＴｉＣｌ₄（ｔｈｆ）₂（シグマ アルドリッチ ジャパン 株式会社製）０．６６８ｇ（２．０ｍｍｏｌ）、テトラヒドロフラン（関東化学株式会社製）を１０ｍＬ加え−７８℃に冷却する。この混合液に化合物２を０．９７３ｇ（２．０ｍｍｏｌ）をテトラヒドロフラン２．５ｍＬに溶かし滴下した後、室温まで昇温させつつ１３時間反応させた。この反応液に、ヘキサン１０ｍＬを加え析出させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物３のテトラヒドロフラン錯体を１．１８ｇ（収率 ８３％、オレンジ色固体）得た。

TiCl ₄ (thf) ₂ (Sigma Aldrich Japan Co., Ltd.) 0.668 g (2.0 mmol), tetrahydrofuran (Kanto Chemical Co., Ltd.) Add and cool to -78 ° C. 0.973 g (2.0 mmol) of Compound 2 was dissolved in 2.5 mL of tetrahydrofuran and added dropwise to this mixed solution, and then reacted for 13 hours while raising the temperature to room temperature. To this reaction solution, 10 mL of hexane was added for precipitation. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 1.18 g (yield 83%, orange solid) of the tetrahydrofuran complex of Compound 3.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.07 (d, 1H, J = 2.2 Hz, N = CH), 7.34-7.18 (m, 5H, Ar—H), 7.02- 6.68 (m, 3H, Ar- H), 4.26 (s, 3H, OCH 3), 3.71 (t, 4H, J = 6.5Hz, thf), 2.26 (s, 3H, _{CH 3), 2.12 (bs,} 6H, adamantyl), 2.07 (bs, 3H, adamantyl), 1.85 (d, 3H, J = 12Hz, adamantyl), 1.80-1.76 (m , 4H, thf), 1.71 (d, 3H, J = 12 Hz, adamantyl)

[Synthesis Example 2]
(Synthesis of Compound 6)

充分に乾燥した２００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２‐ｍｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄを３．１９ｇ（２１ｍｍｏｌ）、２−ｂｒｏｍｏ−６−ｆｌｕｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を３．８０ｇ（２０ｍｍｏｌ）、酢酸パラジウムを０．０２２ｇ（０．１ｍｍｏｌ）、２‐Ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌを０．０８２ｇ（０．２ｍｍｏｌ）、リン酸カリウム一水和物１３．８ｇ（６０ｍｍｏｌ）加え、トルエン４０ｍＬに縣濁させ、１００℃で３時間反応させた。この反応液に水１００ｍＬを加え、トルエンで抽出後、有機層をＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９３／７）を用いて精製することにより化合物４を２．７１ｇ（６２％、薄黄色液体）を得た。

In a well-dried 200 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer), 3.19 g (21 mmol) of 2-methoxyphenylboronic acid and 3 of 2-bromo-6-fluoroline (manufactured by Tokyo Chemical Industry Co., Ltd.) .80 g (20 mmol), 0.022 g (0.1 mmol) of palladium acetate, 0.082 g (0.2 mmol) of 2-Diccyclohexylphosphino-2 ′, 6′-dimethylbiphenyl, 13.8 g of potassium phosphate monohydrate ( 60 mmol), suspended in 40 mL of toluene, and reacted at 100 ° C. for 3 hours. 100 mL of water was added to the reaction solution, and extracted with toluene. The organic layer was dried over MgSO ₄ and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 93/7) to obtain 2.71 g (62%, light yellow liquid) of Compound 4.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.40-7.37 (m, 1H, Ar—H), 7.27-7.23 (m, 1H, Ar—H) 7.07-6.89 (m, 4H, Ar-H ), 6.77-6.69 (m, 1H, Ar-H), 3.82 (s, 3H, OCH 3), 3.76 (br, 2H, NH 2)

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物４を１．１４ｇ（５．５ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｍｅｔｈｙｌｂｅｎｚａｌｄｅｈｙｄｅ１．３５ｇ（５．０ｍｍｏｌ）、アンバーリスト１５（Ｈ）を１３５ｍｇ加えトルエン４０ｍＬ加えた後、還流下で３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物５を１．６６ｇ（収率 ７１％、オレンジ固体）得た。

1.14 g (5.5 mmol), 3-adamantyl-2-hydroxy-5-methylbenzaldehyde 1.35 g in a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer) (5.0 mmol) and 135 mg of Amberlyst 15 (H) were added, and 40 mL of toluene was added, followed by reaction for 3 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 1.66 g of Compound 5 (yield 71%, orange solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.2 (s, 1H, OH), 8.48 (s, 1H, N═CH), 7.33-6.83 (m, 9H, Ar—H) , 3.71 (s, 3H, OCH ₃ ), 2.24 (s, 3H, CH ₃ ), 2.10 (s, 9H, adamantyl), 1.77 (s, 6H, adamantyl)

充分に乾燥した５０ｍＬナスフラスコ（三方コック、磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（シグマ アルドリッチ ジャパン 株式会社製）（１．０ｍｍｏｌ／ｍＬ）を２．２ｍＬ（２．２ｍｍｏｌ）、トルエンを１５ｍＬ加え−７８℃に冷却した。この混合液に化合物５を０．９３９ｇ（２．０ｍｍｏｌ）をトルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ２０時間反応させた。この反応液を減圧下で約５ｍＬまで濃縮した後、ヘキサン１０ｍＬを加え析出させ、析出物をろ取し、ヘキサン１０ｍＬで洗浄後、乾燥させることにより、化合物６を０．６４０ｇ（収率 ４８％、赤褐色固体）得た。

A well-dried 50 mL eggplant flask (with three-way cock and magnetic stirrer) was charged with 2.2 mL (2.2 mmol) of toluene solution of TiCl ₄ (manufactured by Sigma Aldrich Japan Co., Ltd.) (1.0 mmol / mL) and 15 mL of toluene. Added and cooled to -78 ° C. In this mixed solution, 0.939 g (2.0 mmol) of Compound 5 was dissolved in 5 mL of toluene and dropped, and then reacted for 20 hours while raising the temperature to room temperature. After concentrating the reaction solution to about 5 mL under reduced pressure, 10 mL of hexane was added for precipitation, and the precipitate was collected by filtration, washed with 10 mL of hexane, and dried to give 0.640 g of Compound 6 (yield 48%). A reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.11 (d, 1H, J = 2.7 Hz, N = CH), 7.46-7.14 (m, 8H, Ar—H), 7.07 ( d, 1H, J = 1.4Hz, Ar-H), 4.39 (s, 3H, OCH 3), 2.32 (s, 3H, CH 3), 2.21 (bs, 6H, adamantyl), 2.16 (bs, 3H, adamantyl), 1.93 (d, 3H, J = 12 Hz, adamantyl), 1.80 (d, 3H, J = 12 Hz, adamantyl)

[Synthesis Example 3]
(Synthesis of Compound 10)

充分に乾燥した３００ｍＬ三口ナスフラスコ（滴下ロート、三方コック付、磁気攪拌子入り）に１‐ｍｅｔｈｏｘｙ‐３，５‐ｄｉｍｅｔｈｙｌｂｅｎｚｅｎｅ（東京化成工業株式会社製）を８．１７ｇ（６０ｍｍｏｌ）、ジエチルエーテル１２０ｍＬを加え、氷浴にて０℃まで冷却した後、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（東京化成工業株式会社製）７．６７ｇ（６６ｍｍｏｌ）を加え、ノルマルブチルリチウムのヘキサン溶液（１．６ｍｏｌ／Ｌ）３９．８ｍＬ（６６ｍｍｏｌ）を滴下した後、５時間反応させた。５００ｍＬ三口ナスフラスコ（三方コック付、磁気攪拌子入り）にジエチルエーテル６０ｍＬ、ホウ酸トリメチル（シグマ アルドリッチ ジャパン 株式会社製）１２．４７ｇ（１２０ｍｍｏｌ）を加えた後、−７８℃に冷却した後に、先ほど調整した反応液を滴下し、そのまま室温まで昇温させつつ１８時間反応させた。この反応液に１０ｗｔ％塩酸水（関東化学株式会社製）１００ｍＬを加えた後、酢酸エチル５０ｍＬ×３で抽出後、有機層を純水５０ｍＬ×２で洗浄し、ＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより、粗生成物を得た。得られた粗生成物をトルエンから再結晶することにより、化合物７を６．６７ｇ（６２％、白色固体）を得た。

8.17 g (60 mmol) of 1-methoxy-3,5-dimethylbenzene (manufactured by Tokyo Chemical Industry Co., Ltd.), 120 mL of diethyl ether in a well-dried 300 mL three-necked eggplant flask (with dropping funnel, with three-way cock, with magnetic stirrer) After cooling to 0 ° C. in an ice bath, 7.67 g (66 mmol) of N, N, N ′, N′-tetramethylethylenediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) is added, and a hexane solution of normal butyl lithium (1.6 mol / L) 39.8 mL (66 mmol) was added dropwise, followed by reaction for 5 hours. After adding 60 mL of diethyl ether and 12.47 g (120 mmol) of trimethyl borate (manufactured by Sigma Aldrich Japan Co., Ltd.) to a 500 mL three-necked eggplant flask (with a three-way cock and containing a magnetic stirrer), the mixture was cooled to −78 ° C. The prepared reaction solution was added dropwise and reacted for 18 hours while raising the temperature to room temperature. After adding 100 mL of 10 wt% hydrochloric acid (manufactured by Kanto Chemical Co., Inc.) to this reaction solution, extraction with 50 mL × 3 ethyl acetate was performed, and then the organic layer was washed with 50 mL × 2 pure water, dried over MgSO ₄ , The crude product was obtained by distilling off under reduced pressure. The obtained crude product was recrystallized from toluene to obtain 6.67 g (62%, white solid) of Compound 7.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 6.97 (s, 1H, Ar—H), 6.58 (s, 1H, Ar—H), 6.29 (s, 2H, B (OH) ₂ ) , 3.86 (s, 3H, OCH ₃ ), 2.53 (s, 3H, CH ₃ ), 2.32 (s, 3H, CH ₃ )

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に化合物７を１．８９ｇ（１０．５ｍｍｏｌ）、２‐ｃｈｌｏｒｏ‐６‐ｆｌｕｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を１．４６ｇ（１０ｍｍｏｌ）、酢酸パラジウムを０．２２ｇ（０．１ｍｍｏｌ）、２‐Ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌを０．０８２ｇ（０．２ｍｍｏｌ）、リン酸カリウム一水和物６．９１ｇ（３０ｍｍｏｌ）加え、トルエン１８ｍＬに縣濁させ、１００℃で１．５時間反応させた。この反応液に水２０ｍＬを加え、トルエンで抽出後、有機層をＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９５／５）を用いて精製することにより化合物８を１．９５３ｇ（８０％、薄黄色液体）を得た。

In a well-dried 100 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer), 1.89 g (10.5 mmol) of compound 7 and 2-chloro-6-fluoroline (manufactured by Tokyo Chemical Industry Co., Ltd.) 1 .46 g (10 mmol), 0.22 g (0.1 mmol) of palladium acetate, 0.082 g (0.2 mmol) of 2-Diccyclohexylphosphino-2 ′, 6′-dimethylbiphenyl, 6.91 g of potassium phosphate monohydrate ( 30 mmol), suspended in 18 mL of toluene, and reacted at 100 ° C. for 1.5 hours. 20 mL of water was added to this reaction liquid, extracted with toluene, the organic layer was dried over MgSO ₄ , and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 95/5) to obtain 1.953 g (80%, light yellow liquid) of Compound 8.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.04-6.90 (m, 1H, Ar—H), 6.77-6.53 (m, 4H, Ar—H), 3.70 (s, 3H, OCH ₃ ), 3.51 (br, 2H, NH ₂ ), 2.37 (s, 3H, CH ₃ ), 2.03 (s, 3H, CH ₃ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物８を０．７７３ｇ（３．１５ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｍｅｔｈｙｌｂｅｎｚａｌｄｅｈｙｄｅ０．８１１ｇ（３．０ｍｍｏｌ）、アンバーリスト１５（Ｈ）を５０ｍｇ加えトルエン２０ｍＬ加えた後、還流下で８時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物９を０．６８９ｇ（収率 ４６％、黄色固体）得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.773 g (3.15 mmol), 3-adamantyl-2-hydroxy-5-methylbenzaldehyde 0.811 g (3.0 mmol) and 50 mg of Amberlyst 15 (H) were added, and 20 mL of toluene was added, followed by reaction for 8 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.689 g of Compound 9 (yield 46%, yellow solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.1 (s, 1H, OH), 8.51 (s, 1H, N═CH), 7.23-7.00 (m, 3H, Ar—H) , 6.82 (s, 1H, Ar -H), 6.68 (s, 1H, Ar-H), 6.58 (s, 1H, Ar-H), 4.28 (s, 3H, OCH 3 ), 2.30 (s, 3H, CH ₃ ), 2.24 (s, 3H, CH ₃ ), 2.21 (s, 3H, CH ₃ ), 2.08 (bs, 6H, adamantyl), 1 .98 (s, 3H, adamantyl), 1.77 (s, 6H, adamantyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を１．１０ｍＬ（０．５５ｍｍｏｌ）、トルエンを２０ｍＬ加え−７８℃に冷却した。この混合液に化合物９を０．４９８ｇ（１．０ｍｍｏｌ）をトルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１６時間反応させた。この反応液を減圧下で約５ｍＬまで濃縮した後、ヘキサン２５ｍＬを加え析出させ、析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物１０を０．５４５ｇ（収率 ８４％、オレンジ色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 1.10 mL (0.55 mmol) of a toluene solution of TiCl ₄ (1.0 mmol / mL) and 20 mL of toluene were added and cooled to −78 ° C. To this mixed solution, 0.498 g (1.0 mmol) of Compound 9 was dissolved in 5 mL of toluene and dropped, and then reacted for 16 hours while raising the temperature to room temperature. After concentrating the reaction solution to about 5 mL under reduced pressure, 25 mL of hexane was added for precipitation, and the precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.545 g of Compound 10 (yield 84%). Orange solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.11 (d, 1H, J = 2.2 Hz, N = CH), 7.43-7.35 (m, 2H, Ar—H), 7.28- 7.21 (m, 2H, Ar-H), 7.09-7.07 (m, 2H, Ar-H), 6.94 (s, 1H, Ar-H), 4.33 (s, 3H) , OCH ₃ ), 2.33 (s, 3H, CH ₃ ), 2.26 (s, 3H, CH ₃ ), 2.19 (bs, 6H, adamantyl), 2.15 (bs, 3H, adamantyl) 2.11 (s, 3H, CH ₃ ), 1.93 (d, 3H, J = 12 Hz, adamantyl), 1.79 (d, 3H, J = 12 Hz, adamantyl)

[Synthesis Example 4]
(Synthesis of Compound 13)

