JP2000169407A - Production of 3-butene-1-ol derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject derivative useful as an intermediate for a medicine in excellent selectivity in a high yield by using a carbonyl-ene reaction in the presence of an inexpensive and readily obtainable trifluoroborane compound and an aluminosilicate. SOLUTION: A compound of formula [R1 is a 1-6C alkyl, a 3-6C cycloalkyl, a (substituted) 6-10C aryl or the like] is reacted with a compound of formula II (R2 is H, a 1-6C alkoxycarbonyl, a 1-6C alkyl, a 1-6C halogenated alkyl or the like) in the presence of a trifluoroborane compound (preferably trifluoroborane 1-4C alkyl ether complex, etc.), and an aluminosilicate (preferably synthetic zeolite, etc.), to give a compound of formula III such as 3-(3,4- dichlorophenyl)-3-butene-1-ol, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to 3-butene-1-use useful as an intermediate for functional substances such as pharmaceuticals, agricultural chemicals, and liquid crystals.
The present invention relates to a method for producing an all derivative.

[0002]

2. Description of the Related Art As a method for synthesizing a 3-buten-1-ol derivative, a carbonyl-ene reaction of a 1,1-disubstituted olefin with an aldehyde in the presence of a protonic acid, a Lewis acid or montmorillonite is known. [Tet
rahedron Lett. , 21 , 1815 (19
80), Synth. Commun. , 11 , 299
(1981), J. Mol. Am. Chem. Soc. , 71 ,
2860 (1949); Org. Chem. , 3
3 , 1156 (1968); Org. Chem. ,
36 , 1755 (1971); Chem. So
c. , Perkin Trans. 1,169 (19
97)]. However, these methods have disadvantages such as the use of alkyl aluminums which are dangerous to handle and require complicated post-treatment, and the use of highly toxic tin chlorides. There is no method that can be obtained in high yield, and it cannot be said that it is an industrially suitable method.

[0003]

SUMMARY OF THE INVENTION The present inventors have made intensive studies to solve these problems and establish an industrial process for producing 3-buten-1-ol compounds. Using a carbonyl-ene reaction characterized in that it is reacted in the presence of an inexpensive and readily available trifluoroborane compound and an aluminosilicate, so that the 3-buten-1-ol derivative has a selectivity and The present inventors have found that they can be obtained in good yield, and have completed the present invention.

[0004]

According to the present invention, there is provided a compound represented by the general formula:

[0005]

Embedded image [Wherein, R ¹ represents a linear or branched alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, or a carbon number which may have a substituent. An aryl group having 6 to 10 carbon atoms (the substituent may be a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms) An alkyl group having 1 to 6 carbon atoms, a linear or branched halogenated alkyl group having 1 to 6 carbon atoms,
Linear or branched aliphatic acyl group having
A linear or branched aliphatic acyloxy group having 1 to 6 carbon atoms, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group or a cyano group; Represents a group. ). And a compound represented by the general formula:

[0006]

Embedded image (Wherein R ² represents a hydrogen atom, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms) A linear or branched halogenated alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms) is a trifluoroborane compound And reacting in the presence of an aluminosilicate, a general formula

[0007]

Embedded image (Wherein, R ¹ and R ² have the same meanings as described above.)
This is a method for producing a 3-buten-1-ol derivative represented by the formula:

In the compound (1), the linear or branched alkyl group having 1 to 6 carbon atoms of R ¹ is, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl , T-butyl, pentyl, isopentyl, 2-methyl-2-butyl, 3-
A methylbutyl, neopentyl, hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl or 2,3-dimethylbutyl group, preferably A branched alkyl group having 3 to 5 carbon atoms, more preferably t-butyl or 2-methyl-2-
A butyl group, particularly preferably a t-butyl group.

The cycloalkyl group having 3 to 6 carbon atoms for R ¹ is, for example, cyclopropyl, cyclobutyl,
A cyclopentyl or cyclohexyl group, preferably a cycloalkyl group having 5 to 6 carbon atoms,
More preferably, it is a cyclohexyl group. The unsubstituted aryl group in the aryl group having 6 to 10 carbon atoms which may have a substituent for R ¹ is, for example, phenyl,
-Naphthyl or 2-naphthyl, preferably phenyl.

The number of substituents of the aryl group having a substituent is preferably 1 to 3, more preferably 1 or 2.
It is.

In the substitution of the aryl group: 1) The linear or branched alkyl group having 1 to 6 carbon atoms is, for example, the same group as described above, and preferably has the same number of carbon atoms. It is a linear or branched alkyl group having 1 to 3 groups, more preferably a methyl group.

