JP2752260B2 - Phenylcarbamate derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION

Embedded image (In the formula 1, X is .R ¹ represents a halogen atom represents a hydrogen atom, a cycloalkyl group having a carbon number of 3-8, an alkynyl group, or R ³ OCO group having a carbon number of 2 to 5, R ² and R ³
Represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group. R above
Represented by ¹ Resid black alkyl group, A Rukiniru group, a halogen atom, a cyano group, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, alkoxycarbonyl group having 1 to 6 carbon atoms It may be substituted. The present invention relates to a phenyl carbamate derivative represented by the formula and an intermediate thereof.

Further, the present invention relates to Japanese Patent Application Laid-Open No. Sho 62-17406.
Compound useful as an active ingredient of the herbicide described in No. 5 (Formula 9)

Embedded image (In the formula 9, X represents a halogen atom. R ⁴ has 1 carbon atom.
12 alkyl group, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group or an alkynyl group having 2 to 5 carbon atoms having 2 to 5 carbon atoms, the alkyl group represented by R ^4, a cycloalkyl group, an alkenyl The group or alkynyl group may be substituted with a halogen atom, a cyano group, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or an alkoxycarbonyl group having 1 to 6 carbon atoms. ) Is to provide a method for producing production intermediate of oxazolidinedione derivative represented by the.

[0003]

2. Description of the Related Art Many carbamate derivatives have been known so far, but the carbamate derivative represented by the formula 1 is a novel compound.

[0004]

The conventionally known method for producing an oxazolidinedione derivative represented by the formula 9 is not always satisfactory in the purity and yield of the product.

[0005]

Means for Solving the Problems The present inventors have found that the oxazolidinedione derivative represented by the formula 9 which is a compound useful as a herbicide described in JP-A-62-174065 is industrially advantageous. As a result of intensive studies on excellent and excellent production methods, they have found that the phenylcarbamate derivative represented by the formula 1 can be an important production intermediate. For example, the oxazolidinedione derivative represented by the formula 9 can be obtained by the reaction shown in the following Reference Example. The present invention has been completed by finding that it can be obtained in a yield.

Next, the method for producing the phenyl carbamate derivative which is the compound of the present invention will be described in detail.

Each of the phenyl carbamate derivatives belonging to the phenyl carbamate derivative represented by the formula 1, Formulas 4, 5 and 7 can be produced according to the route shown in the following reaction formula.

Embedded image (Wherein, X, R ² and R ³ represent the same meaning as described above.
⁴ represents an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 5 carbon atoms or an alkynyl group having 2 to 5 carbon atoms, and an alkyl group represented by R ⁴ above; A cycloalkyl group, an alkenyl group, and an alkynyl group are a halogen atom, a cyano group, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms,
6 may be substituted with an alkoxycarbonyl group.
Y represents a leaving group. )

That is, in the step 1, a phenyl carbamate derivative represented by the formula 4 of the compound of the present invention is produced by reacting an aniline derivative represented by the formula 2 with a chloroformate represented by the formula 3 in the presence of a base. This is the step of performing

Usually, the reaction is carried out in an organic solvent at a temperature from room temperature to the boiling point of the solvent used, preferably at a temperature of 40 to 100 ° C., and the reaction is usually completed in 0.5 to 12 hours.

As the organic solvent used, benzene,
Aromatic hydrocarbons such as toluene and xylene; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; ethers such as diethyl ether, tetrahydrofuran, dioxane and dimethoxyethane; nitriles such as acetonitrile; dimethylformamide and dimethyl sulfoxide; In general, polar solvents such as ketones, nitriles, and dimethylformamide are used.

Examples of the base to be used include alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal bicarbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, alkali metal hydrides such as sodium hydride, and sodium methoxy. , Sodium ethoxide, potassium-
alkali metal alkoxides such as t-butoxide, triethylamine, pyridine, dimethylaminopyridine, N-
An organic base such as methylmorpholine can be used.

[0012] Usually, the reaction is carried out in such a manner that chloroformate (formula 3) is used in an amount of from 1.0 to 1 equivalent of the aniline derivative (formula 2).
2.0 equivalents, preferably 1.0 to 1.2 equivalents are used, and the base is 1.0 to 5.0 equivalents, preferably 1.
By using 5 to 3.0 equivalents, the desired product can be obtained in good yield.

After the completion of the reaction, the reaction mixture is added to water or a weakly acidic aqueous solution, and the precipitated crystals are isolated by filtration or extracted with an organic solvent, followed by ordinary treatment such as drying and concentration. By doing so, the desired phenyl carbamate derivative (Formula 4) can be obtained.

Step-2 is represented by Chemical Formula 5 of the present invention by selectively hydrolyzing only the carbonate ester portion of the phenylcarbamate derivative represented by Formula 4 obtained in Step-1 in the presence of a base. This is a step of producing a phenyl carbamate derivative.