充分に乾燥した２００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２‐ｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄ（シグマ アルドリッチ ジャパン 株式会社製）を１．８３ｇ（１１．０ｍｍｏｌ）、２−ｃｈｌｏｒｏ−６−ｆｌｕｏｒｏａｎｉｌｉｎｅを１．４６ｇ（１０ｍｍｏｌ）、酢酸パラジウムを０．０１１ｇ（０．０５ｍｍｏｌ）、２‐Ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌを０．０４１ｇ（０．１ｍｍｏｌ）、リン酸カリウム一水和物６．９ｇ（３０ｍｍｏｌ）加え、トルエン２０ｍＬに縣濁させ、１００℃で３時間反応させた。この反応液に水５０ｍＬを加え、トルエンで抽出後、有機層をＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ （溶離液；ヘキサン／酢酸エチル＝９６／４）を用いて精製することにより化合物１１を２．３０ｇ（９９％、薄黄色液体）を得た。

2.83 g (11.0 mmol) of 2-ethoxyphenylboronic acid (manufactured by Sigma Aldrich Japan Co., Ltd.), 2-chloro-6-fluoroline in a well-dried 200 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer) 1.46 g (10 mmol), 0.011 g (0.05 mmol) of palladium acetate, 0.041 g (0.1 mmol) of 2-Dicyclohexylphosphino-2 ′, 6′-dimethylbiphenyl, potassium phosphate monohydrate 9 g (30 mmol) was added, suspended in 20 mL of toluene, and reacted at 100 ° C. for 3 hours. 50 mL of water was added to this reaction liquid, extracted with toluene, the organic layer was dried over MgSO ₄ , and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 96/4) to obtain 2.30 g (99%, light yellow liquid) of Compound 11.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.37-7.24 (m, 2H, Ar—H), 7.06-6.89 (m, 4H, Ar—H), 6.76-6. 68 (m, 1H, Ar- H), 4.05 (q, 2H, J = 6.9Hz, OCH 2), 3.83 (br, 2H, NH 2), 1.30 (t, 3H, J = 6.9Hz, CH ₃₎

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物１１を０．７２９ｇ（３．１５ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５‐ｔｅｒｔ−Ｂｕｔｙｌ‐２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを０．９３７ｇ（３．０ｍｍｏｌ）、アンバーリスト１５（Ｈ）を９４ｍｇ加えトルエン４０ｍＬ加えた後、還流下で６時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、ヘキサンから再結晶することにより化合物１２を１．１８ｇ（収率 ７５％、黄色固体）得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.729 g (3.15 mmol) of compound 11 and 3-adamantyl-5-tert-Butyl-2-hydroxybenzaldehyde 0.937 g (3.0 mmol), 94 mg of Amberlyst 15 (H) and 40 mL of toluene were added, and the mixture was reacted for 6 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from hexane gave 1.18 g of Compound 12 (yield 75%, yellow solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.4 (s, 1H, OH), 8.54 (s, 1H, N═CH), 7.31-7.24 (m, 2H, Ar—H) 7.19-7.10 (m, 4H, Ar-H), 7.01-6.85 (m, 3H, Ar-H), 3.97 (q, 2H, J = 6.9 Hz, OCH) ₂ ), 2.17 (s, 6H, adamantyl), 2.11 (s, 3H, adamantyl), 1.77 (s, 6H, adamantyl), 1.27 (s, 9H, C (CCH ₃ ) ₃ ), 1.26 (t, 3H, J = 6.9 Hz, CH ₃ )

充分に乾燥した１００ｍＬシュレンクフラスコ（、磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を１．６５ｍＬ（１．６５ｍｍｏｌ）、トルエン２０ｍＬを加え−７８℃に冷却した。この混合液に化合物１２を０．７８９ｇ（１．５ｍｍｏｌ）をトルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１８時間反応させた。この反応液を減圧下で約５ｍＬまで濃縮した後に、ヘキサン１０ｍＬを加え析出させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物１３を０．９１４ｇ（収率 ９０％、赤紫色固体）得た。

To a sufficiently dried 100 mL Schlenk flask (with a magnetic stirrer), 1.65 mL (1.65 mmol) of a toluene solution of TiCl ₄ (1.0 mmol / mL) and 20 mL of toluene were added and cooled to −78 ° C. In this mixed solution, 0.789 g (1.5 mmol) of Compound 12 was dissolved in 5 mL of toluene and dropped, and then reacted for 18 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 5 mL under reduced pressure, and 10 mL of hexane was added for precipitation. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.914 g of Compound 13 (yield 90%, red purple solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.18 (d, 1H, J = 3.2 Hz, N = CH), 7.64 (d, 1H, J = 2.2 Hz, Ar—H), 7. 43-7.07 (m, 8H, Ar- H), 5.48-5.41 (m, 1H, OCH 2), 4.86-4.79 (m, 1H, OCH 2), 2.28 (Bs, 6H, adamantyl), 2.22 (bs, 3H, adamantyl), 1.94 (d, 3H, J = 12 Hz, adamantyl), 1.79 (d, 3H, J = 12 Hz, adamantyl), 1 .28 (s, 9H, C (CCH ₃ ) ₃ ), 0.99 (t, 3H, J = 7.0 Hz, CH ₃ )

[Synthesis Example 5]
(Synthesis of Compound 16)

充分に乾燥した２００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２‐ｍｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄを３．１９ｇ（２１ｍｍｏｌ）、２−ｂｒｏｍｏ−４−ｆｌｕｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を３．８０ｇ（２０ｍｍｏｌ）、酢酸パラジウムを０．０２２ｇ（０．１ｍｍｏｌ）、２‐Ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌを０．０８２ｇ（０．２ｍｍｏｌ）、リン酸カリウム一水和物１３．８ｇ（６０ｍｍｏｌ）加え、トルエン４０ｍＬに縣濁させ、１００℃で３時間反応させた。この反応液に水１００ｍＬを加え、トルエンで抽出後、有機層をＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９／１）を用いて精製することにより化合物１４を２．８６ｇ（６６％、薄黄色液体）を得た。

In a well-dried 200 mL three-necked eggplant flask (condenser with three-way cock, with magnetic stirrer), 3.19 g (21 mmol) of 2-methoxyphenylboronic acid and 3 of 2-bromo-4-fluoroaniline (manufactured by Tokyo Chemical Industry Co., Ltd.) .80 g (20 mmol), 0.022 g (0.1 mmol) of palladium acetate, 0.082 g (0.2 mmol) of 2-Diccyclohexylphosphino-2 ′, 6′-dimethylbiphenyl, 13.8 g of potassium phosphate monohydrate ( 60 mmol), suspended in 40 mL of toluene, and reacted at 100 ° C. for 3 hours. 100 mL of water was added to the reaction solution, and extracted with toluene. The organic layer was dried over MgSO ₄ and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 9/1) to obtain 2.86 g (66%, light yellow liquid) of Compound 14.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.37 (t, J = 7.3 Hz, 1H, Ar—H), 7.24 (d, J = 6.2 Hz, 1H, Ar—H), 7. 07-7.02 (m, 2H, Ar-H), 699-6.82 (m, 2H, Ar-H), 6.72-6.67 (m, 1H, Ar-H), 3 .79 (s, 3H, OCH ₃ ), 3.55 (br, 2H, NH ₂ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物１４を１．１４ｇ（５．５ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｍｅｔｈｙｌｂｅｎｚａｌｄｅｈｙｄｅを１．３５ｇ（５．０ｍｍｏｌ）、アンバーリスト１５（Ｈ）を１３５ｍｇ加えトルエン４０ｍＬ加えた後、還流下で３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物１５を１．２８ｇ（収率 ５５％、オレンジ固体）得た。

Into a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, magnetic stirrer) 1.14 g (5.5 mmol) of compound 14 and 1-adamantyl-2-hydroxy-5-methylbenzaldehyde 1 .35 g (5.0 mmol) and 135 mg of Amberlyst 15 (H) were added, and 40 mL of toluene was added, followed by reaction under reflux for 3 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 1.28 g (yield 55%, orange solid) of Compound 15.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.3 (s, 1H, OH), 8.42 (s, 1H, N═CH), 7.37-7.31 (m, 1H, Ar—H) , 7.21-6.92 (m, 8H, Ar -H), 3.74 (s, 3H, OCH 3), 2.26 (s, 3H, CH 3), 2.08 (s, 9H, adamantyl), 1.78 (s, 6H, adamantyl)

充分に乾燥した５０ｍＬナスフラスコ（三方コック、磁気攪拌子入り）にＴｉＣｌ₄（ｔｈｆ）₂０．５００ｇ（１．５ｍｍｏｌ）、テトラヒドロフランを７．５ｍＬ加え−７８℃に冷却した。この混合液に化合物１５を０．６７７ｇ（１．５ｍｍｏｌ）をテトラヒドロフラン１．３ｍＬに溶かし滴下した後、室温まで昇温させつつ１６時間反応させた。この反応液にヘキサン１０ｍＬを加え析出させた後、析出物をろ取し、ヘキサン１０ｍＬで洗浄後、乾燥させることにより、化合物１６のテトラヒドロフラン錯体を０．８４５ｇ（収率 ８１％、オレンジ色固体）得た。

TiCl ₄ (thf) ₂ 0.500 g (1.5 mmol) and 7.5 mL of tetrahydrofuran were added to a well-dried 50 mL eggplant flask (with a three-way cock and a magnetic stirrer), and cooled to −78 ° C. In this mixed solution, 0.677 g (1.5 mmol) of Compound 15 was dissolved in 1.3 mL of tetrahydrofuran and dropped, and then reacted for 16 hours while raising the temperature to room temperature. After 10 mL of hexane was added to the reaction solution to precipitate, the precipitate was collected by filtration, washed with 10 mL of hexane, and dried to obtain 0.845 g of Compound 16 tetrahydrofuran complex (yield 81%, orange solid). Obtained.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.10 (s, 1H, N═CH), 7.41-7.37 (m, 3H, Ar—H), 7.27-7.04 (m, 6H, Ar-H), 4.41 (s, 3H, OCH 3), 3.76 (t, 4H, J = 6.5Hz, thf), 2.33 (s, 3H, CH 3), 2. 19 (bs, 6H, adamantyl), 2.15 (bs, 3H, adamantyl), 1.92 (d, 3H, J = 12 Hz, adamantyl), 1.87-1.82 (m, 4H, thf), 1.79 (d, 3H, J = 12 Hz, adamantyl)

[Synthesis Example 6]
(Synthesis of Compound 19)

充分に乾燥した２００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２‐ｍｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄを１．５２ｇ（１０．０ｍｍｏｌ）、２，６−ｄｉｃｈｌｏｒｏａｎｉｌｉｎｅを３．２０ｇ（２０ｍｍｏｌ）、酢酸パラジウムを０．０１１ｇ（０．０５ｍｍｏｌ）、２‐ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌを０．０４１ｇ（０．１ｍｍｏｌ）、リン酸カリウム一水和物６．９ｇ（３０ｍｍｏｌ）加え、トルエン４０ｍLに縣濁させ、１００℃で３時間反応させた。この反応液に水５０ｍLを加え、トルエンで抽出後、有機層をＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９８／２)を用いて精製することにより化合物１７を１．６５ｇ（７１％、薄黄色液体）を得た。

In a well-dried 200 mL three-necked eggplant flask (condenser with three-way cock, with magnetic stirrer), 1.52 g (10.0 mmol) of 2-methoxyphenylboronic acid, 3.20 g (20 mmol) of 2,6-dichloroaniline, palladium acetate 0.011 g (0.05 mmol), 2-dicyclohexylphosphino-2 ', 6'-dimethylbiphenyl 0.041 g (0.1 mmol), potassium phosphate monohydrate 6.9 g (30 mmol) was added to 40 mL of toluene. It was made turbid and reacted at 100 ° C. for 3 hours. 50 mL of water was added to the reaction solution, extracted with toluene, the organic layer was dried over MgSO ₄ , and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 98/2) to obtain 1.65 g (71%, light yellow liquid) of Compound 17.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.41-7.34 (m, 1H, Ar—H), 7.28-7.22 (m, 2H, Ar—H), 7.07-6. 99 (m, 3H, Ar—H), 6.73 (d, 1H, J = 8.1 Hz, Ar—H), 4.06 (br, 2H, NH ₂ ), 3.80 (s, 3H, OCH ₃ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物１７を０．９９４ｇ（４．２ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５‐ｍｅｔｈｙｌ‐２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを１．０８ｇ（４．０ｍｍｏｌ）、アンバーリスト１５を１０８ｍｇ加えトルエン２０ｍＬ加えた後、還流下で５時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ(溶離液；ヘキサン／酢酸エチル＝９９／１）を用いて精製することにより化合物１８を１．８６ｇ（９６％、黄色固体）を得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.994 g (4.2 mmol) of compound 17 and 3-adamantyl-5-methyl-2-hydroxydehydride 1 0.08 g (4.0 mmol) and 108 mg of Amberlyst 15 were added, 20 mL of toluene was added, and the mixture was reacted under reflux for 5 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 99/1) to obtain 1.86 g (96%, yellow solid) of Compound 18.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.2 (s, 1H, OH), 8.09 (s, 1H, N═CH), 7.48-7.45 (m, 1H, Ar—H) 7.29-6.94 (m, 6H, Ar-H), 6.79 (d, 1H, J = 7.8 Hz, Ar-H), 6.66 (d, 1H, J = 1.6 Hz) , Ar-H), 3.69 ( s, 3H, OCH 3), 2.12 (s, 3H, CH 3), 2.14 (s, 6H, adamantyl), 2.08 (s, 3H, adamantyl ), 1.79 (s, 6H, adamantyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を１．６５ｍＬ（１．６５ｍｍｏｌ）、トルエン２０ｍＬを加え−７８℃にドライアイス−メタノールバスにて冷却した。この混合液に化合物１８を０．７２９ｇ（１．５ｍｍｏｌ）をトルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１６時間反応させた。この反応液を減圧下で約５ｍＬまで濃縮した後に、ヘキサン１０ｍＬを加え析出させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物１９を０．６３２ｇ（収率 ６６％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), add 1.65 mL (1.65 mmol) of a TiCl ₄ toluene solution (1.0 mmol / mL) and 20 mL of toluene to a dry ice-methanol bath at −78 ° C. And cooled. To this mixed solution, 0.729 g (1.5 mmol) of Compound 18 was dissolved and dropped in 5 mL of toluene, and then reacted for 16 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 5 mL under reduced pressure, and 10 mL of hexane was added for precipitation. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.632 g of Compound 19 (yield 66%, reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.00 (s, 1H, N = CH), 7.60 (dd, J = 6.2 Hz, 1.6 Hz, 1H, Ar—H), 7.43− 7.12 (m, 7H, Ar- H), 7.02 (d, 1H, J = 1.1Hz, Ar-H), 4.30 (s, 3H, OCH 3), 2.30 (s, 3H, CH ₃ ), 2.19 (m, 9H, adamantyl), 1.95 (d, 3H, J = 12 Hz, adamantyl), 1.80 (d, 3H, J = 12 Hz, adamantyl)

[Synthesis Example 7]
(Synthesis of Compound 23)

充分に乾燥した２００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に４−ａｍｉｎｏ−３−ｆｌｕｏｒｏｔｏｌｕｅｎｅを５．００ｇ（４０．０ｍｍｏｌ）、Ｎ,Ｎ−ジメチルホルムアミドを１５０ｍＬ加えた後、水冷しつつＮ−ブロモスクシンイミドを７．１１ｇ（４０．０ｍｍｏｌ）をＮ,Ｎ−ジメチルホルムアミド５０ｍＬに溶解させ滴下し、３時間反応させた。この反応液に水３００ｍLを加え、ヘキサンで抽出後、有機層を純水で洗浄し、ＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９７／３)を用いて精製することにより化合物２０を７．０９ｇ（８７％、白色固体）を得た。