2) The straight-chain or branched alkoxy group having 1 to 6 carbon atoms is, for example, the above-mentioned "straight-chain or branched alkyl group having 1 to 6 carbon atoms". Is a group bonded to an oxygen atom, and preferably has 1 carbon atom
It is a linear or branched alkoxy group having from 1 to 3 groups, more preferably a methoxy group.

3) The straight-chain or branched alkyl halide group having 1 to 6 carbon atoms is the above-mentioned "straight-chain or branched alkyl group having 1 to 6 carbon atoms". Is a group in which 1 to 5 halogen atoms are substituted, for example, fluoromethyl, chloromethyl, bromomethyl,
Iodomethyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2-iodoethyl, 2,2-dibromoethyl, 2,2,2-trifluoro An ethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl or pentafluoroethyl group, preferably a linear or branched group having 1 to 3 carbon atoms A group in which 1 to 3 fluorine or chlorine atoms are substituted on a chain alkyl group, more preferably a trifluoromethyl group.

4) A linear or branched aliphatic acyl group having 1 to 6 carbon atoms includes, for example, formyl,
It is an acetyl, propionyl, butyryl, isobutyryl, valeryl or hexanoyl group, preferably an aliphatic acyl group having 1 to 3 carbon atoms, more preferably an acetyl group.

5) A linear or branched aliphatic acyloxy group having 1 to 6 carbon atoms is, for example, formyloxy, acetoxy, propionyloxy, butyryloxy, or t-butyryloxy, valeryloxy or hexanoyloxy And an aliphatic acyloxy group having 1 to 3 carbon atoms, and more preferably an acetoxy group.

6) The straight-chain or branched alkoxycarbonyl group having 1 to 6 carbon atoms is, for example, the above-mentioned "straight-chain or branched alkoxy group having 1 to 6 carbon atoms". Is a group bonded to a carbonyl group,
It is preferably a linear or branched alkoxycarbonyl group having 1 to 3 carbon atoms, more preferably
It is a methoxycarbonyl group.

7) The halogen atom is, for example, a fluorine, chlorine, bromine or iodine atom, preferably a fluorine or chlorine atom.

A) The substituent of the aryl group is preferably a halogenated alkyl group having 1 to 6 carbon atoms,
Aliphatic acyl group having 1 to 6 carbon atoms, aliphatic acyloxy group having 1 to 6 carbon atoms, alkoxycarbonyl group having 1 to 6 carbon atoms, halogen atom, nitro group or cyano group, more preferably A linear or branched alkyl group having 1 to 3 carbon atoms substituted with 1 to 3 fluorine or chlorine atoms; an aliphatic acyl group having 1 to 3 carbon atoms; An aliphatic acyloxy group having 1 to 3 carbon atoms, a linear or branched alkoxycarbonyl group having 1 to 3 carbon atoms, a halogen atom, a nitro group or a cyano group; A methyl group, an acetyl group, an acetoxy group, a methoxycarbonyl group, an ethoxycarbonyl group, a halogen atom, a nitro group or a cyano group; An atom, particularly preferably a fluorine or chlorine atom.

In the compound having the general formula (1), preferably, a-1) R ¹ is a branched alkyl group having 3 to 5 carbon atoms, or a cycloalkyl group having 5 to 6 carbon atoms. An aryl group having 6 to 10 carbon atoms which may have a substituent (the substituent is a linear or branched halogenated alkyl group having 1 to 6 carbon atoms, Linear or branched aliphatic acyl group having 1 to 6 carbon atoms, linear or branched aliphatic acyloxy group having 1 to 6 carbon atoms, and linear or branched aliphatic acyloxy group having 1 to 6 carbon atoms. A chain or branched alkoxycarbonyl group,
It is a halogen atom, a nitro group or a cyano group. A-2) an aryl group having 6 to 10 carbon atoms in which R ¹ may have a substituent (the substituent is a group having 1 to 3 carbon atoms)
Straight or branched alkyl group having 1 to 3 fluorine or chlorine atoms, aliphatic acyl group having 1 to 3 carbon atoms, 1 to 3 carbon atoms An aliphatic acyloxy group, a linear or branched alkoxycarbonyl group having 1 to 3 carbon atoms, a halogen atom, a nitro group or a cyano group. And even more preferably a-3) a phenyl group in which R ¹ may have a substituent, wherein the substituent comprises a trifluoromethyl group, an acetyl group, a halogen atom, a nitro group and a cyano group And particularly preferably a-4) R ¹ has 1 or 2 substituents selected from the group consisting of fluorine and chlorine atoms. Is a phenyl group which may be substituted. In compound (2), R ² is a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms, The linear or branched halogenated alkyl group having 1 to 6 carbon atoms and the cycloalkyl group having 3 to 6 carbon atoms have the same meanings as the corresponding groups of R ¹ described above. , Preferably having 1 carbon atom
An alkoxycarbonyl group having 1 to 3 carbon atoms, an alkyl group having 1 to 3 carbon atoms, a group in which an alkyl group having 1 to 3 carbon atoms is substituted with 1 to 3 fluorine or chlorine atoms, or 5 to 6 carbon atoms And more preferably a methoxycarbonyl, ethoxycarbonyl, methyl, ethyl, propyl or trichloromethyl group.