Usually, the reaction is carried out in a solvent at a temperature from room temperature to the boiling point of the solvent used, preferably at a temperature from room temperature to 80 ° C., and the reaction is usually completed in 0.5 to 12 hours.

Examples of the solvent used include water, alcohols such as methanol, ethanol and isopropyl alcohol; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone; ethers such as diethyl ether, tetrahydrofuran and dioxane; and nitriles such as acetonitrile. , A solvent such as dimethylformamide, dimethylsulfoxide and the like, and a mixed solvent thereof can be used, but water or a protic solvent such as alcohols such as methanol, ethanol and isopropyl alcohol or a solvent such as these and other organic solvents. Is preferred because the reaction is quick and the yield is good.

Examples of the base used include carbonates of alkali metals such as sodium carbonate and potassium carbonate, bicarbonates of alkali metals such as sodium hydrogen carbonate and potassium hydrogen carbonate, and alkali metal alkoxides such as sodium methoxide and sodium ethoxide. And alkali metal salts such as alkali metal hydroxides such as sodium hydroxide and potassium hydroxide. The amount of the base is usually 0.1 to 5.0 equivalents, preferably 0.2 to 2.0 equivalents, in terms of metal, relative to 1 equivalent of the phenyl carbamate derivative (formula 5).

After completion of the reaction, the reaction mixture is added to water or a weakly acidic aqueous solution, and the precipitated crystals are isolated by filtration, or extracted with an organic solvent, and subjected to ordinary processing operations such as drying and concentration. By doing so, the desired phenyl carbamate derivative (formula 5) can be obtained.

In the step-3, the phenylcarbamate derivative represented by the formula 5 obtained in the step-2 is reacted with the compound represented by the formula 6 in the presence of a base, and the phenylcarbamate represented by the formula 7 of the present invention is reacted. This is a step of producing a derivative.

The reaction is usually carried out in an organic solvent at a temperature from room temperature to the boiling point of the solvent used, preferably at a temperature from room temperature to 100 ° C., and the reaction is usually completed in 0.5 to 12 hours.

Examples of the solvent used include aromatic hydrocarbons such as benzene, toluene and xylene; ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone;
Diethyl ether, tetrahydrofuran, dioxane,
Ethers such as dimethoxyethane, methanol, ethanol, alcohols such as isopropyl alcohol, nitriles such as acetonitrile, dimethylformamide, dimethyl sulfoxide and the like or a mixed solvent thereof can be exemplified, usually, ketones, alcohols, nitriles, Solvents such as dimethylformamide are preferred in terms of good yield.

Examples of the base used include carbonates of alkali metals such as sodium carbonate and potassium carbonate, bicarbonates of alkali metals such as sodium hydrogen carbonate and potassium hydrogen carbonate, alkali metal hydrides such as sodium hydride, and sodium methoxy. , Sodium ethoxide, potassium-
Alkali metal alkoxides such as t-butoxide and alkali metal hydroxides such as sodium hydroxide and potassium hydroxide can be used.

In general, the reaction is carried out in an amount of 1.0 to 2.0 equivalents based on 1 equivalent of the phenyl carbamate derivative (formula 5).
Preferably, 1.1 to 1.2 equivalents are used, and the base is used in an amount of 1.0 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, in terms of metal.

After completion of the reaction, the reaction mixture is added to water or a weakly acidic aqueous solution, and the precipitated crystals are isolated by filtration, or extracted with an organic solvent, and subjected to ordinary processing operations such as drying and concentration. By doing so, the desired phenyl carbamate derivative (Formula 7) can be obtained.

The reaction of the step-3 can be carried out in the presence of a catalyst, such as sodium bromide, potassium bromide,
Examples thereof include alkali metal salts such as sodium iodide and potassium iodide, and quaternary ammonium salts such as benzyltriethylammonium chloride and tetrabutylammonium chloride, and mixtures thereof. Usually, a phenylcarbamate derivative (formula 5) ) Is used in an amount of 0.001 to 0.5 equivalent.

By carrying out Step 2 and Step 3 sequentially or simultaneously in the same reaction vessel, the phenyl carbamate derivative (Formula 7) can be obtained without isolating the phenyl carbamate derivative (Formula 5). It can also be produced directly from (Equation 4).

That is, the alkali metal salt is added to the phenyl carbamate derivative (formula 4) in an amount of from 1.0 to 1.0 in terms of metal.
The reaction is carried out using 5.0 equivalents, and the resulting alkali metal phenoxide of the phenyl carbamate derivative (formula 5) is reacted with the formula 6 sequentially or simultaneously, whereby a phenyl carbamate derivative (formula 7) can be obtained.