After adding 5.00 g (40.0 mmol) of 4-amino-3-fluorotoluene and 150 mL of N, N-dimethylformamide to a well-dried 200 mL three-necked eggplant flask (with a condenser, a three-way cock, and a magnetic stirrer), While cooling with water, 7.11 g (40.0 mmol) of N-bromosuccinimide was dissolved in 50 mL of N, N-dimethylformamide and added dropwise to react for 3 hours. 300 mL of water was added to the reaction solution, and extracted with hexane. The organic layer was washed with pure water, dried over MgSO ₄ , and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 97/3) to obtain 7.09 g (87%, white solid) of Compound 20.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.02 (s, 1H, Ar—H), 6.77 (d, 1H, J = 11 Hz, Ar—H), 3.95 (br, 2H, NH ₂₎ ), 2.22 (s, 3H, CH ₃ )

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２−ｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄ（東京化成工業株式会社製）を１．７４ｇ（１０．５ｍｍｏｌ）、化合物２０を２．０４ｇ（１０ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．０５８ｇ（０．１ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）３．４７ｇ（１１ｍｍｏｌ）加え、イソプロピルアルコール４０ｍＬに溶解させ、８０℃で６時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９５／５）を用いて精製することにより化合物２１を１．５７ｇ（６４％、無色液体）得た。

2.74 g (10.5 mmol) of 2-ethoxyphenylboronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) and 2.04 g of Compound 20 (100 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer)) 10 mmol), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) -chloride (manufactured by Sigma Aldrich Japan Co., Ltd.), 0.058 g (0.1 mmol), barium hydroxide eight 3.47 g (11 mmol) of a hydrate (manufactured by Wako Pure Chemical Industries, Ltd.) was added, dissolved in 40 mL of isopropyl alcohol, and reacted at 80 ° C. for 6 hours. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 95/5) to obtain 1.57 g (64%, colorless liquid) of Compound 21.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.34-7.22 (m, 2H, Ar—H), 7.04-6.95 (m, 2H, Ar—H), 6.84-6. 73 (m, 2H, Ar- H), 4.04 (q, 2H, J = 7.0Hz, OCH 2), 3.70 (br, 2H, NH 2), 1.30 (t, 3H, J = 7.0 Hz, CH ₃ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物２１を０．８０１ｇ（３．１５ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５‐ｔｅｒｔ−ｂｕｔｙｌ‐２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを０．９３７ｇ（３．０ｍｍｏｌ）、アンバーリスト１５を９４ｍｇ加えトルエン２０ｍＬ加えた後、還流下で６時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物２２を０．９５０ｇ（収率 ５９％、黄色固体）得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.801 g (3.15 mmol) of compound 21 and 3-adamantyl-5-tert-2-butyl-2-hydroxydehydride 0.937 g (3.0 mmol), 94 mg of Amberlyst 15 and 20 mL of toluene were added, and the mixture was reacted for 6 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.950 g (yield 59%, yellow solid) of Compound 22.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.4 (s, 1H, OH), 8.54 (d, J = 2.4 Hz, 1H, N = CH), 7.28-7.16 (m, 4H, Ar-H), 7.00-6.84 (m, 4H, Ar-H), 3.97 (q, 2H, J = 6.9Hz, OCH 2), 2.38 (s, 3H, _{CH 3), 2.14-2.07 (s,} 9H, adamantyl), 1.77 (s, 6H, adamantyl), 1.27 (s, 9H, C (CH 3) 3), 1.26 ( t, 3H, J = 6.9 Hz, CH ₃ )

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を１．１ｍＬ（１．１ｍｍｏｌ）、トルエン２０ｍＬを加え−７８℃にドライアイス−メタノールバスにて冷却した。この混合液に化合物２２を０．５４０ｇ（１．０ｍｍｏｌ）をトルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１４時間反応させた。この反応液を減圧下で約３ｍＬまで濃縮した後に、ヘキサン１０ｍＬを加え析出させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物２３を０．６６０ｇ（収率 ９５％、オレンジ色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), add 1.1 mL (1.1 mmol) of a toluene solution of TiCl ₄ (1.0 mmol / mL) and 20 mL of toluene to a dry ice-methanol bath at −78 ° C. And cooled. In this mixed solution, 0.540 g (1.0 mmol) of Compound 22 was dissolved in 5 mL of toluene and dropped, and then reacted for 14 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 3 mL under reduced pressure, and 10 mL of hexane was added for precipitation. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.660 g of Compound 23 (yield 95%, orange solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.15 (d, 1H, J = 3.5 Hz, N = CH), 7.63 (d, 1H, J = 1.9 Hz, Ar—H), 7. 41-7.06 (m, 6H, Ar- H), 6.90 (s, 1H, Ar-H), 5.47-5.40 (m, 1H, OCH 2), 4.89-4. _{82 (m, 1H, OCH 2} ), 2.43 (s, 3H, CH 3), 2.27-2.16 (m, 9H, adamantyl), 1.93 (d, 3H, J = 12Hz, adamantyl ), 1.79 (d, 3H, J = 12 Hz, adamantyl), 1.28 (s, 9H, C (CH ₃ ) ₃ ), 1.02 (t, 3H, J = 7.0 Hz, CH ₃ )

[Synthesis Example 8]
(Synthesis of Compound 26)

充分に乾燥した２００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２‐ｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄを１．８３ｇ（１１．０ｍｍｏｌ）、２−ｂｒｏｍｏ−４，６−ｄｉｆｌｕｏｒｏａｎｉｌｉｎｅを２．０８ｇ（１０ｍｍｏｌ）、酢酸パラジウムを０．０１１ｇ（０．０５ｍｍｏｌ）、２‐Ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌを０．０４１ｇ（０．１ｍｍｏｌ）、リン酸カリウム一水和物６．９ｇ（３０ｍｍｏｌ）加え、トルエン２０ｍLに縣濁させ、１００℃で３時間反応させた。この反応液に水５０ｍLを加え、トルエンで抽出後、有機層をＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９２／８)を用いて精製することにより化合物２４を１．５４ｇ（６２％、白色固体）を得た。

In a well-dried 200 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer), 1.83 g (11.0 mmol) of 2-ethoxyphenylboronic acid and 2.08 g (10 mmol) of 2-bromo-4,6-difluoroaniline ), 0.011 g (0.05 mmol) of palladium acetate, 0.041 g (0.1 mmol) of 2-Dicyclohexylphosphino-2 ′, 6′-dimethylbiphenyl, 6.9 g (30 mmol) of potassium phosphate monohydrate, Suspended in 20 mL of toluene and reacted at 100 ° C. for 3 hours. 50 mL of water was added to the reaction solution, extracted with toluene, the organic layer was dried over MgSO ₄ , and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 92/8) to obtain 1.54 g (62%, white solid) of Compound 24.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.38-7.33 (m, 1H, Ar—H), 7.25-7.22 (m, 1H, Ar—H), 7.06-6. 98 (m, 2H, Ar- H), 6.83-6.67 (m, 2H, Ar-H), 4.06, (q, 2H, J = 6.9Hz, OCH 2), 3.67 (Br, 2H, NH ₂ ), 1.31 (t, 3H, J = 6.9 Hz, CH ₃ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物２４を０．６５４ｇ（２．６３ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５‐ｔｅｒｔ−ｂｕｔｙｌ‐２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを０．７８１ｇ（２．５ｍｍｏｌ）、アンバーリスト１５を７８ｍｇ加えトルエン４０ｍＬ加えた後、還流下で６時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物２５を０．９９１ｇ（収率 ７３％、黄色固体）得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean Stark tube, with Dimroth, with magnetic stirrer), compound 54 (0.654 g, 2.63 mmol), 3-adamantyl-5-tert-but-2-hydroxy-2-aldehyde 0.781 g (2.5 mmol), Amberlyst 15 78 mg and toluene 40 mL were added, followed by reaction under reflux for 6 hours. After removing insoluble matter from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.991 g of Compound 25 (yield 73%, yellow solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.2 (s, 1H, OH), 8.52 (d, J = 2.7 Hz, 1H, N = CH), 7.33-7.26 (m, 2H, Ar-H), 7.18-7.14 (m, 1H, Ar-H), 7.00-6.85 (m, 5H, Ar-H), 3.96 (q, 2H, J = 6.9 Hz, OCH ₂ ), 2.10 (s, 9 H, adamantyl), 1.78 (s, 6 H, adamantyl), 1.27 (s, 9 H, C (CH ₃ ) ₃ ), 1.26 (T, 3H, J = 6.9 Hz, CH ₃ )

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を１．１ｍＬ（１．１ｍｍｏｌ）、トルエン２０ｍＬを加え−７８℃にドライアイス−メタノールバスにて冷却した。この混合液に化合物２５を０．５４４ｇ（１．０ｍｍｏｌ）トルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１７時間反応させた。この反応液を減圧下で約３ｍＬまで濃縮した後に、ヘキサン１０ｍＬを加え析出させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物２６を０．５４０ｇ（収率 ７７％、赤紫色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), add 1.1 mL (1.1 mmol) of a toluene solution of TiCl ₄ (1.0 mmol / mL) and 20 mL of toluene to a dry ice-methanol bath at −78 ° C. And cooled. Compound 25 was dissolved in 0.544 g (1.0 mmol) of toluene in this mixed solution and dropped, and then reacted for 17 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 3 mL under reduced pressure, and 10 mL of hexane was added for precipitation. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.540 g (yield 77%, reddish purple solid) of Compound 26.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.15 (d, 1H, J = 3.0 Hz, N = CH), 7.65 (d, 1H, J = 2.2 Hz, Ar—H), 7. 43-7.26 (m, 5H, Ar-H), 7.06-6.99 (m, 1H, Ar-H), 6.87 (d, 1H, J = 8.4 Hz, Ar-H) , 5.49-5.42 (m, 1H, OCH 2), 4.88-4.81 (m, 1H, OCH 2), 2.27 (bs, 6H, adamantyl), 2.21 (bs, 3H, adamantyl), 1.93 (d, 3H, J = 12 Hz, adamantyl), 1.79 (d, 3H, J = 12 Hz, adamantyl), 1.28 (s, 9H, C (CH ₃ ) ₃ ) , 1.04 (t, 3H, J = 7.0 Hz, CH ₃ )

[Synthesis Example 9]
(Synthesis of Compound 29)

充分に乾燥した５０ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２−Ｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄ（東京化成工業株式会社製）を０．５０ｇ（３．０ｍｍｏｌ）、２−Ｃｈｌｏｒｏ−４−ｆｌｕｏｒｏａｎｉｌｉｎｅ（和光純薬工業株式会社製）を０．３４ｍＬ（２．９ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．００８ｇ（０．０２８ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）０．９９ｇ（３．１ｍｍｏｌ）加え、イソプロピルアルコール（関東化学株式会社製）２０ｍＬに溶解させ、８０℃で６時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９／１）を用いて精製することにより化合物２７を０．６６ｇ（１００％、淡褐色液体）得た。

To a well-dried 50 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer), 0.50 g (3.0 mmol) of 2-Ethoxyphenylboronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.), 2-Chloro-4-fluorineline 0.34 mL (2.9 mmol) (manufactured by Wako Pure Chemical Industries, Ltd.), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) -chloride (Sigma Aldrich Japan Co., Ltd.) 0.008 g (0.028 mmol), barium hydroxide octahydrate (manufactured by Wako Pure Chemical Industries, Ltd.) 0.99 g (3.1 mmol), and dissolved in 20 mL of isopropyl alcohol (manufactured by Kanto Chemical Co., Inc.) And allowed to react at 80 ° C. for 6 hours. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 9/1) to obtain 0.66 g (100%, light brown liquid) of Compound 27.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.37-7.30 (m, 1H, Ar—H), 7.26-7.23 (m, 1H, Ar—H), 7.06-6. 98 (m, 2H, Ar-H), 6.91-6.83 (m, 2H, Ar-H), 6.72-6.66 (m, 1H, Ar-H), 4.06 (q , 2H, J = 6.9 Hz, OCH ₂ ), 3.62 (bs, 2H, NH ₂ ), 1.31 (t, 3H, J = 6.9 Hz, OCH ₂ CH ₃ )

充分に乾燥した５０ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物２７を０．６３ｇ（２．９ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５−ｔｅｒｔ−ｂｕｔｙｌ−２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを０．８２ｇ（２．６ｍｍｏｌ）、アンバーリスト１５（Ｈ）を２００ｍｇ、トルエン２０ｍＬを加えた後、還流下で２０時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、メタノールから再結晶することにより化合物２８を０．９４ｇ（収率 ６８％、黄色固体）得た。

In a well-dried 50 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.63 g (2.9 mmol) of compound 27, 3-adamantyl-5-tert-butyl-2-hydroxybenzaldehyde 0.82 g (2.6 mmol), 200 mg of Amberlyst 15 (H) and 20 mL of toluene were added, followed by reaction for 20 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from methanol gave 0.94 g of Compound 28 (yield 68%, yellow solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.4 (s, 1H, OH), 8.47 (s, 1H, N═CH), 7.34-7.27 (m, 2H, Ar—H) 7.19-7.05 (m, 5H, Ar-H), 699-6.90 (m, 2H, Ar-H), 4.01 (q, 2H, J = 6.9 Hz, OCH) ₂ ), 2.10 (s, 6H, adamantyl), 2.06 (s, 3H, adamantyl), 1.77 (s, 6H, adamantyl), 1.29 (s, 9H, tert-Butyl), 1 .24 (t, 3H, J = 6.9 Hz, OCH ₂ CH ₃ )

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を１．０ｍＬ（１．０ｍｍｏｌ）、トルエン５ｍＬを加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物２８を０．４３９ｇ（０．８４ｍｍｏｌ）をトルエン１０ｍＬに溶かして滴下した後、室温まで昇温させつつ１６時間反応させた。この反応液を減圧下で約０．８ｍＬまで濃縮した後、ヘキサン１０ｍＬを加え析出させ、析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物２９を０．３９３ｇ（収率 ６８％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 1.0 mL (1.0 mmol) of 1.0 M toluene solution of titanium tetrachloride and 5 mL of toluene were added, and cooled to -78 ° C with a dry ice-acetone bath. . To this, 0.439 g (0.84 mmol) of Compound 28 was dissolved in 10 mL of toluene and dropped, and then reacted for 16 hours while raising the temperature to room temperature. After concentrating the reaction solution to about 0.8 mL under reduced pressure, 10 mL of hexane was added for precipitation, and the precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.393 g (yield). 68%, reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.15 (s, 1H, HC = N), 7.63 (d, 1H, J = 2.7 Hz, Ar—H), 7.45-7.43 ( m, 2H, Ar-H), 7.33-7.28 (m, 3H, Ar-H), 7.19-6.98 (m, 3H, Ar-H), 5.54-5.41. _{(m, 1H, OCH 2)} , 4.89-4.77 (m, 1H, OCH 2), 2.27-2.16 (m, 9H, adamantyl), 1.95-1.77 (m, 6H, Adamantyl), 1.28 (s, 9H, tert-Butyl), 1.00 (t, 3H, J = 6.9 Hz, OCH ₂ CH ₃ )