In the compound having the general formula (2), preferably, b-1) R ² is a hydrogen atom, an alkoxycarbonyl group having 1 to 3 carbon atoms, an alkyl group having 1 to 3 carbon atoms, A group in which 1 to 3 fluorine or chlorine atoms are substituted for an alkyl group having 1 to 3 atoms or 5 carbon atoms
More preferably b-2) R ² is a hydrogen atom, methoxycarbonyl, ethoxycarbonyl, methyl, ethyl, propyl or trichloromethyl group, particularly preferably b-3 ) R ² is a hydrogen atom.

A preferred compound in the compound (3) is R
¹ is a group of a-1) in the compound (1), and R ²
Is a group as defined above for the compound (2), and more preferred compounds are those wherein R ¹ is a-2) for the compound (1)
A group, a b-1) of the groups R ² are the compound (2), even more preferred compounds is a group of R ¹ is the compound (1) a-3 in), R ² Is a group of b-2) of the compound (2), and a particularly preferred compound is R
¹ is a group of a-4) in the compound (1), and R ²
Is a group of b-3) of the compound (2).

[0022]

BEST MODE FOR CARRYING OUT THE INVENTION The amount of the aldehyde of the compound (2) used is 1.0 to 10.0 equivalents, preferably 1.0 to 2.0 equivalents, relative to the compound (1). is there.

The trifluoroborane compound used is
For example, trifluoroborane; a trifluoroborane-alkyl ether complex having 1 to 4 carbon atoms such as a trifluoroborane-methyl ether complex, a trifluoroborane-ethyl ether complex, and a trifluoroborane-n-butyl ether complex; Trifluoroborane, such as a run-methyl sulfide complex, having 1 to 4 carbon atoms
Or a trifluoroborane / tetrahydrofuran complex, preferably a trifluoroborane / alkyl ether complex having 1 to 4 carbon atoms, and more preferably a trifluoroborane / ethyl ether complex. is there. The amount of the trifluoroborane compound used is 1.0 to 10.0 with respect to the compound (1).
Equivalent, preferably 1.0 to 2.0 equivalents.

The aluminosilicate used is, for example,
Natural zeolites, synthetic zeolites such as 3A molecular sieves, 4A molecular sieves, 5A molecular sieves, X molecular sieves or Y molecular sieves, or montmorillonite are preferred, preferably 3A molecular sieves, more preferably 3A molecular sieves, 4A It is a molecular sieve, 5A molecular sieve, X molecular sieve or Y molecular sieve, particularly preferably X molecular sieve, Y molecular sieve or 4A molecular sieve.

The amount of the aluminosilicate used is 0.1 to 10.0 wt, preferably 0.5 to 2.0 wt, relative to compound (1).

In the present reaction, the reaction temperature depends on the type and amount of the aluminosilicate used, but it is -50 to 1
00 ° C., preferably -20 to 10 ° C.

The reaction time is 1.0 to 10.0 hours, preferably 1.0 to 4.0 hours, depending on the type and amount of the aluminosilicate used.

This reaction is preferably carried out in the presence of a solvent. The solvent used is not particularly limited as long as it does not affect the reaction, and examples thereof include aromatic hydrocarbons such as benzene, toluene and xylene. Or nitriles such as acetonitrile; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane;
It is preferably a halogenated hydrocarbon, and more preferably dichloromethane.

After completion of the reaction, the target compound is prepared according to a conventional method.
Collected from the reaction mixture. For example, the reaction mixture is appropriately neutralized, and after removing insoluble matter by filtration, the organic layer is washed with a saturated saline solution or the like, dried over anhydrous magnesium sulfate or the like, and then obtained by distilling off the solvent. . The obtained target compound can be purified as necessary by a conventional method, for example, column chromatography, distillation, recrystallization, or the like.

The starting compounds (1) and (2) used in the present invention are known compounds or are easily produced by known methods. [For example, J. Am. Chem. So
c. , 81 , 228 (1959); Org. Che
m. , 47 , 4572 (1982), Bull. So
c. Chim. Fr. , 1327 (1904)] In the compound of the present invention, (3) is a compound represented by the following Method A (Japanese Unexamined Patent Application Publication No.
Compound (A) useful as a tachykinin antagonist by the same method as described in JP-A-235275), and is useful as a synthetic intermediate.