The reaction is preferably carried out in the solvent shown in Step-2, at a temperature from room temperature to the boiling point of the solvent used, preferably at a temperature from room temperature to 80 ° C.

Chloroformate as a raw material (formula 3)
Can be used as it is, but it can be easily produced from phosgene or an equivalent thereof and alcohols.

As alcohols, methanol, ethanol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol, 2-ethylhexyl alcohol, allyl alcohol, crotyl alcohol, methallyl alcohol, prenyl alcohol, phenol, benzyl alcohol and the like are used. Can be

Examples of the chloroformate represented by the formula 3, including those commercially available, include methyl chloroformate, ethyl chloroformate, propyl chloroformate, isopropyl chloroformate, butyl chloroformate, isobutyl chloroformate, t-butyl chloroformate, and chloroformate. Pentyl acid, hexyl chloroformate, 2-ethylhexyl chloroformate, allyl chloroformate, crotyl chloroformate, phenyl chloroformate, benzyl chloroformate and the like can be exemplified.

As the compound represented by the formula 6, commercially available halides can be used as they are,
An alcohol can be reacted with a sulfonic acid chloride such as benzenesulfonyl chloride, p-toluenesulfonyl chloride, methanesulfonyl chloride, and trifluoromethanesulfonyl chloride in the presence of a base to obtain a sulfonate, which can be used for the reaction.

Accordingly, the compounds represented by the formula 6, including commercially available compounds, include methyl iodide, methyl bromide, ethyl iodide, ethyl bromide, isopropyl iodide,
Isopropyl bromide, butyl iodide, isobutyl iodide,
-Sec-butyl iodide, pentyl iodide, hexyl iodide, cyclopropyl bromide, cyclopentyl bromide, cyclohexyl bromide, allyl chloride, allyl bromide, crotyl chloride, methallyl chloride, 2,
3-dichloro-1-propene, 4-bromo-1-butene, 1-bromo-3-methyl-3-butene, cyanomethylbromide, 1-cyanoethylbromide, difluorochloromethane, difluorobromomethane, 1-bromo-3
-Fluoropropane, propargyl bromide, 3-bromo-1-butyne, 1-bromo-3-pentyne, methyl chloroacetate, ethyl chloroacetate, methyl bromoacetate, 2-
Methyl chloropropionate, methyl 2-bromopropionate, ethyl 2-bromopropionate, methyl 2-bromobutanoate, cyclopentylbenzenesulfonate, cyclopentyl p-toluenesulfonate, cyclopentylmethanesulfonate, cyclohexyl p-toluenesulfonate, propargyl p-toluenesulfonate,
Propargyl trifluoromethanesulfonate, 3-
(1-butynyl) p-toluenesulfonate, 3- (1
-Butynyl) trifluoromethanesulfonate, 3-
(1-butynyl) methanesulfonate and the like can be exemplified.

Further, the aniline derivative represented by the formula 2 has a novel compound depending on the substituent, and can be produced, for example, according to the route shown in the following reaction formula.

Embedded image (In the formula, X and R ³ represent the same meaning as described above.)

That is, the literature [GCFinger, J. Am. Chem. S
oc., 81, 94 (1959)] 2-halogeno-4 which is a known compound
-Fluorophenol (Formula 10) can be reacted with a chloroformate represented by Formula 13 in the presence of a base such as sodium hydroxide or potassium hydroxide to obtain a phenyl carbonate derivative (Formula 11).

Examples of the chloroformate represented by the formula 13 include methyl chloroformate, ethyl chloroformate, propyl chloroformate, isopropyl chloroformate, butyl chloroformate, isobutyl chloroformate, t-butyl chloroformate,
Examples include pentyl chloroformate, hexyl chloroformate, 2-ethylhexyl chloroformate, allyl chloroformate, crotyl chloroformate, phenyl chloroformate, benzyl chloroformate, and the like.

Next, a nitro group is introduced by a method such as a method of nitrating a benzene ring, for example, a method using a mixed acid of nitric acid and sulfuric acid, a method using fuming nitric acid, and the like.
To a nitrobenzene derivative represented by

Further, this is a method usually used for reduction of an aromatic nitro compound, for example, a method using reduced iron / acetic acid, reduced iron / hydrochloric acid, zinc / hydrochloric acid, sodium sulfide, palladium carbon, palladium black, An aniline derivative represented by Formula 2 which is a raw material for producing the compound of the present invention by converting a nitro group into an amino group by a catalytic reduction method using palladium asbestos, platinum carbon, platinum oxide (Adams catalyst) or the like as a catalyst. Can be obtained.