[Synthesis Example 10]
(Synthesis of Compound 32)

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２−（４,４,５,５−ｔｅｔｒａｍｅｔｈｙｌ−１,３,２−ｄｉｏｘａｂｏｒｏｌａｎ−２−ｙｌ）ａｎｉｌｉｎｅ（東京化成工業株式会社製）を２．４１ｇ（１１ｍｍｏｌ）、２−ｃｈｌｏｒｏ−６−ｆｌｕｏｒｏａｎｉｓｏｌｅを１．６１ｇ（１０ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．０２９ｇ（０．０５ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）４．７３ｇ（１５ｍｍｏｌ）加え、イソプロピルアルコール５０ｍＬに溶解させ、８０℃で６時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９／１）を用いて精製することにより化合物３０を１．３７ｇ（６３％、白色固体）得た。

2- (4,4,5,5-tetramethyl-1,3,2-dioxabolan-2-yl) aniline (Tokyo Kasei) in a well-dried 100 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer) Kogyo Co., Ltd.) 2.41 g (11 mmol), 2-chloro-6-fluoroanisole 1.61 g (10 mmol), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) ) -Chloride (Sigma Aldrich Japan Co., Ltd.) 0.029 g (0.05 mmol), Barium hydroxide octahydrate (Wako Pure Chemical Industries, Ltd.) 4.73 g (15 mmol) was added and dissolved in 50 mL of isopropyl alcohol. The And reacted for 6 hours at 80 ° C.. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 9/1) to obtain 1.37 g (63%, white solid) of Compound 30.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.25-7.02 (m, 5H, Ar—H), 6.85-6.76 (m, 2H, Ar—H), 3.74 (br, 2H, NH ₂ ), 3.71 (d, 3H, J = 1.4 Hz, OCH ₃ )

充分に乾燥した１００ｍLナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物３０を０．９１２ｇ（４．２ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５‐ｍｅｔｈｙｌ‐２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを１．０８ｇ（４．０ｍｍｏｌ）、アンバーリスト１５を１０８ｍｇ加えトルエン４０ｍＬ加えた後、還流下で６時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物３１を１．５２ｇ（８１％、黄色固体）を得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.912 g (4.2 mmol) of compound 30 and 3-adamantyl-5-methyl-2-hydroxybenzaldehyde 1 0.08 g (4.0 mmol) and 108 mg of Amberlyst 15 were added, and 40 mL of toluene was added, followed by 6 hours of reaction under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 1.52 g (81%, yellow solid) of Compound 31.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.2 (s, 1H, OH), 8.53 (s, 1H, N═CH), 7.48-7.26 (m, 4H, Ar—H) , 7.13-6.95 (m, 5H, Ar -H), 3.69 (d, 3H, J = 2.2Hz, OCH 3), 2.27 (s, 3H, CH 3), 2. 07 (s, 9H, adamantyl), 1.76 (s, 6H, adamantyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を１．６５ｍＬ（１．６５ｍｍｏｌ）、トルエン２０ｍＬを加え−７８℃にドライアイス−メタノールバスにて冷却した。この混合液に化合物３１を０．６９０ｇ（１．５ｍｍｏｌ）をトルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１９時間反応させた。この反応液を減圧下で約３ｍＬまで濃縮した後に、ヘキサン１０ｍＬを加え析出させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物３２を０．７６６ｇ（収率 ８２％、赤紫色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), add 1.65 mL (1.65 mmol) of a TiCl ₄ toluene solution (1.0 mmol / mL) and 20 mL of toluene to a dry ice-methanol bath at −78 ° C. And cooled. In this mixed solution, 0.690 g (1.5 mmol) of Compound 31 was dissolved in 5 mL of toluene and dropped, and then reacted for 19 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 3 mL under reduced pressure, and 10 mL of hexane was added for precipitation. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.766 g of Compound 32 (yield 82%, red purple solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.13 (s, 1H, N═CH), 7.54-7.44 (m, 2H, Ar—H), 7.39 (d, 1H, J = 1.9 Hz, Ar-H), 7.34-7.28 (m, 2H, Ar-H), 7.20-7.04 (m, 4H, Ar-H), 4.45 (s, 3H) , OCH ₃ ), 2.33 (s, 3H, CH ₃ ), 2.6-2.19 (m, 9H, adamantyl), 2.14 (s, 6H, adamantyl), 1.92 (d, 3H , J = 12 Hz, adamantyl), 1.78 (d, 3H, J = 12 Hz, adamantyl)

[Synthesis Example 11]
(Synthesis of Compound 36)

充分に乾燥した３００ｍＬ三口ナスフラスコ（滴下ロート、三方コック付、磁気攪拌子入り）に４−ｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌ（東京化成工業株式会社製）を９．２１ｇ（５０．０ｍｍｏｌ）、ヘキサン６０ｍＬを加え、氷浴にて０℃まで冷却した後、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（東京化成工業株式会社製）７．９ｍＬ（５２．５ｍｍｏｌ）を加え、ノルマルブチルリチウムのヘキサン溶液（１．６ｍｏｌ／Ｌ）３２．８ｍＬ（５２．５ｍｍｏｌ）を滴下した後、１６時間反応させた。５００ｍＬ三口ナスフラスコ（三方コック付、磁気攪拌子入り）にヘキサン６０ｍＬ、ホウ酸トリメチル（シグマ アルドリッチ ジャパン 株式会社製）１６．８ｍＬ（１５０ｍｍｏｌ）を加えた後、−７８℃に冷却した後に、先ほど調製した反応液を滴下し、そのまま室温まで昇温させつつ３時間反応させた。この反応液に飽和塩化アンモニウム水溶液５０ｍＬを加えた後、酢酸エチル５０ｍＬ×３で抽出後、有機層を純水５０ｍＬ×２で洗浄し、ＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより、粗生成物を得た。得られた粗生成物をヘキサンから再沈殿することにより、化合物３３を６．６７ｇ（６０％、白色固体）得た。

9.21 g (50.0 mmol) of 4-methoxybiphenyl (manufactured by Tokyo Chemical Industry Co., Ltd.) and 60 mL of hexane are added to a well-dried 300 mL three-necked eggplant flask (with a dropping funnel, with a three-way cock, and a magnetic stirrer), and an ice bath is added. After cooling to 0 ° C., 7.9 mL (52.5 mmol) of N, N, N ′, N′-tetramethylethylenediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) was added, and a hexane solution of normal butyl lithium (1. (6 mol / L) 32.8 mL (52.5 mmol) was added dropwise, followed by reaction for 16 hours. After adding 60 mL of hexane and 16.8 mL (150 mmol) of trimethyl borate (manufactured by Sigma Aldrich Japan Co., Ltd.) to a 500 mL three-necked eggplant flask (with a three-way cock, with a magnetic stirrer), the mixture was cooled to -78 ° C. and then prepared earlier. The reaction solution was added dropwise and allowed to react for 3 hours while raising the temperature to room temperature. After adding 50 mL of saturated aqueous ammonium chloride solution to this reaction solution, and extracting with 50 mL × 3 ethyl acetate, the organic layer is washed with 50 mL × 2 pure water, dried over MgSO ₄ , and the solvent is distilled off under reduced pressure. Gave a crude product. The obtained crude product was reprecipitated from hexane to obtain 6.67 g (60%, white solid) of Compound 33.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.10 (d, J = 2.6 Hz, 1H, Ar—H), 7.68 (dd, J = 8.6 Hz, 2.6 Hz, 1H, Ar—H) ), 7.59 (m, 2H, Ar-H), 7.42 (m, 2H, Ar-H), 7.31 (m, 1H, Ar-H), 7.00 (d, J = 8) .6 Hz, 1 H, Ar—H), 6.05 (s, 2 H, B (OH) ₂ ), 3.96 (s, 3 H, OCH ₃ )

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に化合物３３を１．０ｇ（４．４ｍｍｏｌ）、２−ｂｒｏｍｏ−４，６−ｄｉｆｌｕｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を０．９１ｇ（４．４ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．０１３ｇ（０．０２２ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）１．５ｇ（４．６ｍｍｏｌ）加え、イソプロピルアルコール（関東化学株式会社製）３０ｍＬに溶解させ、８０℃で３時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝１０／１）を用いて精製することにより化合物３４を１．１６ｇ（８９％、淡褐色液体）得た。

In a well-dried 100 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer), 1.0 g (4.4 mmol) of compound 33, 2-bromo-4,6-difluoroaniline (manufactured by Tokyo Chemical Industry Co., Ltd.) 0.91 g (4.4 mmol), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -paladium (II) -chloride (manufactured by Sigma Aldrich Japan Co., Ltd.) 0.013 g (0. 022 mmol), 1.5 g (4.6 mmol) of barium hydroxide octahydrate (manufactured by Wako Pure Chemical Industries, Ltd.), dissolved in 30 mL of isopropyl alcohol (manufactured by Kanto Chemical Co., Ltd.), and reacted at 80 ° C. for 3 hours. It was. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 10/1) to obtain 1.16 g (89%, light brown liquid) of Compound 34.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.64-7.28 (m, 7H, Ar—H), 7.08 (d, J = 8.6 Hz, 1H, Ar—H), 6.86— 6.72 (m, 2H, Ar- H), 3.87 (s, 3H, OCH 3), 3.66 (bs, 2H, NH 2)

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物３４を０．７０ｇ（２．２ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｐｈｅｎｙｌｂｅｎｚａｌｄｅｈｙｄｅ０．７４６ｇ（２．２ｍｍｏｌ）、アンバーリスト１５（Ｈ）を３２１ｍｇ、トルエン３０ｍＬを加えた後、還流下で３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物３５を１．３４ｇ（収率 ５５％、黄色固体）得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.70 g (2.2 mmol) of compound 34, 3-adamantyl-2-hydroxy-5-phenylbenzaldehyde 0.746 g (2.2 mmol) and 321 mg of Amberlyst 15 (H) and 30 mL of toluene were added, and the mixture was reacted for 3 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 1.34 g (yield 55%, yellow solid) of Compound 35.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.8 (s, 1H, OH), 8.62 (s, 1H, N═CH), 7.61-7.27 (m, 16H, Ar—H) 7.03 (d, J = 8.2 Hz, 1H, Ar—H), 3.81 (s, 3H, OCH ₃ ), 2.15 to 2.05 (m, 9H, adamantyl), 1.76. (S, 6H, adamantyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を０．４ｍＬ（０．４ｍｍｏｌ）、ヘキサンを２０ｍＬ加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物３５を０．２７５ｇ（０．４４ｍｍｏｌ）をトルエン１ｍＬ／ヘキサン１５ｍＬに溶かしたものを滴下した後、室温まで昇温させつつ２時間反応させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物３６を０．２６０ｇ（収率 ８２％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 0.4 mL (0.4 mmol) of a 1.0 M toluene solution of titanium tetrachloride and 20 mL of hexane were added, and cooled to −78 ° C. with a dry ice-acetone bath. . A solution prepared by dissolving 0.275 g (0.44 mmol) of Compound 35 in 1 mL of toluene / 15 mL of hexane was added dropwise thereto, and then reacted for 2 hours while raising the temperature to room temperature. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.260 g (yield 82%, reddish brown solid) of Compound 36.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.25 (d, J = 2.6 Hz, 1H, HC = N), 7.83 (d, J = 2.3 Hz, 1H, Ar—H), 7. 65-6.99 (m, 16H, Ar-H), 4.48 (s, 3H, OCH ₃ ), 2.28 (m, 6H, adamantyl), 2.91 (m, 3H, adamantyl), 1 .96 (d, J = 12.5 Hz, 3H, adamantyl), 1.82 (d, J = 12.5 Hz, 3H, adamantyl)

[Synthesis Example 12]
(Synthesis of Compound 41)

充分に乾燥した２００ｍＬ二口ナスフラスコ（三方コック付、磁気攪拌子入り）に４−ｃｕｍｙｌｐｈｅｎｏｌ（和光純薬工業株式会社製）を５．０ｇ（２３．５ｍｍｏｌ）、炭酸カリウムを４．９ｇ（３５．３ｍｍｏｌ）加え、アセトン８０ｍＬに溶解させた。溶液を４５℃に昇温した後、ヨウ化メチル（和光純薬工業株式会社製）２．１９ｍＬ（３５．３ｍｍｏｌ）をゆっくり滴下したのち、４５℃に保って３時間反応させた。反応終了後、反応液から不溶分をろ別し、飽和塩化アンモニウム水溶液を加えて酢酸エチルで抽出し、有機層を水で洗浄、無水硫酸ナトリウムで乾燥した。溶媒を減圧下で留去、得られた粗生成物をシリカゲルカラムクロマトグラフィー（展開溶媒：ヘキサン）で精製することにより、化合物３７を３．８８ｇ（７３％、無色液体）得た。

In a well-dried 200 mL two-necked eggplant flask (with a three-way cock, with a magnetic stirrer), 5.0 g (23.5 mmol) of 4-cumylphenol (manufactured by Wako Pure Chemical Industries, Ltd.) and 4.9 g of potassium carbonate (35 .3 mmol) and dissolved in 80 mL of acetone. After the temperature of the solution was raised to 45 ° C., 2.19 mL (35.3 mmol) of methyl iodide (manufactured by Wako Pure Chemical Industries, Ltd.) was slowly added dropwise, and the reaction was carried out for 3 hours while maintaining the temperature at 45 ° C. After completion of the reaction, insoluble matter was filtered off from the reaction solution, a saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The solvent was distilled off under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (developing solvent: hexane) to obtain 3.88 g (73%, colorless liquid) of Compound 37.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.29-7.12 (m, 7H, Ar—H), 6.80 (d, J = 8.9 Hz, 2H, Ar—H), 3.78 ( s, 3H, OCH ₃ ), 1.66 (s, 6H, cumyl)

充分に乾燥した３００ｍＬ三口ナスフラスコ（滴下ロート、三方コック付、磁気攪拌子入り）に化合物３７を２．６ｇ（１１．５ｍｍｏｌ）、ヘキサン３０ｍＬを加え、氷浴にて０℃まで冷却した後、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン（東京化成工業株式会社製）１．８２ｍＬ（１２．１ｍｍｏｌ）を加え、ノルマルブチルリチウムのヘキサン溶液（１．６ｍｏｌ／Ｌ）７．５５ｍＬ（１２．１ｍｍｏｌ）を滴下した後、１６時間反応させた。５００ｍＬ三口ナスフラスコ（三方コック付、磁気攪拌子入り）にヘキサン４０ｍＬ、ホウ酸トリメチル（シグマ アルドリッチ ジャパン 株式会社製）３．８５ｍＬ（３４．５ｍｍｏｌ）を加えた後、−７８℃に冷却した後に、先ほど調製した反応液を滴下し、そのまま室温まで昇温させつつ３時間反応させた。この反応液に飽和塩化アンモニウム水溶液５０ｍＬを加えた後、酢酸エチル５０ｍＬ×３で抽出後、有機層を純水５０ｍＬ×２で洗浄し、ＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより、粗生成物を得た。得られた粗生成物をヘキサンから再沈殿することにより、化合物３８を２．２ｇ（７１％、白色固体）得た。