[0031]

Embedded image In the above formula, R ¹ and R ² have the same meanings as described above,
R ³ is an alkyl group having 1 to 4 carbon atoms, 1 carbon atom
X represents a phenyl group which may have 1 to 3 substituents selected from the group consisting of an alkoxy group having 4 to 4 halogen atoms and X represents a halogen atom (preferably a chlorine atom); Ts represents a t-butyldimethylsilyl group, Ts represents a toluenesulfonyl group, and Boc represents t-
Shows a butoxycarbonyl group.

In the first step, the hydroxyl group of compound (3) of the present invention is protected to give compound (4). In the step of reacting compound (3) with a hydroxyl-protecting reagent in an inert solvent in the presence of a base. This is achieved by The reagent used is, for example, t-butyldimethylsilyl chloride, t-butyldimethylsilyl triflate, t-butyldimethylsilylimidazole, Nt-butyldimethylsilyl-N-methyltrifluoroacetamide and the like. −
Butyldimethylsilyl chloride. The base used is, for example, an organic base such as imidazole, triethylamine, 4-dimethylaminopyridine, lutidine, pyridine and the like, preferably triethylamine. The inert solvents used are halogenated hydrocarbons such as dichloromethane and chloroform, ethers such as tetrahydrofuran, amides such as dimethylformamide and dimethylacetamide, preferably halogenated hydrocarbons (dichloromethane). Or amides (dimethylformamide). The reaction temperature is from -10 to 40C, preferably from 0 to 10C. The reaction time is 1 hour to 10 hours, preferably 1 to 2 hours.

The second step is the step of converting the compound (4) into a compound (5) by asymmetric dihydroxylation, in which the compound (4) is reacted with the compound (4) in the presence of a dihydroxylating agent (oxidizing agent) in an inert solvent. This is achieved by The dihydroxylating agent used is, for example, an osmium compound having an asymmetric ligand, preferably a combination of a dihydroquinidine-phthalazine derivative and osmium tetroxide. The inert solvent used is an aromatic hydrocarbon such as toluene, an ether such as tetrahydrofuran, a halogenated hydrocarbon such as dichloromethane or chloroform, or a mixed solvent of alcohol and water, preferably an alcohol. (T-butyl alcohol) and water. The reaction temperature is 0 to 80 ° C, preferably 0 to 1
0 ° C. The reaction time is 1 hour to 10 hours, preferably 3 to 4 hours.

In the third step, compound (5) is tosylated to give compound (6) in an inert solvent in the presence of a base.
This is achieved by reacting compound (5) with a tosylating agent. The tosylating agent used is, for example, 4-toluenesulfonyl chloride, 4-toluenesulfonic anhydride, preferably 4-toluenesulfonyl chloride. The base used is, for example, triethylamine, 4-dimethylaminopyridine, pyridine and the like, preferably triethylamine. The inert solvents used are, for example, halogenated hydrocarbons such as dichloromethane, chloroform, ethers such as tetrahydrofuran, dioxane or pyridine, preferably halogenated hydrocarbons (dichloromethane). Reaction temperature is 0 to 40 ° C
And preferably 20 to 40 ° C. Reaction time is 1
Hours to 10 hours, preferably 3 to 4 hours.

In the fourth step, the compound (6) is reacted with ethanolamine to give a compound (7).
This is achieved by reacting compound (6) with ethanolamine in the presence of a metal salt. Metal salts used are, for example, lithium perchlorate, sodium perchlorate, metal perchlorates such as magnesium perchlorate, zinc chloride,
Zinc salts such as zinc trifluoromethanesulfonate, preferably metal perchlorates (lithium perchlorate)
It is. The inert solvent is, for example, an aromatic hydrocarbon such as toluene, a ketone such as acetone, an ether such as diethyl ether or a nitrile such as acetonitrile, and preferably a nitrile (acetonitrile). . The reaction temperature is 0 to 50 ° C, preferably 20 to 40 ° C. The reaction time is 1 hour to 10 hours, preferably 2 to 3 hours.

The fifth step is a step in which the amino group of compound (7) is protected to give compound (8), which is achieved by reacting compound (7) with an amino group-protecting reagent in an inert solvent. . The protecting reagent used is, for example, di-t-
Examples thereof include butyl dicarbonate and 2- (t-butoxycarbonyloxyimino) -2-phenylacetonitrile, and preferably di-t-butyl dicarbonate. Inert solvents used include, for example, halogenated hydrocarbons such as dichloromethane and chloroform, aromatic hydrocarbons such as toluene, nitriles such as acetonitrile, ethers such as tetrahydrofuran and dioxane, or methanol and ethanol. And preferably halogenated hydrocarbons (dichloromethane). The reaction temperature is 0 to 40 ° C, preferably 20 to 40 ° C. The reaction time is 1 hour to 10 hours, preferably 1 to 2 hours.