In the compounds represented by the formulas 11, 12 and 2, when R ³ is a short-chain alkyl group such as a methyl group, the properties of these compounds are solid whereas Those having a longer-chain alkyl group such as an isobutyl group are liquids, and are extremely difficult to handle in operations such as packing into a reactor, isolation, drying and the like in industrial production. This is advantageous in that it is simple.

The thus obtained phenyl carbamate derivative of the present invention (formula 7) can be led to an oxazolidine derivative having herbicidal activity represented by formula 9 by the route shown in the following reaction formula. (See the reference example below)

[0041]

Embedded image (Wherein, X, R ² and R ⁴ represent the same meaning as described above.)

In the step-1, an N- (substituted phenyl) carbamic acid ester (formula 7) is hydrolyzed to give an aniline derivative (formula 14) wherein X and R ⁴ have the same meanings as described above. ] Is obtained.

The reaction is carried out in the presence of a base. As the base, an aqueous solution of a metal hydroxide such as sodium hydroxide, potassium hydroxide or calcium hydroxide can be used, and an alcohol such as methanol, ethanol or isopropyl alcohol can be used. It is preferable to carry out the reaction in a mixed solvent with a system solvent because the yield is good.

In the step-2, the amino group of the aniline derivative (formula 14) is converted into an isocyanato group using phosgene or a phosgene equivalent, and the phenylisocyanate derivative (formula 15) wherein X and R ⁴ are Has the same meaning as ] Is obtained.

The reaction can be carried out in an organic solvent, and a solvent such as ethyl acetate, benzene, or toluene can be used. The reaction may be carried out by introducing a solution of the aniline derivative (Formula 14) into a solution of phosgene or its equivalent, or by adding phosgene or its equivalent to a solution of the aniline derivative (Formula 14). The reaction is performed at a low temperature of room temperature or lower while the reaction substrate is added, and then heated to about 100 ° C. to terminate the reaction. After the completion of the reaction, the isocyanate derivative (Formula 15) can be obtained in good yield by distilling off the solvent.

In the step-3, the isocyanate derivative (formula 15) obtained in the step-2 and 2-hydroxy-3
-Methyl-3-butenoate (formula 16) in the presence of a base to give a herbicide active ingredient 3
N- (2-fluoro-4-halogeno-5-alkoxyphenyl) -5-isopropylidene-1,3-oxazolidine-2,4-dione (Formula 9) wherein X and R ⁴ have the same meanings as described above. Represents ] Can be converted to

The reaction is carried out in an organic solvent in triethylamine, tributylamine, N-methylmorpholine, pyridine,
The reaction is carried out in the presence of a base such as amines such as N, N-dimethylaniline and alkali metal carbonates such as carlim carbonate and sodium carbonate. The amount of the base is not particularly limited, and a catalytic amount is sufficient. As the organic solvent, toluene, benzene, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, N, N-dimethylformamide and the like can be used. Although the reaction proceeds even at room temperature depending on the type of the solvent, the reaction time can be shortened by performing the reaction at room temperature to reflux of the solvent.

Hereinafter, the present invention will be described in more detail with reference to Examples and Reference Examples, but the present invention is not limited to these reaction examples.

[0049]

EXAMPLES Example 1

Embedded image

2-fluoro-4-chloro-5-isobutyloxycarbonyloxyaniline (4.20 g, 1
6.1 mmol) and potassium carbonate (2.22 g, 1
To a solution of 6.1 mmol) in acetone (100 ml) was added methyl chloroformate (2.27 g, 24.0 mmol), and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction mixture is
Hydrochloric acid (100 ml) was added, and the precipitated solid was isolated by filtration. This was recrystallized from ether / hexane to give pure N- (2-fluoro-4-chloro-5-isobutyloxycarbonyloxyphenyl).
White solid of methyl carbamate (4.91 g, yield 9)
5.7%).

Melting point: 72.2-78.8 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.00 (6H, d, J = 6.5 Hz), 2.0
5 (1H, t & sep, J = 6.5,6.5Hz), 3.78 (3H, s), 4.03 (2H, d, J = 6.5
Hz), 6.85 (1H, brs), 7.08 (1H, d, J _HF = 10.2Hz), 8.10 (1H, d, J
_HF = 7.5Hz) ppm.IR (KBr disk): 1773,1733,1545,1285,1235,1180cm ^-1 .

Embodiment 2

Embedded image

2-fluoro-4-chloro-5-methoxycarbonyloxyaniline (22.0 g, 100 mmol
l) and potassium carbonate (13.8 g, 100 mmol)
Ethyl chloroformate (1 ml) in acetone (300 ml) solution
(6.3 g, 150 mmol), and the mixture was heated with stirring at 60 ° C. for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, 1N hydrochloric acid (100 ml) was added, and ethyl acetate (100 ml × 3) was added.
Times). The organic layer was washed with water and dried, and the solvent was distilled off under reduced pressure to obtain a white solid. This was recrystallized from chloroform-hexane to give pure ethyl N- (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate as white crystals (23.3 g, yield 80.2). %).