2.6 g (11.5 mmol) of Compound 37 and 30 mL of hexane were added to a well-dried 300 mL three-necked eggplant flask (with a dropping funnel, with a three-way cock, and a magnetic stirrer), and cooled to 0 ° C. in an ice bath. N, N, N ′, N′-tetramethylethylenediamine (manufactured by Tokyo Chemical Industry Co., Ltd.) 1.82 mL (12.1 mmol) was added, and hexane solution of normal butyl lithium (1.6 mol / L) 7.55 mL (12 0.1 mmol) was added dropwise, followed by reaction for 16 hours. After adding 40 mL of hexane and 3.85 mL (34.5 mmol) of trimethyl borate (manufactured by Sigma Aldrich Japan Co., Ltd.) to a 500 mL three-necked eggplant flask (with a three-way cock, containing a magnetic stirrer), the mixture was cooled to −78 ° C. The reaction solution prepared earlier was added dropwise and reacted for 3 hours while raising the temperature to room temperature. After adding 50 mL of saturated aqueous ammonium chloride solution to this reaction solution, and extracting with 50 mL × 3 ethyl acetate, the organic layer is washed with 50 mL × 2 pure water, dried over MgSO ₄ , and the solvent is distilled off under reduced pressure. Gave a crude product. The obtained crude product was reprecipitated from hexane to obtain 2.2 g (71%, white solid) of Compound 38.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.80 (d, 2.6 Hz, 1H, Ar—H), 7.29-7.13 (m, 6H, Ar—H), 6.81 (d, J = 8.6 Hz, 1H, Ar—H), 5.95 (s, 2H, B (OH) ₂ ), 3.88 (s, 3H, OCH ₃ ), 1.69 (s, 6H, cumyl)

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に化合物３８を１．０ｇ（３．７ｍｍｏｌ）、２−ｂｒｏｍｏ−４，６−ｄｉｆｌｕｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を０．７７ｇ（３．９ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．０１１ｇ（０．０１９ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）１．２ｇ（３．９ｍｍｏｌ）加え、イソプロピルアルコール（関東化学株式会社製）３０ｍＬに溶解させ、８０℃で３時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝１０／１）を用いて精製することにより化合物３９を０．６８ｇ（５４％、淡褐色液体）得た。

1.0 g (3.7 mmol) of compound 38, 2-bromo-4,6-difluoroaniline (manufactured by Tokyo Chemical Industry Co., Ltd.) in a well-dried 100 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer) 0.77 g (3.9 mmol), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) -chloride (manufactured by Sigma Aldrich Japan Co., Ltd.) 019 mmol), 1.2 g (3.9 mmol) of barium hydroxide octahydrate (manufactured by Wako Pure Chemical Industries, Ltd.), dissolved in 30 mL of isopropyl alcohol (manufactured by Kanto Chemical Co., Ltd.), and reacted at 80 ° C. for 3 hours. It was. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 10/1) to obtain 0.68 g (54%, light brown liquid) of Compound 39.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.31-7.11 (m, 7H, Ar—H), 6.90 (d, J = 8.9 Hz, 1H, Ar—H), 6.77 ( m, 1H, Ar-H) , 6.66 (m, 1H, Ar-H), 3.80 (s, 3H, OCH 3), 3.60 (bs, 2H, NH 2), 1.68 ( s, 6H, cumyl)

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物３９を０．６８ｇ（１．９ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｐｈｅｎｙｌｂｅｎｚａｌｄｅｈｙｄｅ０．６３ｇ（１．９ｍｍｏｌ）、アンバーリスト１５（Ｈ）を１９０ｍｇ、トルエン３０ｍＬを加えた後、還流下で３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物４０を０．５３３ｇ（収率 ４４％、黄色固体）得た。

0.68 g (1.9 mmol) of Compound 39 in a well-dried 100 mL eggplant flask (three-way cock, Dean Stark tube, with Dimroth, with magnetic stirrer), 0.63 g of 3-adamantyl-2-hydroxy-5-phenylbenzaldehyde (1.9 mmol), 190 mg of Amberlyst 15 (H) and 30 mL of toluene were added, and the mixture was reacted under reflux for 3 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.533 g (yield 44%, yellow solid) of Compound 40.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.3 (s, 1H, OH), 8.54 (d, J = 2.0 Hz, 1H, N = CH), 7.55-7.30 (m, 6H), 7.20-7.04 (m, 8H, Ar-H), 6.90 (d, J = 8.6 Hz, 2H, Ar-H), 6.81 (d, J = 8.6 Hz). , 1H, Ar-H), 3.69 (s, 3H, OCH 3), 2.17 (s, 6H, adamantyl), 2.08 (s, 3H, adamantyl), 1.78 (s, 6H, adamantyl), 1.64 (s, 6H, cumyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁ｎ気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を０．３５ｍＬ（０．３５ｍｍｏｌ）、ヘキサンを１５ｍＬ加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物４０を０．２５７ｇ（０．３９ｍｍｏｌ）をトルエン１ｍＬ／ヘキサン１５ｍＬに溶かしたものを滴下した後、室温まで昇温させつつ２時間反応させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物４１を０．２１５ｇ（収率 ７４％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), add 0.35 mL (0.35 mmol) of 1.0 M toluene solution of titanium tetrachloride and 15 mL of hexane, and bring it to -78 ° C with a dry ice-acetone bath. Cooled down. A solution prepared by dissolving 0.257 g (0.39 mmol) of Compound 40 in 1 mL of toluene / 15 mL of hexane was added dropwise thereto, and then reacted for 2 hours while raising the temperature to room temperature. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.215 g of Compound 41 (yield 74%, reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.16 (d, J = 2.3 Hz, 1H, HC = N), 7.84 (d, J = 2.3 Hz, 1H, Ar—H), 7. 54-6.99 (m, 15H, Ar- H), 6.86 (d, J = 8.6Hz, 1H, Ar-H), 4.39 (s, 3H, OCH 3), 2.27- 2.12 (m, 9H, adamantyl), 1.94 (d, J = 10.9 Hz, 3H, adamantyl), 1.81 (d, J = 10.9 Hz, 3H, adamantyl), 1.63 (s , 6H, cumyl)

[Synthesis Example 13]
(Synthesis of Compound 47)

充分に乾燥した２００ｍＬ四口ナスフラスコ（三方コック付、磁気攪拌子入り）に３，４−Ｄｉｈｙｒｏ−２Ｈ−ｐｙｒａｎ（和光純薬工業株式会社製）を５．１９ｇ（６１．７ｍｍｏｌ）加え、ジクロロメタン（関東化学株式会社製）４８ｍＬに溶解させた。０℃に冷却した後、塩化水素の２．０Ｍジエチルエーテル溶液（シグマ アルドリッチ ジャパン 株式会社製）０．１６ｍＬ（０．３２ｍｍｏｌ）を加え、その後、４−Ｔｒｉｆｌｕｏｒｏｍｅｔｈｙｌｐｈｅｎｏｌ（シグマ アルドリッチ ジャパン 株式会社製）の４．００ｇ（２４．７ｍｍｏｌ）をジクロロメタン２４ｍＬに溶解させ、滴下ロート経由で１３分かけて加えた。室温で終夜攪拌した後、飽和重曹水を加えてジクロロメタンで抽出し、水、ついで飽和食塩水で洗浄した。無水硫酸ナトリウムで乾燥し、固体を濾過で取り除いて、溶媒を減圧下で留去することにより、化合物４２を８．１４ｇ（１００％、淡黄色液体）得た。

5.19 g (61.7 mmol) of 3,4-Dihyro-2H-pyran (manufactured by Wako Pure Chemical Industries, Ltd.) was added to a well-dried 200 mL four-necked eggplant flask (with a three-way cock, with a magnetic stirrer), and dichloromethane. It was dissolved in 48 mL (manufactured by Kanto Chemical Co., Inc.). After cooling to 0 ° C., 0.16 mL (0.32 mmol) of 2.0 M diethyl ether solution of hydrogen chloride (Sigma Aldrich Japan Co., Ltd.) was added, and then 4 of 4-Trifluoromethylphenol (manufactured by Sigma Aldrich Japan Co., Ltd.) was added. 0.000 g (24.7 mmol) was dissolved in 24 mL of dichloromethane and added via a dropping funnel over 13 minutes. After stirring overnight at room temperature, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with dichloromethane, washed with water and then with saturated brine. After drying over anhydrous sodium sulfate, the solid was removed by filtration, and the solvent was distilled off under reduced pressure to obtain 8.14 g (100%, pale yellow liquid) of Compound 42.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.53 (d, 2H, J = 9.2 Hz, Ar—H), 7.11 (d, 2H, J = 9.2 Hz, Ar—H), 5. 48 (t, 1H, J = 3.0 Hz, OCHO), 3.86 (ddd, 1H, J = 11.2, 9.7, 3.0 Hz, OCH ₂ ), 3.62 (dtd, 1H, J = 11.2, 4.0, 1.5 Hz, OCH ₂ ), 2.08-1.57 (m, 6H, CH ₂ CH ₂ CH ₂ )

充分に乾燥した２００ｍＬ四口ナスフラスコ（三方コック付、磁気攪拌子入り）にｎ−ブチルリチウムの１．５９Ｍヘキサン溶液（関東化学株式会社製）２０ｍＬを加え、−７８℃に冷却した。化合物４２の７．０８ｇ（２１．６ｍｍｏｌ）をテトラヒドロフラン５０ｍＬに溶解させて２２分かけて滴下ロートから加えた。１時間同温度で攪拌した後、１，２−Ｄｉｂｒｏｍｏ−１，１，２，２−ｔｅｔｒａｆｌｕｏｒｏｅｔｈａｎｅ（東京化成工業株式会社製）をテトラヒドロフラン２５ｍＬに溶解させて１３分かけて滴下ロートから加えた。室温まで昇温して終夜攪拌した後、水を加えて酢酸エチルで抽出し、水、ついで飽和食塩水で洗浄した。無水硫酸ナトリウムで乾燥し、固体を濾過で取り除いて、溶媒を減圧下で留去することにより、化合物４３を９．３２ｇ（９６％、淡黄色液体）得た。

20 mL of a 1.59M hexane solution (manufactured by Kanto Chemical Co., Inc.) of n-butyllithium was added to a well-dried 200 mL four-necked eggplant flask (with a three-way cock, with a magnetic stirrer), and cooled to -78 ° C. 7.08 g (21.6 mmol) of Compound 42 was dissolved in 50 mL of tetrahydrofuran and added through a dropping funnel over 22 minutes. After stirring at the same temperature for 1 hour, 1,2-Dibromo-1,1,2,2-tetrafluoroethane (manufactured by Tokyo Chemical Industry Co., Ltd.) was dissolved in 25 mL of tetrahydrofuran and added from a dropping funnel over 13 minutes. After warming to room temperature and stirring overnight, water was added and the mixture was extracted with ethyl acetate, washed with water and then with saturated brine. The extract was dried over anhydrous sodium sulfate, the solid was removed by filtration, and the solvent was distilled off under reduced pressure to obtain 9.32 g (96%, pale yellow liquid) of Compound 43.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.80 (d, 1H, J = 2.4 Hz, Ar—H), 7.50 (dd, 1H, J = 8.3, 2.4 Hz, Ar—H ), 7.22 (d, 1H, J = 8.3 Hz, Ar-H), 5.60 (t, 1H, J = 2.7 Hz, OCHO), 3.82 (td, 1H, J = 1.11. 0, 3.1 Hz, OCH ₂ ), 3.66-3.59 (m, 1H, OCH ₂ ), 2.18-1.59 (m, 6H, CH ₂ CH ₂ CH ₂ )

充分に乾燥した５００ｍＬ四口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）にＴｅｔｒａｋｉｓ（ｔｒｉｐｈｅｎｙｌｐｈｏｓｐｈｉｎｅ）ｐａｌｌａｄｉｕｍ（０）（東京化成工業株式会社製）を１．２１ｇ（１．０５ｍｍｏｌ）、化合物４３を８．８４ｇ（２０．９ｍｍｏｌ）加え、テトラヒドロフラン１３３ｍＬに溶解させた。次いで、１−Ａｄａｍａｎｔｙｌｚｉｎｃ ｂｒｏｍｉｄｅの０．５Ｍテトロヒドロフラン溶液（シグマ アルドリッチ ジャパン 株式会社製）を６７ｍＬ加え、７０℃で１１時間反応させた。反応溶液を室温まで冷却した後、Ｔｅｔｒａｋｉｓ（ｔｒｉｐｈｅｎｙｌｐｈｏｓｐｈｉｎｅ）ｐａｌｌａｄｉｕｍ（０）を１．２１ｇ（１．０５ｍｍｏｌ）追加し、７０℃で１４時間４０分反応させた。０℃に冷却してから濃塩酸（関東化学株式会社製）３３ｍＬと水２２ｍＬを加えて室温で終夜攪拌し、溶媒を減圧下で留去した。残渣をジクロロメタンに溶解させた後、水と食塩水で洗浄し、無水硫酸ナトリウム（東京化成工業株式会社製）を加えて乾燥させた。固体を濾過で取り除いて、溶媒を減圧下で留去することにより粗生成物を得、これをシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝２４／１）で精製することで、化合物４４を２．９５ｇ（４８％、淡黄色液体）得た。

1.21 g (1.05 mmol) of Tetrakis (triphenylphosphine) palladium (0) (manufactured by Tokyo Chemical Industry Co., Ltd.) in a well-dried 500 mL four-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer), Compound 43 8.84 g (20.9 mmol) was added and dissolved in 133 mL of tetrahydrofuran. Subsequently, 67 mL of 0.5M tetrohydrofuran solution (manufactured by Sigma Aldrich Japan Co., Ltd.) of 1-Adamantylzinc bromide was added and reacted at 70 ° C. for 11 hours. After cooling the reaction solution to room temperature, 1.21 g (1.05 mmol) of Tetrakis (triphenylphosphine) palladium (0) was added and reacted at 70 ° C. for 14 hours and 40 minutes. After cooling to 0 ° C., 33 mL of concentrated hydrochloric acid (manufactured by Kanto Chemical Co., Inc.) and 22 mL of water were added and stirred overnight at room temperature, and the solvent was distilled off under reduced pressure. The residue was dissolved in dichloromethane, washed with water and brine, and dried over anhydrous sodium sulfate (manufactured by Tokyo Chemical Industry Co., Ltd.). The solid was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 24/1) to give compound 44. 2.95 g (48%, pale yellow liquid) was obtained.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.46 (d, 1H, J = 2.1 Hz, Ar—H), 7.32 (dd, 1H, J = 8.1, 2.1 Hz, Ar—H) ), 6.70 (d, 1H, J = 8.1 Hz, Ar-H), 5.18 (s, 1H, OH), 2.12-2.09 (m, 9H, Adamantyl), 1.79. -1.78 (m, 6H, Adamantyl)