The sixth step is a step of cyclizing the compound (8) by a Mitsunobu reaction to give the compound (9), which is achieved by reacting the compound (8) in an inert solvent in the presence of a condensing agent. The condensing agent used is, for example, diethyl azodicarboxylate, diisopropyl azodicarboxylate,
Dicyclohexylazodicarboxylate and the like are used together with triphenylphosphine, tripropylphosphine, tributylphosphine and the like, and preferably, diethylazodicarboxylate and triphenylphosphine are both used. The inert solvent used is, for example, tetrahydrofuran, ethers such as dioxane, aromatic hydrocarbons such as toluene, esters such as ethyl acetate, or halogenated hydrocarbons such as dichloromethane. Is an aromatic hydrocarbon (toluene). The reaction temperature is 0 to 50 ° C, preferably 0 to 10 ° C. The reaction time is 1 hour to 10 hours,
Preferably, it is 1 to 2 hours.

The seventh step is a step of deprotecting compound (9) to give compound (10), which is achieved by reacting compound (9) with an acid in an inert solvent. Acids used are, for example, hydrochloric acid, mineral acids such as sulfuric acid, trifluoroacetic acid,
Organic acids such as 4-toluenesulfonic acid and the like, preferably mineral acids (hydrochloric acid). Inert solvents used are, for example, ethers such as tetrahydrofuran and dioxane, esters such as ethyl acetate or alcohols such as ethanol, preferably ethers (dioxane). The reaction temperature is 20 to 70 ° C,
Preferably it is 50 to 60 ° C. The reaction time is 1 hour to 10 hours, preferably 1 to 2 hours.

In the eighth step, compound (10) and compound (1)
Reacting with compound (1) to give compound (12) in an inert solvent in the presence of a base in the presence of a base,
To achieve. The base used is, for example, an organic base such as triethylamine, 4-dimethylaminopyridine, pyridine or the like, preferably triethylamine. The inert solvent used is, for example, dichloromethane,
Halogenated hydrocarbons such as chloroform, ethers such as tetrahydrofuran and dioxane, or pyridine, preferably halogenated hydrocarbons (dichloromethane). The reaction temperature is 0 to 40 ° C, preferably 0 to 10 ° C. The reaction time is 1 hour to 10 hours, preferably 2 to 3 hours.

The ninth step is the step of converting the compound (12) into a compound (13) by reacting the compound (12) with a mesylating agent in the presence of a base in an inert solvent. The mesylating agent used is, for example, methanesulfonyl chloride, methanesulfonic anhydride and the like, preferably methanesulfonyl chloride. The base used is, for example, an organic base such as triethylamine, 4-dimethylaminopyridine or pyridine, preferably triethylamine. The inert solvents used are, for example, halogenated hydrocarbons such as dichloromethane, chloroform, ethers such as tetrahydrofuran, dioxane or pyridine, preferably halogenated hydrocarbons (dichloromethane). The reaction temperature is 0 to 40 ° C, preferably 0 to 5 ° C. The reaction time is 1 hour to 10 hours, preferably 2 to 3 hours.

The tenth step is a step of producing compound A,
It is achieved by reacting compound (13) with compound (14) in an inert solvent in the presence of iodide and a base, and converting the compound to hydrochloric acid. The base used is, for example, an alkali metal carbonate such as potassium carbonate, an alkali metal bicarbonate such as sodium bicarbonate or an organic base such as triethylamine, preferably an alkali metal bicarbonate (sodium bicarbonate). ). The iodide used is, for example, an alkali metal iodide such as lithium iodide, sodium iodide or potassium iodide, preferably potassium iodide. Both a base and an alkali metal iodide are used, preferably an alkali metal bicarbonate and an alkali metal iodide (sodium hydrogen carbonate and potassium iodide). The inert solvent used is, for example, amides such as dimethylformamide and dimethylacetamide, ethers such as tetrahydrofuran and dioxane, and preferably amides (dimethylacetamide). The reaction temperature is 50 to 100 ° C, preferably 70 to 80 ° C. The reaction time is 1 hour to 20 hours, preferably 8 to 10 hours.
Hydrochlorination is achieved by stirring the purified and isolated compound with a 4N hydrochloric acid-dioxane solution at room temperature and distilling off the solvent. The reaction temperature is 0 to 30 ° C, preferably 10 to 20 ° C. The reaction time is 10 minutes to 1 hour, preferably 10 to 30 minutes.