Melting point: 143.8-147.2 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.13 (3H, t, J = 6.5 Hz), 3.9
2 (3H, s), 4.23 (2H, q, J = 6.5Hz), 6.80 (1H, brs), 7.15 (1H, d,
IR (KBr disk): 1770,1730,1545,1290,1235,1215cm ^-1 .J _HF = 10.5Hz), 8.12 (1H, d, J _HF = 8.0Hz) ppm.

Example 3

Embedded image

2-fluoro-4-chloro-5-methoxycarbonyloxyaniline (2.00 g, 6.86 mm
ol), potassium carbonate (1.42 g, 10.3 mmol)
l) and benzyl chloroformate (1.17 g, 6.86 m)
mol), acetone (20 ml) was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction mixture was diluted with 1N hydrochloric acid (50 m
l) and extracted with ethyl acetate (50 ml x 3). The organic layer was dried and concentrated under reduced pressure to obtain a substantially pure solid of benzyl N- (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate (2.21 g, yield 91.1%). I got

Melting point: 70-72 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 3.62 (3H, s), 3.96 (2H, s),
6.59 (1H, d, J _HF = 5Hz), 7.01 (1H, d, J _HF = 10.0Hz), 7.20 (1H, b
rs), 7.10-7.50 (5H, m) ppm.

Embodiment-4

Embedded image

Ethyl N- (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate (45.2 g, 155 mmol) and potassium carbonate (2
(1.4 g, 155 mmol), ethyl alcohol (200 ml) and water (100 ml) were added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure, 1N hydrochloric acid (300 ml) was added to make the solution acidic, and the mixture was extracted with ethyl acetate (100 ml × 3 times).
The organic layer was dried, concentrated under reduced pressure, and the obtained solid was recrystallized from chloroform / hexane to give pure N-
White crystals of ethyl (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (35.2 g, yield 97.2%) were obtained.

Melting point: 151.5-154.2 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.32 (3H, t, J = 7.2 Hz), 4.2
3 (2H, q, J = 7.2Hz), 5.84 (1H, s), 6.80 (1H, brs), 7.04 (1H, d,
J _HF = 10.5Hz), 7.85 (1H, d, J _HF = 7.5Hz) ppm.IR (KBr disk):
3440,1710,1560,1430,1250cm ^-1 .

Example-5

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Methyl N- (2-fluoro-4-chloro-5-isobutyloxycarbonyloxyphenyl) carbamate (14.0 g, 43.8 mmol) was dissolved in methanol (100 ml), and then potassium carbonate (7.26 g). , 52.5 mmol) at 50 ° C.
The mixture was heated and stirred for hours. After completion of the reaction, the solvent was distilled off under reduced pressure.
The obtained solid is dissolved in acetic acid (20 ml), poured into ice water, and the precipitated solid is filtered and dried to give pure N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamic acid. Methyl white solid (9.60 g,
Yield 99.8%).

Melting point: 140.0 to 141.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.57 (3H, s), 3.78 (3H, s),
5.53 (1H, s), 6.75 (1H, br, s), 7.05 (1H, d, J = 10.5Hz), 7.82
(1H, d, J _HF = 7.5Hz) ppm.IR (KBr disk): 3440,1717,1630,1560,1430,1250cm ^-1 .

Example-6

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A mixture of methyl N- (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate (21.5 g, 77.5 mmol) and potassium carbonate (10.7 g, 77.4 mmol) was added to ethanol ( 50 ml) and water (50 ml).
Allowed to react for hours. After completion of the reaction, the reaction mixture was diluted with 1N hydrochloric acid (1
50 ml) and extracted with ethyl acetate (100 ml × 3 times). The organic layer was dried, concentrated under reduced pressure, and the obtained solid was recrystallized from ether / hexane to give pure methyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate. White solid (15.6 g,
Yield 91.9%). The spectrum data and the like are as shown in Example-5.

Example -7

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Ethyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (1.00 g,
4.28 mmol), potassium carbonate (0.59 g, 4.28 mmol).
Ethyl alcohol (20 ml) was added to 28 mmol), and the mixture was heated under reflux for 2 hours. Then, cyclopentyl paratoluenesulfonate (1.20 g, 5.14 mmol) was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction mixture is
Hydrochloric acid (50 ml) and ethyl acetate (50 ml × 3
Times). The organic layer was dried and concentrated under reduced pressure, and the obtained solid was washed with hexane to obtain almost pure N
Light brown solid of ethyl- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) carbamate (1.
(30 g, yield １００100%).