充分に乾燥した１００ｍＬ四口ナスフラスコ（三方コック付、磁気攪拌子入り）に３，４−Ｄｉｈｙｒｏ−２Ｈ−ｐｙｒａｎを２．０９ｇ（２４．８ｍｍｏｌ）加えてジクロロメタン２０ｍＬに溶解させた。０℃に冷却した後、塩化水素の２．０Ｍジエチルエーテル溶液０．０５ｍＬ（０．１ｍｍｏｌ）を加え、その後、化合物４４の２．９５ｇ（９．９６ｍｍｏｌ）をジクロロメタン２０ｍＬに溶解させ、滴下ロート経由で１３分かけて加えた。終夜攪拌の後、３，４−Ｄｉｈｙｒｏ−２Ｈ−ｐｙｒａｎの２．０９ｇ（２４．８ｍｍｏｌ）を２回に分けて追加して反応を継続した。１６時間後、重曹水を加えてジクロロメタンで抽出し、その後、水と食塩水で洗浄して無水硫酸ナトリウムで乾燥した。固体を濾過で取り除いて、溶媒を減圧下で留去することにより、３．５９ｇの淡黄色固体を得た。この固体を充分に乾燥した３００ｍＬ四口ナスフラスコ（三方コック付、磁気攪拌子入り）内でテトラヒドロフラン１００ｍＬに溶解させ、−７８℃に冷却した。ｎ−ブチルリチウムの１．５９Ｍヘキサン溶液を９．０ｍＬ（１４．３ｍｍｏｌ）加えて１時間反応させた後、Ｎ，Ｎ−ジメチルホルムアミド（関東化学株式会社製）を２ｍＬ（２５．８ｍｍｏｌ）加え、室温に昇温して６３時間攪拌した。０℃に冷却した後、濃塩酸１５ｍＬと水１０ｍＬを加えて終夜攪拌し、溶媒を減圧下で留去した。残渣をジクロロメタンで抽出し、水と食塩水で洗浄して無水硫酸ナトリウムで乾燥させた。固体を濾過によって取り除き、溶媒を減圧下で留去して粗生成物を得、これをシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝４９／１）を用いて精製することにより化合物４５を８０６ｍｇ（２９％、淡黄色固体）得た。

2.09 g (24.8 mmol) of 3,4-Dihyro-2H-pyran was added to a well-dried 100 mL four-necked eggplant flask (with a three-way cock, with a magnetic stirring bar), and dissolved in 20 mL of dichloromethane. After cooling to 0 ° C., 0.05 mL (0.1 mmol) of a 2.0 M solution of hydrogen chloride in diethyl ether was added, and then 2.95 g (9.96 mmol) of Compound 44 was dissolved in 20 mL of dichloromethane and passed through a dropping funnel. Over 13 minutes. After stirring overnight, 2.09 g (24.8 mmol) of 3,4-Dihyro-2H-pyran was added in two portions and the reaction was continued. After 16 hours, aqueous sodium bicarbonate was added and extracted with dichloromethane, then washed with water and brine and dried over anhydrous sodium sulfate. The solid was removed by filtration, and the solvent was distilled off under reduced pressure to obtain 3.59 g of a pale yellow solid. This solid was dissolved in 100 mL of tetrahydrofuran in a well-dried 300 mL four-necked eggplant flask (with a three-way cock, with a magnetic stirring bar), and cooled to -78 ° C. After adding 9.0 mL (14.3 mmol) of 1.59M hexane solution of n-butyllithium and reacting for 1 hour, 2 mL (25.8 mmol) of N, N-dimethylformamide (manufactured by Kanto Chemical Co., Ltd.) The mixture was warmed to room temperature and stirred for 63 hours. After cooling to 0 ° C., 15 mL of concentrated hydrochloric acid and 10 mL of water were added and stirred overnight, and the solvent was distilled off under reduced pressure. The residue was extracted with dichloromethane, washed with water and brine, and dried over anhydrous sodium sulfate. The solid was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (eluent; hexane / ethyl acetate = 49/1) to give compound 45. Obtained 806 mg (29%, light yellow solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 12.14 (s, 1H, OH), 9.92 (s, 1H, HC═O), 7.69-7.66 (m, 2H, Ar—H) 2.13-2.11 (m, 9H, Adamantyl), 1.81-1.79 (m, 6H, Adamantyl)

充分に乾燥した５０ｍＬ四口ナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物４５を０．８０６ｇ（２．４９ｍｍｏｌ）、２’‐ｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌ‐２‐ａｍｉｎｅ（ＷＯ２００９００５００３の記載に従い合成した。）を０．５１４ｇ（２．５８ｍｍｏｌ）、アンバーリスト１５（Ｈ）を０．１ｇ、無水硫酸ナトリウムを１．０４ｇ、トルエンを２６ｍＬ加え、還流下で８時間反応させた。この反応液から不溶物を濾過にて取り除いた後、溶媒を減圧下で留去し、ヘキサンとトルエンの混合溶媒から再結晶することにより化合物４６を０．８２３ｍｇ（６５％、黄色固体）得た。

In a well-dried 50 mL four-necked eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 0.806 g (2.49 mmol) of compound 45, 2′-methoxybiphenyl-2-amine (from WO2009005003) 0.514 g (2.58 mmol), Amberlyst 15 (H) 0.1 g, anhydrous sodium sulfate 1.04 g, and toluene 26 mL were added and reacted under reflux for 8 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from a mixed solvent of hexane and toluene gave 0.823 mg (65%, yellow solid) of Compound 46. .

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 14.37 (s, 1H, OH), 8.54 (s, 1H, HC = N), 7.48-7.32 (m, 7H, Ar—H) , 7.21 (dd, 1H, J = 7.4, 2.0 Hz, Ar-H), 7.02 (td, 1H, J = 7.4, 0.8 Hz, Ar-H), 6.94 (dd, 1H, J = 8.5,0.8Hz , Ar-H), 3.74 (s, 3H, OCH 3), 2.09 (bs, 9H, adamantyl), 1.78 (bs, 6H , Adamantyl)

充分に乾燥した５０ｍＬ四口ナスフラスコ（三方コック、磁気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を０．５ｍＬ（０．５ｍｍｏｌ）加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物４６の０．４１２ｇ（０．８２ｍｍｏｌ）をトルエン１０ｍＬに溶かして滴下した後、室温まで昇温させつつ２１時間反応させた。この反応液にペンタン１０ｍＬを加え析出させた後、析出物を濾取し、ペンタン（関東化学株式会社製）１０ｍＬで洗浄後、乾燥させることにより、化合物４７を０．２７６ｇ（収率５０％、橙色固体）得た。

Add 0.5 mL (0.5 mmol) of 1.0M toluene solution of titanium tetrachloride to a well-dried 50 mL four-necked eggplant flask (with three-way cock and magnetic stirrer), and cool to -78 ° C with a dry ice-acetone bath. did. To this, 0.412 g (0.82 mmol) of Compound 46 was dissolved and added dropwise in 10 mL of toluene, and then reacted for 21 hours while raising the temperature to room temperature. After adding 10 mL of pentane to the reaction solution to precipitate, the precipitate was collected by filtration, washed with 10 mL of pentane (manufactured by Kanto Chemical Co., Ltd.), and then dried to obtain 0.276 g of Compound 47 (yield 50%, An orange solid) was obtained.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.18 (s, 1H, HC = N), 7.76 (d, 1H, J = 2.2 Hz, Ar—H), 7.57 (d, 1H, J = 2.2Hz, Ar-H) , 7.53-7.18 (m, 8H, Ar-H), 4.41 (s, 3H, OCH 3), 2.22-2.19 (m, 9H, Adamantyl), 1.96-1.79 (m, 6H, Adamantyl)

[Synthesis Example 14]
(Synthesis of Compound 50)

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に化合物７を１．３０ｇ（７．２ｍｍｏｌ）、２‐ｂｒｏｍｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を１．０３ｇ（６ｍｍｏｌ）、酢酸パラジウムを０．０７ｇ（０．０３ｍｍｏｌ）、２‐Ｄｉｃｙｃｌｏｈｅｘｙｌｐｈｏｓｐｈｉｎｏ‐２’，６’‐ｄｉｍｅｔｈｏｘｙｂｉｐｈｅｎｙｌを０．０２５ｇ（０．０６ｍｍｏｌ）、リン酸カリウム一水和物４．１５ｇ（１８ｍｍｏｌ）加え、トルエン１８ｍＬに縣濁させ、１００℃で３時間反応させた。この反応液に水１０ｍＬを加え、トルエンで抽出後、有機層をＭｇＳＯ₄で乾燥させ、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９５／５）を用いて精製することにより化合物４８を０．３９０ｇ（２９％、薄黄色液体）を得た。

In a well-dried 100 mL three-necked eggplant flask (condenser, with three-way cock, with magnetic stirrer), 1.30 g (7.2 mmol) of compound 7 and 1.03 g (6 mmol) of 2-bromoaniline (manufactured by Tokyo Chemical Industry Co., Ltd.) ), 0.07 g (0.03 mmol) of palladium acetate, 0.025 g (0.06 mmol) of 2-Dicyclohexylphosphino-2 ′, 6′-dimethylbiphenyl, 4.15 g (18 mmol) of potassium phosphate monohydrate, The mixture was suspended in 18 mL of toluene and reacted at 100 ° C. for 3 hours. 10 mL of water was added to this reaction liquid, extracted with toluene, the organic layer was dried over MgSO ₄ , and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 95/5) to obtain 0.390 g (29%, light yellow liquid) of Compound 48.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.19-7.13 (m, 1H, Ar—H), 6.98-6.94 (m, 1H, Ar—H), 6.84-6. 76 (m, 3H, Ar- H), 6.66 (s, 1H, Ar-H), 3.71 (s, 3H, OCH 3), 3.45 (br, 2H, NH 2), 2. _{37 (s, 3H, CH 3} ), 2.05 (s, 3H, CH 3).

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物４８を０．３５８ｇ（１．５８ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｍｅｔｈｙｌｂｅｎｚａｌｄｅｈｙｄｅ０．４０６ｇ（１．５ｍｍｏｌ）、アンバーリスト１５（Ｈ）を４１ｍｇ加えトルエン３０ｍＬ加えた後、還流下で３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物４９を０．４０４ｇ（収率 ５６％、黄色固体）得た。

0.358 g (1.58 mmol) of 3-48 compound-2-hydroxy-5-methylbenzaldehyde 0.406 g in a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer) (1.5 mmol) and 41 mg of Amberlyst 15 (H) were added, 30 mL of toluene was added, and the mixture was reacted for 3 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.404 g of Compound 49 (yield 56%, yellow solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.2 (s, 1H, OH), 8.51 (s, 1H, N═CH), 7.48-7.24 (m, 4H, Ar—H) , 7.04-6.91 (m, 4H, Ar -H), 3.32 (s, 3H, OCH 3), 2.32 (s, 3H, CH 3), 2.30 (s, 3H, _{CH 3), 2.26 (s,} 3H, CH 3), 2.10 (s, 6H, adamantyl), 2.06 (s, 3H, adamantyl), 1.77 (s, 6H, adamantyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を０．５５ｍＬ（０．５５ｍｍｏｌ）、トルエンを１０ｍＬ加え−７８℃に冷却した。この混合液に化合物４９を０．２４０ｇ（０．５ｍｍｏｌ）をトルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１６時間反応させた。この反応液を減圧下で約５ｍＬまで濃縮した後、ヘキサン１５ｍＬを加え析出させ、析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物５０を０．１２３ｇ（収率 ３９％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 0.55 mL (0.55 mmol) of a toluene solution of TiCl ₄ (1.0 mmol / mL) and 10 mL of toluene were added and cooled to −78 ° C. In this mixed solution, 0.240 g (0.5 mmol) of compound 49 was dissolved in 5 mL of toluene and dropped, and then reacted for 16 hours while raising the temperature to room temperature. After concentrating the reaction solution to about 5 mL under reduced pressure, 15 mL of hexane was added for precipitation, and the precipitate was collected by filtration, washed with 20 mL of hexane, and dried to give 0.123 g of Compound 50 (yield 39%). A reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.13 (bs, 1H, N═CH), 7.46-6.91 (m, 8H, Ar—H), 4.27 (s, 3H, OCH ₃₎ ), 2.57 (s, 3H, CH ₃ ), 2.35 (s, 3H, CH ₃ ), 2.33 (s, 3H, CH ₃ ), 2.19 (bs, 6H, adamantyl), 2 .15 (bs, 3H, adamantyl), 1.92 (d, 3H, J = 12 Hz, adamantyl), 1.78 (d, 3H, J = 12 Hz, adamantyl)

[Synthesis Example 15]
(Synthesis of Compound 53)

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２−Ｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄ（東京化成工業株式会社製）を１．００ｇ（６．０ｍｍｏｌ）、２−Ｃｈｌｏｒｏ−４−ｍｅｔｈｙｌａｎｉｌｉｎｅ（東京化成工業株式会社製）を０．７０ｍＬ（５．７ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．００８ｇ（０．０２８ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）１．９７ｇ（６．２ｍｍｏｌ）加え、イソプロピルアルコール（関東化学株式会社製）４０ｍＬに溶解させ、８０℃で６時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９／１）を用いて精製することにより化合物５１を１．１２ｇ（８７％、淡褐色液体）得た。

1.00 g (6.0 mmol) of 2-Ethoxyphenylboronic acid (manufactured by Tokyo Chemical Industry Co., Ltd.), 2-Chloro-4-methylalanine in a 100 mL three-necked eggplant flask (condenser, with a three-way cock, with a magnetic stirrer) 0.70 mL (5.7 mmol) (manufactured by Tokyo Chemical Industry Co., Ltd.), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) -chloride (manufactured by Sigma Aldrich Japan Co., Ltd.) ), 0.008 g (0.028 mmol), 1.97 g (6.2 mmol) of barium hydroxide octahydrate (Wako Pure Chemical Industries, Ltd.) and 40 mL of isopropyl alcohol (Kanto Chemical Co., Ltd.) It was dissolved and reacted at 80 ° C. for 6 hours. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 9/1) to obtain 1.12 g (87%, light brown liquid) of Compound 51.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.34-7.24 (m, 2H, Ar—H), 7.06-6.94 (m, 4H, Ar—H), 6.69 (d, 1H, J = 8.1 Hz), 4.06 (q, 2H, J = 7.1 Hz, OCH ₂ ), 3.64 (bs, 2H, NH ₂ ), 2.28 (s, 3H, CH ₃ ) , 1.31 (t, 3H, J = 7.1 Hz, OCH ₂ CH ₃ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物５１を１．１２ｇ（４．９ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５−ｔｅｒｔ−ｂｕｔｙｌ−２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを１．４０ｇ（４．５ｍｍｏｌ）、アンバーリスト１５（Ｈ）を３３０ｍｇ、トルエン５０ｍＬを加えた後、還流下で２３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、メタノールから再結晶することにより化合物５２を１．８０ｇ（収率 ７７％、黄色固体）得た。

1.12 g (4.9 mmol) of compound 51 in a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 3-adamantyl-5-tert-butyl-2-hydroxydehydride After adding 1.40 g (4.5 mmol), Amberlyst 15 (H) 330 mg, and toluene 50 mL, the mixture was reacted under reflux for 23 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from methanol gave 1.80 g (yield 77%, yellow solid) of Compound 52.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.69 (s, 1H, OH), 8.49 (s, 1H, N═CH), 7.32-7.09 (m, 7H, Ar—H) , 6.89-6.89 (m, 2H, Ar -H), 4.02 (q, 2H, J = 6.9Hz, OCH 2), 2.41 (s, 3H, CH 3), 2. 11 (s, 6H, Adamantyl), 2.06 (s, 3H, Adamantyl), 1.77 (s, 6H, Adamantyl), 1.29 (s, 9H, tert-Butyl), 1.23 (t, 3H, J = 6.9 Hz, OCH ₂ CH ₃ )