After completion of each reaction, each target compound is collected from the reaction mixture according to a conventional method. For example, after completion of the reaction, the solvent is distilled off from the reaction solution or the reaction mixture is appropriately neutralized, and if there is any insoluble matter, the insoluble matter is removed by filtration. Extract with such a water-immiscible organic solvent, wash the extract with saturated saline, etc.
After drying over anhydrous magnesium sulfate or the like, it can be obtained by distilling off the solvent. If necessary, the obtained target compound can be further purified by a conventional method, for example, distillation, chromatography and the like. Hereinafter, the present invention will be described with reference to Examples, but the present invention is not limited thereto.

[0043]

EXAMPLES Example 1 3- (3,4-dichlorophenyl) -3-butene-1-
1.0 g of all molecular sieve 4A
The mixture was suspended and stirred, and 0.8 ml of a trifluoroborane-ethyl ether complex was added. After stirring at room temperature for 1.0 hour, the mixture was cooled to -10 ° C, and paraformaldehyde 180 was added.
mg, 1.0 g of 3,4-dichloro-α-methylstyrene
10 ml of a dichloromethane solution of
Stirred for hours. After adding 20 ml of a saturated aqueous solution of sodium hydrogencarbonate to the reaction solution and removing the molecular sieve by filtration, the organic layer was separated. The organic layer was washed with saturated saline 20m
After washing once with water and once with 20 ml of water and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 1.15 g (yield: 99.1%) of the target compound as an oil. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDC
l ₃ ) δ ppm: 2.75 (2H, t, J = 6.3)
Hz), 3.71 (2H, t, J = 6.3 Hz), 5.
18 (1H, s), 5.39 (1H, s), 7.02-
7.51 (3H, m).

Example 2 3- (4-Fluorophenyl) -3-buten-1-ol 1.0 g of molecular sieve 4A was added to dichloromethane 10
The mixture was suspended and stirred, and 0.9 ml of a trifluoroborane / ethyl ether complex was added. After stirring at room temperature for 1.0 hour, the mixture was cooled to -10 ° C and paraformaldehyde 245 was added.
mg and 4-fluoro-α-methylstyrene (1.0 g) in dichloromethane (10 ml) were sequentially added, and the mixture was stirred at the same temperature for 2 hours. Saturated aqueous sodium hydrogen carbonate solution 20
After the addition of ml, the molecular sieve was removed by filtration, and the organic layer was separated. The organic layer was washed once with 20 ml of saturated saline and once with 20 ml of water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure to obtain 1.20 g of the desired compound as an oil (yield 98.4%). ) Got. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDC
l ₃ ) δ ppm: 2.39 (2H, t, J = 6.6)
Hz), 3.35 (2H, t, J = 6.6 Hz), 4.
77 (1H, s), 4.99 (1H, s), 6.62
(2H, m), 7.01-7.43 (2H, m).

Example 3 3- (3,4-difluorophenyl) -3-butene-1
-1.0 g of all molecular sieve 4A in dichloromethane 10
Then, 1.0 ml of a trifluoroborane / ethyl ether complex was added. After stirring at room temperature for 1.0 hour, the mixture was cooled to -10 ° C and paraformaldehyde 217 was added.
mg, 3,4-difluoro-α-methylstyrene 1.0
g of dichloromethane solution were sequentially added, and the mixture was stirred at the same temperature for 2 hours. After adding 20 ml of a saturated aqueous solution of sodium hydrogencarbonate to the reaction solution and removing the molecular sieve by filtration, the organic layer was separated. The organic layer was washed with saturated saline 20
After washing once with water and once with 20 ml of water and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 1.10 g (yield: 91.7%) of the target compound as an oil. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDC
l ₃ ) δ ppm: 2.29 (2H, t, J = 6.6)
Hz), 3.29 (2H, t, J = 6.6 Hz), 4.
74 (1H, s), 4.93 (1H, s), 6.50-
6.83 (2H, m).

Example 4 3-Phenyl-3-buten-1-ol 1.0 g of molecular sieve 4A was added to dichloromethane 10
Then, 1.04 ml of a trifluoroborane / ethyl ether complex was added thereto. After stirring at room temperature for 1.0 hour, the mixture was cooled to −10 ° C., and paraformaldehyde 28
3 mg and 10 ml of a dichloromethane solution of 1.0 g of α-methylstyrene were sequentially added, followed by stirring at the same temperature for 2 hours. 20 ml of a saturated aqueous sodium hydrogen carbonate solution was added to the reaction solution,
After removing the molecular sieve by filtration, the organic layer was separated. The organic layer was washed once with 20 ml of saturated saline,
After washing once with water and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure.
0 g (79.4% yield) was obtained. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDC
l ₃ ) δ ppm: 2.73 (2H, t, J = 6.5)
Hz), 3.66 (2H, t, J = 6.5 Hz), 5.
10 (1H, s), 5.35 (1H, s), 7.15-
7.36 (5H, m).