Melting point: 92.8-97.8 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.33 (3H, t, J = 7.0 Hz), 1.4
0-2.10 (8H, m), 4.32 (2H, q, J = 7.0Hz), 4.88 (1H, m), 6.87 (1
H, br s), 7.15 (1H, d, J _HF = 7.0Hz), 7.92 (1H, d, J _HF = 7.0Hz) p
pm.IR (KBr dsik): 1710,1535,1495,1415,1255cm ^-1 .

Example -8

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Methyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (5.00 g,
22.8 mmol), potassium carbonate (3.89 g, 2
A solution of 8.1 mmol) of acetonitrile (50 ml) was stirred under reflux for 1 hour. Next, cyclopentyl bromide (4.07 g, 27.3 mmol) was added, and the mixture was heated under reflux for 3 hours. After completion of the reaction, the reaction mixture was diluted with 1N hydrochloric acid (10
0 ml) and extracted with ethyl acetate (100 ml × 3 times). The organic layer was washed with water, dried, and then the solvent was distilled off under reduced pressure. The obtained solid was washed with hexane and dried to obtain substantially pure N- (2-fluoro-4-chloro-5).
A white solid (5.56 g, yield 84.7%) of methyl- (cyclopentyloxyphenyl) carbamate was obtained.

Melting point: 120.0 to 123.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.40 to 2.10 (8H, m), 3.77
(3H, s), 4.77 (1H, m), 6.82 (1H, brs), 7.07 (1H, d, J _HF = 10.5H
z), 7.83 (1H, d, J _HF = 7.5Hz) ppm.IR (KBr dsik): 1714,1535,1500,1415,1255,1190cm ^-1 .

Embodiment 9

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Ethyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (1.25 g,
5.69 mmol), potassium carbonate (1.11 g, 8.
03 mmol) and 1-butyn-3-yl p-toluenesulfonate (2.04 g, 9.10 mmol) were added with ethyl alcohol (5 ml) and stirred at 80 ° C. for 1 hour. After completion of the reaction, the reaction mixture was added to 1N hydrochloric acid (50 ml), and extracted with ethyl acetate (50 ml × 3 times). The organic layer was dried and concentrated under reduced pressure, and the obtained solid was washed with hexane and dried to obtain almost pure N- {2-fluoro-4-chloro-5- (1-butyn-3-yl). Light brown solid of ethyl oxyphenyl dicarbamate (1.47
g, yield 90.5%).

Melting point: 109.0-110.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.33 (1 H, t, J = 7.0 Hz), 1.7
0 (1H, d, J = 7.5Hz), 2.51 (1H, d, J = 2.0Hz), 4.23 (2H, q, J = 7.0
Hz), 4.88 (1H, d & q, J = 7.5,2.0Hz), 6.83 (1H, brs), 7.08 (1H,
d, J _HF = 10.0Hz), 8.02 (1H, d, J _HF = 7.5Hz) ppm.

Example -10

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Ethyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (10.0 g,
42.8 mmol) and potassium carbonate (8.87 g, 6
Acetonitrile (150 ml) was added to 4.2 mmol), and the mixture was heated and stirred at 80 ° C. for 1 hour. Next, cyclopentyl bromide (9.57 g, 64.2 mmol) was slowly added thereto, and the mixture was refluxed for 7 hours. After the reaction is completed, 1
N hydrochloric acid (100 ml) and ethyl acetate (100 ml).
× 3 times). After drying the organic layer, the solvent was distilled off under reduced pressure to give almost pure N- (2-fluoro-
Ethyl 4-chloro-5-cyclopentyloxyphenyl) carbamate as a white solid (12.7 g, yield 98.4)
%). The spectrum data is as shown in Example-8.

Example-11

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Methyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (1.25 g,
5.69 mmol) and potassium carbonate (1.17 g,
8.54 mmol), methanol (5 ml) was added, and the mixture was heated under reflux for 2 hours. Then propargyl bromide (1.0
9 g, 8.54 mmol) and heated under reflux for 2 hours.
After completion of the reaction, the reaction mixture was added to 1N hydrochloric acid (50 ml),
The mixture was extracted with ethyl acetate (50 ml × 3 times). The organic layer was dried, concentrated under reduced pressure, and the obtained solid was washed with hexane and dried to obtain almost pure N- (2-fluoro-4).
Methyl-chloro-5-propargyloxyphenyl) carbamate as a white solid (1.32 g, yield 90.0%)
I got

Melting point: 121.0 to 124.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 2.68 (1 H, t, J = 2.0 Hz), 3.7
9 (3H, s), 4.73 (2H, d, J = 2.0Hz), 7.08 (1H, q, J _HF = 10.5Hz),
7.84 (1H, q, J _HF = 7.5Hz) ppm.