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を１．０ｍＬ（１．０ｍｍｏｌ）、トルエン５ｍＬを加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物５２を０．４３８ｇ（０．８４ｍｍｏｌ）をトルエン１０ｍＬに溶かして滴下した後、室温まで昇温させつつ１６時間反応させた。この反応液を減圧下で約０．８ｍＬまで濃縮した後、ヘキサン１０ｍＬを加え析出させ、析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物５３を０．４１１ｇ（収率 ７０％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 1.0 mL (1.0 mmol) of 1.0 M toluene solution of titanium tetrachloride and 5 mL of toluene were added, and cooled to -78 ° C with a dry ice-acetone bath. . To this, 0.438 g (0.84 mmol) of Compound 52 was dissolved and added dropwise in 10 mL of toluene, and then reacted for 16 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 0.8 mL under reduced pressure, 10 mL of hexane was added for precipitation, the precipitate was collected by filtration, washed with 20 mL of hexane, and dried to give 0.411 g (yield). 70%, reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.14 (s, 1H, HC = N), 7.61 (d, 1H, J = 2.4 Hz, Ar—H), 7.45-7.23 ( m, 6H, Ar-H), 7.07 (d, 1H, J = 1.4 Hz, Ar-H), 6.96 (d, 1H, J = 8.1 Hz, Ar-H), 5.47. _{-5.40 (m, 1H, OCH 2} ), 4.87-4.81 (m, 1H, OCH 2), 2.42 (3H, s, CH 3), 2.28-2.16 (m , 9H, Adamantyl), 1.95-1.76 (m, 6H, Adamantyl), 1.28 (s, 9H, tert-Butyl), 0.99 (t, 3H, J = 7.2 Hz, OCH ₂ CH ₃₎

[Synthesis Example 16]
(Synthesis of Compound 55)

充分に乾燥した１００ｍLナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に２'−ｅｔｈｏｘｙｂｉｐｈｅｎｙｌ−２−ａｍｉｎｅを０．４４８ｇ（２．１ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐５‐ｔｅｒｔ−ｂｕｔｙｌ‐２‐ｈｙｄｒｏｘｙｂｅｎｚａｌｄｅｈｙｄｅを０．６２５ｇ（２．０ｍｍｏｌ）、アンバーリスト１５を６３ｍｇ加えトルエン２０ｍＬ加えた後、還流下で３時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物５４を０．５２５ｇ（収率 ５２％、黄色固体）得た。

A well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer) contains 2'-ethoxybiphenyl-2-amine in an amount of 0.448 g (2.1 mmol), 3-adamantyl-5-tert -Butyl-2-hydroxybenzaldehyde (0.625 g, 2.0 mmol), Amberlyst 63 (63 mg) and toluene (20 mL) were added, and the mixture was reacted under reflux for 3 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.525 g (yield 52%, yellow solid) of Compound 54.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.6 (s, 1H, OH), 8.50 (s, 1H, N═CH), 7.44-7.10 (m, 8H, Ar—H) , 6.99-6.89 (m, 2H, Ar -H), 4.01 (q, 2H, J = 6.8Hz, OCH 2), 2.11 (s, 6H, adamantyl), 2.07 (S, 3H, adamantyl), 1.77 (s, 6H, adamantyl), 1.29 (s, 9H, C (CH ₃ ) ₃ ), 1.26 (t, 3H, J = 6.8 Hz, CH ₃ )

充分に乾燥した１００ｍLシュレンクフラスコ（磁気攪拌子入り）にＴｉＣｌ₄のトルエン溶液（１．０ｍｍｏｌ／ｍＬ）を１．１ｍＬ（１．１ｍｍｏｌ）、トルエン２０ｍＬを加え−７８℃にドライアイス−メタノールバスにて冷却した。この混合液に化合物５４を０．５０８ｇ（１．０ｍｍｏｌ）トルエン５ｍＬに溶かし滴下した後、室温まで昇温させつつ１４時間反応させた。この反応液を減圧下で約５ｍＬまで濃縮した後に、ヘキサン１０ｍＬを加え析出させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物５５を０．４９３ｇ（収率 ７５％、赤紫色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), add 1.1 mL (1.1 mmol) of a TiCl ₄ toluene solution and 20 mL of toluene, and add to a dry ice-methanol bath at −78 ° C. And cooled. Compound 54 was dissolved in 0.508 g (1.0 mmol) of toluene (5 mL) and added dropwise to this mixed solution, and then reacted for 14 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 5 mL under reduced pressure, and 10 mL of hexane was added for precipitation. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.493 g of Compound 55 (yield 75%, red purple solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.17 (s, 1H, N═CH), 7.61 (s, 1H, Ar—H), 7.61-7.09 (m, 9H, Ar— H, 5.49-5.42 (m, 1H, OCH 2), 4.85-4.78 (m, 1H, OCH 2), 2.24-2.16 (m, 9H, adamantyl), 1 .93 (d, 3H, J = 12 Hz, adamantyl), 1.79 (d, 3H, J = 12 Hz, adamantyl), 1.28 (s, 9H, C (CH ₃ ) ₃ ), 0.95 (t , 3H, J = 7.0 Hz, CH ₃ )

[Synthesis Example 17]
(Synthesis of Compound 58)

充分に乾燥した２００ｍL三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に２‐ｍｅｔｈｏｘｙｐｈｅｎｙｌｂｏｒｏｎｉｃ ａｃｉｄを７．２ｇ（４７．１ｍｍｏｌ）、２−ｃｈｌｏｒｏ−６−ｍｅｔｈｙｌａｎｉｌｉｎｅを５．２０ｇ（３６．７ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅを５９．６ｍｇ（０．０９２ｍｍｏｌ）、水酸化バリウム八水和物を１２．８ｇ（４０．４ｍｍｏｌ）加え、イソプロピルアルコール７３ｍLに溶解させた後、８０℃で４時間反応させた。反応溶液を室温まで冷却した後、固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝９５／５）を用いて精製することにより化合物５６を６．２３ｇ（８０％、淡褐色液体）得た。

In a well-dried 200 mL three-necked eggplant flask (condenser, with a three-way cock, with magnetic stirrer), 7.2 g (47.1 mmol) of 2-methoxyphenylboronic acid and 5.20 g (36.7 mmol) of 2-chloro-6-methylalanine ), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) -chloride 59.6 mg (0.092 mmol), 12.8 g of barium hydroxide octahydrate (40 4 mmol) and dissolved in 73 mL of isopropyl alcohol, followed by reaction at 80 ° C. for 4 hours. After the reaction solution was cooled to room temperature, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 95/5) to obtain 6.23 g (80%, light brown liquid) of Compound 56.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.37-7.35 (m, 1H, Ar—H), 7.26-7.24 (m, 1H, Ar—H), 7.09-6. 97 (m, 4H, Ar- H), 6.77-6.75 (m, 1H, Ar-H), 3.79 (s, 3H, OCH 3), 3.59 (bs, 2H, NH 2 ), 2.28 (s, 3H, CH ₃ )

充分に乾燥した２００ｍＬ一口ナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物５６を１．１２ｇ（５．２５ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｍｅｔｈｙｌｂｅｎｚａｌｄｅｈｙｄeを１．３５ｇ（５．０ｍｍｏｌ）、アンバーリスト１５を１３５ｍｇ、トルエンを４０ｍＬ加えた後、還流下で６時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物５７を０．８３７ｇ（収率 ３６％、黄色固体）得た。

To a well-dried 200 mL one-necked eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer), 1.56 g (5.25 mmol) of compound 56, 3-adamantyl-2-hydroxy-5-methylbenzaldehyde 1.35 g (5.0 mmol), 135 mg of Amberlyst 15 and 40 mL of toluene were added, and the mixture was reacted for 6 hours under reflux. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.837 g (yield 36%, yellow solid) of Compound 57.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.6 (s, 1H, OH), 7.90 (s, 1H, C═NH), 7.26-7.15 (m, 6H, Ar—H) 7.03 (s, 1H, Ar-H), 6.94 (t, 1H, J = 7.3 Hz, Ar-H), 6.74 (d, 1H, J = 8.0 Hz, Ar-H) ), 3.67 (s, 3H, OCH ₃ ), 2.33 (s, 3H, CH ₃ ), 2.19 (s, 3H, CH ₃ ), 2.15 (bs, 6H, adamantyl), 2 .08 (bs, 3H, adamantyl), 1.79 (bs, 6H, adamantyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を０．５ｍＬ（０．５ｍｍｏｌ）、トルエンを１０ｍＬ加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物５７を０．２５６ｇ（０．５５ｍｍｏｌ）をトルエン５ｍＬに溶かしたものを滴下した後、室温まで昇温させつつ１５時間反応させた。反応液を３ｍＬまで減圧下で濃縮しヘキサン２０ｍＬを加えた後、析出物をろ取、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物５８を０．２９４ｇ（収率 ９５％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 0.5 mL (0.5 mmol) of a 1.0 M solution of titanium tetrachloride in toluene and 10 mL of toluene were added and cooled to −78 ° C. in a dry ice-acetone bath. . A solution obtained by dissolving 0.256 g (0.55 mmol) of Compound 57 in 5 mL of toluene was added dropwise thereto, and then reacted for 15 hours while raising the temperature to room temperature. The reaction solution was concentrated to 3 mL under reduced pressure, 20 mL of hexane was added, and the precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.294 g (yield 95%, reddish brown solid) of Compound 58. It was.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.90 (s, 1H, HC = N), 7.39-7.11 (m, 8H, Ar—H), 6.94 (s, 1H, Ar— H), 4.26 (s, 3H, OCH ₃ ), 2.45 (s, 3H, CH ₃ ), 2.28 (s, 3H, CH ₃ ), 2.19 (m, 9H, adamantyl), 1.96 (d, J = 11.5 Hz, 3H, adamantyl), 1.81 (d, J = 11.5 Hz, 3H, adamantyl)

[Synthesis Example 18]
(Synthesis of Compound 61)

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に化合物３３を１．０ｇ（４．４ｍｍｏｌ）、２−ｃｈｌｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を０．４６ｍＬ（４．４ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．０１３ｇ（０．０２２ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）１．５ｇ（４．６ｍｍｏｌ）加え、イソプロピルアルコール（関東化学株式会社製）３０ｍＬに溶解させ、８０℃で３時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝１０／１）を用いて精製することにより化合物５９を１．１８ｇ（９８％、淡褐色液体）得た。

In a well-dried 100 mL three-necked eggplant flask (condenser, with a three-way cock, with a magnetic stirrer), 1.0 g (4.4 mmol) of compound 33 and 0.46 mL (4) of 2-chloroaniline (manufactured by Tokyo Chemical Industry Co., Ltd.) .4 mmol), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) -chloride (manufactured by Sigma Aldrich Japan Co., Ltd.), 0.013 g (0.022 mmol), barium hydroxide 1.5 g (4.6 mmol) of octahydrate (Wako Pure Chemical Industries, Ltd.) was added, dissolved in 30 mL of isopropyl alcohol (Kanto Chemical Co., Ltd.), and reacted at 80 ° C. for 3 hours. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 10/1) to obtain 1.18 g (98%, light brown liquid) of Compound 59.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.61-7.52 (m, 4H, Ar—H), 7.41 (m, 2H, Ar—H), 7.33-7.14 (m, 3H, Ar-H), 7.07 (d, J = 8.6 Hz, 1H, Ar-H), 6.88-6.78 (m, 2H, Ar-H),
3.85 (s, 3H, OCH ₃ ), 3.73 (bs, 2H, NH ₂ )

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物５９を０．６０ｇ（２．２ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｐｈｅｎｙｌｂｅｎｚａｌｄｅｈｙｄｅ０．７２ｇ（２．２ｍｍｏｌ）、エタノール１５ｍＬを加えた後、還流下で６時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物６０を１．１７ｇ（収率 ９６％、黄色固体）得た。

0.60 g (2.2 mmol), 3-adamantyl-2-hydroxy-5-phenylbenzaldehyde 0.72 g in a well-dried 100 mL eggplant flask (three-way cock, Dean-Stark tube, with Dimroth, with magnetic stirrer) (2.2 mmol) and ethanol (15 mL) were added, followed by reaction under reflux for 6 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 1.17 g of Compound 60 (yield 96%, yellow solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.8 (s, 1H, OH), 8.62 (s, 1H, N═CH), 7.61-7.27 (m, 18H, Ar—H) 7.03 (d, J = 8.6 Hz, 1H, Ar—H), 3.82 (s, 3H, OCH ₃ ), 2.14 (m, 6H, adamantyl), 2.06 (m, 3H) , Adamantyl), 1.76 (s, 6H, adamantyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を０．３ｍＬ（０．３ｍｍｏｌ）、ヘキサンを２０ｍＬ加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物６０を０．１９５ｇ（０．３３ｍｍｏｌ）をトルエン１ｍＬ／ヘキサン１０ｍＬに溶かしたものを滴下した後、室温まで昇温させつつ２時間反応させた。析出物をろ取し、ヘキサン２０ｍＬで洗浄後、乾燥させることにより、化合物６１を０．１７０ｇ（収率 ８６％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 0.3 mL (0.3 mmol) of 1.0 M toluene solution of titanium tetrachloride and 20 mL of hexane were added, and cooled to −78 ° C. with a dry ice-acetone bath. . A solution prepared by dissolving 0.195 g (0.33 mmol) of Compound 60 in 1 mL of toluene / 10 mL of hexane was added dropwise thereto, and then reacted for 2 hours while raising the temperature to room temperature. The precipitate was collected by filtration, washed with 20 mL of hexane, and dried to obtain 0.170 g of Compound 61 (yield 86%, reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.28 (s, 1H, HC = N), 7.80 (d, J = 2.3 Hz, 1H, Ar—H), 7.63-7.30 ( m, 17H, Ar-H) , 7.19 (m, 1H, Ar-H), 4.47 (s, 3H, OCH 3), 2.28 (m, 6H, adamantyl), 2.19 (m , 3H, adamantyl), 1.95 (d, J = 13.2 Hz, 3H, adamantyl), 1.81 (d, J = 13.2 Hz, 3H, adamantyl)

[Synthesis Example 19]
(Synthesis of Compound 64)

充分に乾燥した１００ｍＬ三口ナスフラスコ（コンデンサー、三方コック付、磁気攪拌子入り）に化合物３８を１．０ｇ（３．７ｍｍｏｌ）、２−ｃｈｌｏｒｏａｎｉｌｉｎｅ（東京化成工業株式会社製）を０．３９ｍＬ（３．９ｍｍｏｌ）、１，３−ｂｉｓ−（２，６−ｄｉｉｓｏｐｒｏｐｙｌｐｈｅｎｙｌ）ｉｍｉｄａｚｏｌｉｕｍ−（ａｌｌｙｌ）−ｐａｌｌａｄｉｕｍ（ＩＩ）−ｃｈｌｏｒｉｄｅ（シグマ アルドリッチ ジャパン 株式会社製）を０．０１１ｇ（０．０１９ｍｍｏｌ）、水酸化バリウム八水和物（和光純薬工業株式会社製）１．２ｇ（３．９ｍｍｏｌ）加え、イソプロピルアルコール（関東化学株式会社製）３０ｍＬに溶解させ、８０℃で３時間反応させた。反応後固体残さをろ過によって取り除き、溶媒を減圧下で留去することにより粗生成物を得た。粗生成物をシリカゲルカラムクロマトグラフ（溶離液；ヘキサン／酢酸エチル＝１０／１）を用いて精製することにより化合物６２を０．９１ｇ（７７％、淡褐色液体）得た。