Example 5 3-Phenyl-3-buten-1-ol 0.5 g of molecular sieve Y was added to 10 m of dichloromethane.
The suspension was stirred and stirred, and 1.04 ml of a trifluoroborane-ethyl ether complex was added. After stirring at room temperature for 1.0 hour, the mixture was cooled to −10 ° C., and paraformaldehyde 283 was added.
mg and 1.0 g of α-methylstyrene in 10 ml of a dichloromethane solution were sequentially added, and the mixture was stirred at the same temperature for 2 hours. After adding 20 ml of a saturated aqueous solution of sodium hydrogencarbonate to the reaction solution and removing the molecular sieve by filtration, the organic layer was separated. The organic layer was washed once with 20 ml of saturated saline solution and 20 m of water.
After washing once with l and drying over anhydrous magnesium sulfate,
The solvent was distilled off under reduced pressure to give the target compound as an oily substance in 1.21
g (96.8% yield). The physical properties of the obtained target compound were the same as those obtained in Example 4.

Reference Example 1 Potassium 3,4-dichloro-α-methylstyrene t-butoxide 44.6 g of toluene 750 m
To the suspension was added 141.8 g of methyltriphenylphosphonium bromide, and the mixture was stirred at room temperature for 4.0 hours. Further, 150 ml of a toluene solution of 50.0 g of 3,4-dichloroacetophenone was added, and the mixture was stirred at the same temperature for 1 hour.
500 ml of a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, and the organic layer was separated. The organic layer was washed with saturated saline 500 ml
After washing once with 500 ml of water and drying over anhydrous magnesium sulfate, toluene was distilled off under reduced pressure. The residue was purified by distillation (bp: 80-82 ° C / 3 mmHg) to give 45.7 g of the desired compound as a colorless oil (yield: 92.3).
%)Obtained. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDC
l ₃ ) δ ppm: 2.03 (3H, s), 5.08
(1H, s), 5.31 (1H, s), 6.94-7.
67 (3H, m).

Reference Example 2 Methyltriphenylphosphonium bromide was added to a suspension of 8.1 g of 4-fluoro-α-methylstyrene potassium t-butoxide in 75 ml of toluene.
5.9 g was added, and the mixture was stirred at room temperature for 4.0 hours. 4 more
-Toluene solution 15 of 5.0 g of fluoroacetophenone
Then, the mixture was stirred at the same temperature for 1 hour. 50 ml of a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, and the organic layer was separated. The organic layer was washed once with 50 ml of a saturated saline solution and 50 ml of water.
And dried over anhydrous magnesium sulfate, and toluene was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane) to give 3.2 g (yield: 65.1%) of the target compound as a colorless oil. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDC
l ₃ ) δ ppm: 2.12 (3H, s), 5.37
(1H, s), 5.35 (1H, s), 6.96-7.
05 (2H, m), 7.33-7.59 (2H, m).

Reference Example 3 Methyltriphenylphosphonium bromide was added to a suspension of 7.2 g of 3,4-difluoro-α-methylstyrene potassium t-butoxide in 75 ml of toluene.
2.9 g was added, and the mixture was stirred at room temperature for 4.0 hours. Further, 15 ml of a toluene solution of 5.0 g of 3,4-difluoroacetophenone was added, and the mixture was stirred at the same temperature for 1 hour. 50 ml of a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, and the organic layer was separated. The organic layer was washed once with 50 ml of saturated saline and once with 50 ml of water, dried over anhydrous magnesium sulfate, and then toluene was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane) to give the target compound as a colorless oil (3.7 g, yield 73.9%).
Obtained. ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDC
l ₃ ) δ ppm: 2.10 (3H, s), 5.04
(1H, s), 5.34 (1H, s), 6.86-7.
43 (3H, m).