Example-12

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Methyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (146 g,
0.66 mol), potassium carbonate (91.7 g, 0.6
Acetonitrile (600 ml) was added to 6 mol) and 1-butyn-3-yl p-toluenesulfonate (149 g, 0.66 mol), and the mixture was heated under reflux for 3 hours. After completion of the reaction, the reaction mixture was poured into 1N hydrochloric acid (1500 ml). The obtained solid was washed with hexane and dried to obtain almost pure N- {2-fluoro-4-chloro-5-
A light brown solid (136 g, yield 85.8%) of methyl (1-butyn-3-yl) oxyphenyl} carbamate was obtained.

Melting point: 78.0 to 80.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.71 (3H, d, J = 6.3 Hz), 2.5
5 (1H, d, J = 1.5Hz), 3.82 (3H, s), 4.92 (1H, d & q, J = 6.3,1.5H
z), 7.15 (1H, d, J _HF = 10.Hz), 8.09 (1H, d, J _HF = 7.5Hz) ppm.

Embodiment 13

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Ethyl N- (2-fluoro-4-chloro-5-hydroxyphenyl) carbamate (6.50 g,
27.8 mmol), potassium carbonate (4.23 g, 3
Acetonitrile (100 ml) was added to 0.6 mmol), followed by stirring at 50 ° C. for 0.5 hour. Then 1-butyne-
3-yl p-toluenesulfonate (3.86 g, 3
(0.6 mmol) and heated under reflux for 4 hours. After completion of the reaction, the reaction mixture was added to 1N hydrochloric acid (100 ml) and extracted with ethyl acetate (100 ml × 3 times). The organic layer was dried and concentrated under reduced pressure to obtain substantially pure ethyl N- {2-fluoro-4-chloro-5- (1-butyn-3-yl) oxyphenyl} carbamate as white crystals (7.67 g). ,
Yield 96.4%). Example of spectral data
As shown in FIG.

Example-14

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Methyl N- (2-fluoro-4-chloro-5-isobutyloxycarbonyloxyphenyl) carbamate (6.00 g, 18.8 mmol), potassium carbonate (2.59 g, 18.8 mmol), a catalytic amount Potassium iodide and cyclopentyl bromide (3.36
g, 22.5 mmol), and the mixture was heated under reflux for 4 hours. After completion of the reaction, the reaction mixture is
Hydrochloric acid (50 ml) and ethyl acetate (50 ml × 3
Times). The organic layer was dried, concentrated under reduced pressure, and the obtained solid was washed with hexane and dried to give almost pure methyl N- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) carbamate in white. A solid (4.94 g, 91.5% yield) was obtained. The spectrum data is shown in Example-8.

Example -15

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Ethyl N- (2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl) carbamate (1.45 g, 4.97 mmol) and potassium carbonate (1.03 g, 7.46 mmol) were added to ethyl alcohol (5 ml). ) And heated under reflux for 2 hours. Then, cyclopentyl bromide (1.11 g, 7.46 mmol) was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the mixture was added to 1N hydrochloric acid (50 ml), and ethyl acetate (50 ml × 3 times) was added.
Extracted. The organic layer was dried, concentrated under reduced pressure, and the obtained solid was washed with hexane and dried to obtain substantially pure ethyl N- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) carbamate in white. Solid (1.
41 g, yield 94.0%). The spectrum data is shown in Example-7.

Example-16

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Methanol (12 ml) was added to methyl N- (2-fluoro-4-chloro-5-isobutyloxycarbonyloxyphenyl) carbamate (5.00 g, 15.6 mmol) and potassium carbonate (3.24 g, 23.4 mmol). ) And heated under reflux for 1 hour. Then, isopropyl iodide (5.32 g, 31.3 mmol) was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction mixture was added to 1N hydrochloric acid (50 ml), and ethyl acetate (50 ml × 3 times) was added.
Extracted. The organic layer was dried, concentrated under reduced pressure, and the obtained solid was recrystallized from ether / hexane to give substantially pure methyl N- (2-fluoro-4-chloro-5-isopropyloxyphenyl) carbamate. A white solid (4.05 g, yield 98.8%) was obtained.

Melting point: 90-93 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.35 (3H, d, J = 6.0 Hz), 3.8
1 (3H, s), 4.53 (1H, sep, J = 6.0Hz), 6.91 (1H, brs), 7.10 (1H,
d, J _HF = 10.5Hz), 7.86 (1H, d, J _HF = 7.5Hz) ppm.