In a well-dried 100 mL three-necked eggplant flask (condenser, with a three-way cock, with a magnetic stirrer), 1.0 g (3.7 mmol) of compound 38 and 0.39 mL (3) of 2-chloroanline (manufactured by Tokyo Chemical Industry Co., Ltd.) .9 mmol), 1,3-bis- (2,6-diisopropylphenyl) imidazolium- (allyl) -palladium (II) -chloride (manufactured by Sigma Aldrich Japan Co., Ltd.), 0.011 g (0.019 mmol), barium hydroxide 1.2 g (3.9 mmol) of octahydrate (manufactured by Wako Pure Chemical Industries, Ltd.) was added, dissolved in 30 mL of isopropyl alcohol (manufactured by Kanto Chemical Co., Ltd.) and reacted at 80 ° C. for 3 hours. After the reaction, the solid residue was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The crude product was purified using silica gel column chromatography (eluent: hexane / ethyl acetate = 10/1) to obtain 0.91 g (77%, light brown liquid) of Compound 62.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 7.27-7.06 (m, 9H, Ar—H), 6.90-6.73 (m, 3H, Ar—H), 3.78 (s, 3H, OCH ₃ ), 3.68 (bs, 2H, NH ₂ ), 1.68 (s, 6H, cumyl)

充分に乾燥した１００ｍＬナスフラスコ（三方コック、ディーン・スターク管、ジムロート付、磁気攪拌子入り）に化合物６２を０．４０ｇ（１．２８ｍｍｏｌ）、３‐ａｄａｍａｎｔｙｌ‐２‐ｈｙｄｒｏｘｙ‐５‐ｐｈｅｎｙｌｂｅｎｚａｌｄｅｈｙｄｅ０．４２ｇ（１．２８ｍｍｏｌ）、エタノール１５ｍＬを加えた後、還流下で５時間反応させた。この反応液から不溶物をろ過にて取り除いた後、溶媒を減圧下で留去し、エタノールから再結晶することにより化合物６３を０．６３９ｇ（収率 ６７％、橙色固体）得た。

In a well-dried 100 mL eggplant flask (three-way cock, Dean Stark tube, with Dimroth, with magnetic stirrer), 0.40 g (1.28 mmol) of compound 62, 3-adamantyl-2-hydroxy-5-phenylbenzaldehyde 0.42 g (1.28 mmol) and ethanol (15 mL) were added, followed by reaction under reflux for 5 hours. After removing insolubles from the reaction solution by filtration, the solvent was distilled off under reduced pressure, and recrystallization from ethanol gave 0.639 g (yield 67%, orange solid) of Compound 63.

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 13.7 (s, 1H, OH), 8.54 (d, J = 2.0 Hz, 1H, N = CH), 7.57-7.30 (m, 10H), 7.23-7.08 (m, 8H , Ar-H), 6.84 (d, J = 9.2Hz, 1H, Ar-H), 3.70 (s, 3H, OCH 3) 2.18 (s, 6H, adamantyl), 2.08 (s, 3H, adamantyl), 1.78 (s, 6H, adamantyl), 1.70 (s, 6H, cumyl)

充分に乾燥した１００ｍＬシュレンクフラスコ（磁気攪拌子入り）に四塩化チタンの１．０Ｍトルエン溶液を０．８ｍＬ（０．８ｍｍｏｌ）、トルエンを１５ｍL加え、ドライアイス−アセトンバスで−７８℃に冷却した。これに、化合物６３を０．５５６ｇ（０．８８ｍｍｏｌ）をトルエン１０ｍＬに溶かしたものを滴下した後、室温まで昇温させつつ１６時間反応させた。反応液を３ｍＬ程度まで濃縮した後ヘキサン２０ｍＬを加え、沈殿物をろ取、乾燥させることにより、化合物６４を０．５５５ｇ（収率 ８７％、赤褐色固体）得た。

To a well-dried 100 mL Schlenk flask (with magnetic stirrer), 0.8 mL (0.8 mmol) of a 1.0 M toluene solution of titanium tetrachloride and 15 mL of toluene were added, and cooled to −78 ° C. in a dry ice-acetone bath. . A solution prepared by dissolving 0.556 g (0.88 mmol) of Compound 63 in 10 mL of toluene was added dropwise thereto, and then reacted for 16 hours while raising the temperature to room temperature. The reaction solution was concentrated to about 3 mL, 20 mL of hexane was added, and the precipitate was collected by filtration and dried to obtain 0.555 g of Compound 64 (yield 87%, reddish brown solid).

The result of analyzing the obtained product was as follows.
¹ H NMR (δ, CDCl ₃ ): 8.20 (s, 1H, HC = N), 7.81 (d, J = 2.3 Hz, 1H, Ar—H), 7.53-7.04 ( m, 18H, Ar-H) , 4.39 (s, 3H, OCH 3), 2.28-2.18 (m, 9H, adamantyl), 1.95 (d, J = 10.9Hz, 3H, adamantyl), 1.81 (d, J = 10.9 Hz, 3H, adamantyl), 1.64 (s, 6H, cumyl)

[Example 1]
To an autoclave with an internal volume of 100 mL sufficiently purged with nitrogen, 28 mL of toluene was added, and then 0.5 mmol of methylaluminoxane (Tosoh Finechem MMAO-3A, 10 wt% hexane solution) was added in terms of aluminum atoms. Subsequently, 0.1 μmol of the compound 3 (1 mM toluene solution) was added, and the reaction was started by pressurizing with ethylene (0.8 MPa-G). The reaction was stopped at 25 ° C. for 60 minutes while supplying ethylene at the same pressure, and then the reaction was stopped by adding a small amount of isopropanol. After completion of the reaction, the reaction solution is washed with 0.1 N hydrochloric acid and pure water, and a low-boiling component (10 or less carbon atoms) is separated from the high-boiling component and polyethylene using a liquid nitrogen trap under reduced pressure. Analysis was performed using chromatography. The selectivity of 1-hexene among the products was 85.3%. As other products, the selectivity of decenes was 11.0%, the selectivity of polyethylene was 3.7%, and the catalytic activity calculated from the total amount of these products was 28.6 kg-product / (mmol-Ti -H). In addition, the same reaction as described above was performed even at a reaction temperature of 40 ° C. The results are shown in Table 1.

[Examples 2-5, 7-10]
The reaction was carried out at reaction temperatures of 25 ° C. and 40 ° C. in the same manner as in Example 1 except that compounds 6, 10, 13, 16, 23, 26, 29, and 32 were used instead of compound 3. The results are shown in Table 1.

[Example 6]
The reaction was performed in a reaction time of 60 minutes and 10 minutes in the same manner as in Example 1 except that Compound 19 was used instead of Compound 3. The results are shown in Table 1.

[Examples 11 and 12]
The reaction was performed in the same manner as in Example 1 except that the compounds 36 and 41 were used in place of the compound 3 and the reaction time was 10 minutes. The results are shown in Table 1.

[Comparative Examples 1, 2, 4, 5]
The reaction was carried out at reaction temperatures of 25 ° C. and 40 ° C. in the same manner as in Example 1 except that compounds 47, 50, 53, and 55 were used instead of compound 3, respectively. The results are shown in Table 1.

[Comparative Example 3]
The reaction temperature was 25 in the same manner as in Example 1 except that 0.25 μmol of Compound 9 (Compound 65 below) (1 mM toluene solution) described in WO2009 / 005003 pamphlet [0225] was used instead of Compound 3. Reactions were carried out at 0 ° C and 40 ° C. Similarly, the reaction was conducted at a reaction temperature of 25 ° C. and a reaction time of 10 minutes. The results are shown in Table 1.

[Comparative Examples 6, 7, 8]
The reaction was performed in the same manner as in Example 1 except that the compounds 58, 61, and 64 were used in place of the compound 3 and the reaction time was 10 minutes. The results are shown in Table 1.

［比較例９］
充分に窒素置換した内容積５００ｍＬのオートクレーブにｎ−へプタン１４４ｍＬを入れ、続いて、メチルアルミノキサン（東ソー・ファインケムＭＭＡＯ−３Ａ，１Ｍヘキサン溶液）をアルミニウム原子換算で１．０ｍｍｏｌ加えた。引き続き、上記化合物６５（１．０ｍＭトルエン溶液）を０．５μｍｏｌ加え、エチレン（３．５ＭＰａ−Ｇ）、水素（０．１ＭＰａ−Ｇ）で加圧して反応を開始した。同圧力でエチレンを供給しながら５０℃で６０分間反応させた後、少量のメタノールを添加することにより反応を停止した。反応終了後、０．１規定塩酸水および純水で反応液を洗浄し、減圧下に液体窒素トラップを用いて低沸点成分（炭素原子数１０以下）を高沸点成分およびポリエチレンから分離し、ガスクロマトグラフィーを用いて分析を行った。生成物のうち１−ヘキセンの選択率は９４．６％であった。その他の生成物としてデセン類の選択率は４．９％、ポリエチレンの選択率は０．５％であり、これらの生成物量合計から算出した触媒活性は６７ｋｇ−生成物／（ｍｍｏｌ−Ｔｉ・ｈ）であった。

[Comparative Example 9]
144 mL of n-heptane was put into an autoclave having an internal volume of 500 mL that was sufficiently purged with nitrogen, and then 1.0 mmol of methylaluminoxane (Tosoh Finechem MMAO-3A, 1M hexane solution) was added in terms of aluminum atom. Subsequently, 0.5 μmol of the compound 65 (1.0 mM toluene solution) was added, and the reaction was started by pressurizing with ethylene (3.5 MPa-G) and hydrogen (0.1 MPa-G). After reacting at 50 ° C. for 60 minutes while supplying ethylene at the same pressure, the reaction was stopped by adding a small amount of methanol. After completion of the reaction, the reaction solution is washed with 0.1 N hydrochloric acid and pure water, and a low-boiling component (10 or less carbon atoms) is separated from the high-boiling component and polyethylene using a liquid nitrogen trap under reduced pressure. Analysis was performed using chromatography. Among the products, the selectivity of 1-hexene was 94.6%. As other products, the selectivity of decenes was 4.9%, and the selectivity of polyethylene was 0.5%. The catalytic activity calculated from the total amount of these products was 67 kg-product / (mmol-Ti · h). )Met.

［実施例１３、比較例１０］
化合物３に代えて化合物６，６５をそれぞれ用いて、反応温度は２５℃のみとし、反応時間を１０分とした以外は実施例１と同様にして反応を行った。このときの触媒活性は化合物６５が３６．６ｋｇ−生成物／（ｍｍｏｌ−Ｔｉ・ｈ）であったのに対し、化合物６では１０６．２ｋｇ−生成物／（ｍｍｏｌ−Ｔｉ・ｈ）とおよそ３倍の反応性を示した。これは前述の計算によって得られた活性化エネルギーからの予測とよく一致している。

[Example 13, Comparative Example 10]
The reaction was carried out in the same manner as in Example 1 except that the compounds 6 and 65 were used in place of the compound 3, the reaction temperature was only 25 ° C., and the reaction time was 10 minutes. In this case, the catalytic activity of Compound 65 was 36.6 kg-product / (mmol-Ti · h), whereas Compound 6 was 106.2 kg-product / (mmol-Ti · h), approximately 3 Double reactivity was shown. This is in good agreement with the prediction from the activation energy obtained by the above calculation.

  From the results of the above Examples and Comparative Examples, it became clear that the olefin multimerization reaction using the transition metal compound according to the present invention shows a higher activity than the case of using a conventionally known transition metal compound. . This is because, as described above, the introduction of a substituent at a specific position of the phenoxyimine ligand of the transition metal compound represented by the general formula (1) according to the present invention reduces the activation energy of the reaction. It can be assumed that the reaction rate is significantly increased at the initial stage of the reaction.

  When the olefin multimerization reaction is carried out using the transition metal compound according to the present invention, an olefin multimer can be obtained with a higher catalytic activity than before, which is extremely valuable industrially.

Claims (10)

A transition metal compound represented by the following general formula (1).

[In General Formula (1), M represents an atom of Groups 4-6 of the periodic table,
R ^{1 to} R ⁵ and R ¹⁴ may be the same or different from each other, and are atoms or groups selected from a hydrogen atom, a halogen atom, a hydrocarbon group, a silicon-containing group, an oxygen-containing group, and a nitrogen-containing group,
R ⁶ to R ¹³ may be the same or different from each other, a hydrogen atom, a halogen atom, a hydrocarbon group, an atom or radical selected from a silicon-containing group, an oxygen-containing group and a nitrogen-containing group, R ⁶ ~ At least one of R ¹³ is a halogen atom;
Two adjacent groups out of the groups represented by R ^{1 to} R ¹⁴ may be bonded to form a ring together with the carbon atoms to which they are bonded.
n represents the valence of M.
X represents a group selected from a hydrogen atom, a halogen atom, a hydrocarbon group, an oxygen-containing group and a nitrogen-containing group, and a plurality of atoms or groups represented by X may be the same or different from each other, and are represented by X A plurality of groups may be bonded to each other, and a plurality of groups represented by X may be bonded to each other to form a ring. ] In the said General formula (1), at least one is a halogen atom among R < ⁶ >, R < ⁸ > or R < ¹² >, The transition metal compound of Claim 1 characterized by the above-mentioned. The transition metal compound according to claim 2, wherein at least one of R ⁶ , R ^{8, and} R ^{12 in} the general formula (1) is a fluorine atom. In said general formula (1), R < ¹ > is a C2-C12 alkyl group, The transition metal compound of Claim 2 or 3 characterized by the above-mentioned. In the general formula (1), R ³ or at least one transition metal compound according to any one of claims 2-4, characterized in that a hydrocarbon group having 3 to 30 carbon atoms of R ¹¹ . In the general formula (1), a transition metal compound according to any one of claims 1-3, wherein R ² is a tertiary alkyl group or a hydrocarbon group-substituted tertiary silyl group.   In said general formula (1), M is a titanium atom, The transition metal compound of any one of Claims 1-6 characterized by the above-mentioned. An olefin multimerization catalyst comprising the following component (A) and component (B):
(A) Transition metal compound according to any one of claims 1 to 7 (B) (B-1) Organometallic compound (B-2) Organoaluminum oxy compound, and (B-3) Transition metal compound ( At least one compound selected from the group consisting of compounds that react with A) to form ion pairs. The olefin multimerization catalyst according to claim 8, further comprising the following component (C).
Component (C); a carrier for supporting at least one compound selected from component (A) and component (B).   A method for producing an olefin multimer, wherein the olefin is multimerized using the olefin multimerization catalyst according to claim 8 or 9.

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