[0051]

According to the production method of the present invention, a 3-buten-1-ol compound useful as an intermediate in the development of functional substances such as pharmaceuticals, agricultural chemicals, liquid crystals, and materials can be obtained with higher selectivity and yield than conventional methods. Therefore, it is useful as an industrial production method.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07C 205/14 C07C 205/14 255/15 255/15 C07F 5/02 C07F 5/02 A // C07B 61 / 00 300 C07B 61/00 300 (72) Inventor Takebayashi ▲ Toyo Riku 173 Nakahara Kamishuku, Hiratsuka-shi, Kanagawa Sankyo Stock Company In-house F-term (reference) 4H006 AA02 AC41 BA31 BA69 BA71 BB11 BB16 BC10 BC19 BE56 BN10 DA15 4H039 CA60 CF40 4H048 AA03 AB40 AC21 BA09 BA31 BA33 BA45 BA47 BA71 BE56 VA11 VA20 VA22 VA75 VB10

Claims (12)

[Claims] 1. A compound of the general formula [Wherein, R ¹ represents a linear or branched alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, or a carbon number which may have a substituent. An aryl group having 6 to 10 carbon atoms (the substituent may be a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms) An alkyl group having 1 to 6 carbon atoms, a linear or branched halogenated alkyl group having 1 to 6 carbon atoms,
Linear or branched aliphatic acyl group having
A linear or branched aliphatic acyloxy group having 1 to 6 carbon atoms, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group or a cyano group; Represents a group. ). And a compound represented by the general formula: (Wherein R ² represents a hydrogen atom, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms) A linear or branched halogenated alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 6 carbon atoms) is a trifluoroborane compound And reacting in the presence of an aluminosilicate. (Wherein, R ¹ and R ² have the same meanings as described above.)
A method for producing a 3-buten-1-ol derivative represented by the formula: 2. The method according to claim 1, wherein R ¹ has 3 to 5 carbon atoms.
A branched alkyl group having 5 to 6 carbon atoms, a cycloalkyl group having 5 to 6 carbon atoms, and an aryl group having 6 to 10 carbon atoms which may have a substituent (the substituent has 1 to 5 carbon atoms). Straight or branched alkyl halide group having 1 to 6 carbon atoms, straight or branched aliphatic acyl group having 1 to 6 carbon atoms, and straight or branched aliphatic acyl group having 1 to 6 carbon atoms. A linear or branched aliphatic acyloxy group, a linear or branched alkoxycarbonyl group having 1 to 6 carbon atoms, a halogen atom, a nitro group or a cyano group), and R ² is a hydrogen atom, an alkoxycarbonyl group having 1 to 3 carbon atoms, 1 to 3 carbon atoms
Wherein the alkyl group has 1 to 3 carbon atoms, the alkyl group having 1 to 3 carbon atoms is substituted with 1 to 3 fluorine or chlorine atoms, or the cycloalkyl group has 5 to 6 carbon atoms. 3. The method according to claim 1, wherein R ¹ is an aryl group having 6 to 10 carbon atoms which may have a substituent (the substituent may be a linear or branched aryl group having 1 to 3 carbon atoms). A group in which 1 to 3 fluorine or chlorine atoms are substituted on a branched alkyl group, an aliphatic acyl group having 1 to 3 carbon atoms, an aliphatic acyloxy group having 1 to 3 carbon atoms,
A straight-chain or branched alkoxycarbonyl group having 1 to 3 carbon atoms, a halogen atom, a nitro group or a cyano group. Wherein R ² is a hydrogen atom, methoxycarbonyl, ethoxycarbonyl, methyl, ethyl, propyl or trichloromethyl group. 4. The method according to claim 1, wherein R ¹ is a phenyl group which may have a substituent (the substituent is selected from the group consisting of a trifluoromethyl group, an acetyl group, a halogen atom, a nitro group and a cyano group). Wherein R ² is a hydrogen atom. 5. The method according to claim 1, wherein R ¹ is a phenyl group optionally having one or two substituents selected from the group consisting of fluorine and chlorine atoms, and R ² is a hydrogen atom. Method. 6. The trifluoroborane compound according to claim 1, wherein the trifluoroborane compound is trifluoroborane, a trifluoroborane / alkyl ether complex having 1 to 4 carbon atoms, or a trifluoroborane / alkyl sulfide having 1 to 4 carbon atoms. A production method which is a complex or a trifluoroborane / tetrahydrofuran complex. 7. The method according to claim 1, wherein the trifluoroborane compound is a trifluoroborane / alkyl ether complex having 1 to 4 carbon atoms. 8. The method according to claim 1, wherein the trifluoroborane compound is a trifluoroborane-ethyl ether complex. 9. The method according to claim 1, wherein the aluminosilicate is natural zeolite, synthetic zeolite or montmorillonite. 10. The method according to claim 1, wherein the aluminosilicate is a synthetic zeolite. 11. The method according to claim 1, wherein the aluminosilicate is a 3A molecular sieve, 4A molecular sieve, 5A molecular sieve, X molecular sieve or Y molecular sieve. 12. The method according to claim 1, wherein the aluminosilicate is a 4A molecular sieve, an X molecular sieve or a Y molecular sieve.