Example 17

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Methyl N- (2-fluoro-4-chloro-5-isobutyloxycarbonyloxyphenyl) carbamate (5.37 g, 16.8 mmol), potassium carbonate (2.32 g, 16.8 mmol) and 3-methyl Cyclopentyl paratoluenesulfonate (5.00
g, 20.2 mmol), and methanol (50 ml) was added thereto, followed by heating and stirring at 85 ° C. for 4 hours. After completion of the reaction, the reaction mixture was added to 1N hydrochloric acid (100 ml), and ethyl acetate (50 ml) was added.
ml x 3). The organic layer is dried and concentrated under reduced pressure,
The obtained solid was washed with hexane to give a substantially pure white solid of methyl N- [2-fluoro-4-chloro-5- (3-methylcyclopentyl) oxyphenyl] carbamate (3.81 g, Yield 75.0%).

¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.02 and
1.08 (total 3H, d, J = 6.0Hz), 1.25 ~ 2.40 (7H, m), 3.77 (3H,
s), 4.75 (1H, m), 6.68 (1H, brs), 7.05 (1H, d, J _HF = 10.5Hz),
7.75 (1H, d, J _HF = 7.5Hz) ppm.

Example-18

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Ethyl N- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) carbamate (1
2.7 g, 42.1 mmol), ethyl alcohol (5
0 ml) and a 2N aqueous solution of sodium hydroxide (100 m
l) was added, and the mixture was stirred and stirred at 110 ° C for 4 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, water (100 ml) was added, and the mixture was extracted with ethyl acetate (100 ml × 3 times). The organic layer is washed with a saturated saline solution, the organic layer is dried and concentrated under reduced pressure, and the obtained solid is washed with hexane to obtain a substantially pure product.
-Fluoro-4-chloro-5-cyclopentyloxyaniline as a colorless transparent oil (9.36 g, yield 96.8).
%).

Boiling point: 143-145 ° C./1.5 mmHg ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.40-2.00 (8H, m), 3.72
(2H, brs), 4.67 (1H, m), 6.39 (1H, d, J _HF = 9.0Hz), 7.04 (1H, m
d, J _HF = 11.0Hz) ppm.IR (neat): 3500,3400,1630,1510,1420,1245,1185cm ^-1 .

Example-19

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N- (2-fluoro-4-chloro-5-
Ethyl (1-butyn-3-yl) oxyphenyl) carbamate (6.56 g, 23.0 mmol), ethyl alcohol (20 ml) and a 2N aqueous solution of sodium hydroxide (50 ml) were added, and the mixture was heated with stirring at 110 ° C. for 4 hours. did. After the reaction was completed, the cooled reaction mixture was poured into ice water, and the precipitated solid was filtered to obtain substantially pure 2-fluoro-4-chloro-5- (1-butyn-3-yl) oxyaniline. White crystals (3.52 g, 16.5 mmo)
1) was obtained. The filtrate was extracted with ethyl acetate (50 ml × 3 times), and the organic layer was dried and then concentrated to obtain the desired product (1.18 g, 5.51 mmol). The yield was 95.8% in total.

Melting point: 74.5-75.5 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.60 (3H, d, J = 6.3 Hz), 2.4
8 (1H, d, J = 1.5Hz), 3.46 (2H, brs), 4.72 (1H, d & q, J = 6.3Hz, J
= 1.5Hz), 6.62 (1H, d, J _HF = 7.5Hz), 7.01 (1H, d, J _HF = 10.0Hz)
ppm.

Example -20

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2-fluoro-4-chloro-5-cyclopentyloxyaniline (2.30 g, 10.0 mmol)
l) in ethyl acetate (25 ml) at room temperature at room temperature, trichloromethylchloroformate (2.00 g, 10.0 m
mol) in ethyl acetate (5 ml) was slowly added dropwise. After completion of the dropwise addition, the mixture was heated to distill off the ethyl acetate, whereby 2-fluoro-4-chloro-5-cyclopentyloxyphenyl isocyanate was obtained almost quantitatively.

¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.50 to 2.10
(8H, m), 4.67 (1H, m), 6.60 (1H, d, J _HF = 7.5Hz), 7.12 (1H, d, J
_HF = 10.5Hz) ppm.IR (neat): 2275,1720,1615,1525,1470,1195cm ^-1 .

Example 21

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2-fluoro-4-chloro-5- (1-butyn-3-yl) oxyaniline (300 g, 1.4 m
ol) in ethyl acetate (1500 ml) at room temperature in trichloromethyl chloroformate (283.9 g, 1.
44 mol) was gradually added dropwise. After completion of the dropwise addition, the mixture was heated to distill off ethyl acetate to obtain a brown solid. Carbon tetrachloride (300 ml) was added to this, and the insoluble urea derivative was filtered off. Then, carbon tetrachloride was distilled off under reduced pressure to give 2-fluoro-4-chloro-5- (1-butyne- 3-yl) oxyphenyl isocyanate (31
5.9 g, 1.32 mol, yield 94.3%).

¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.70 (3H, d,
J = 7.0Hz), 2.51 (1H, d, J = 2.0Hz), 4.78 (1H, d & q, J = 7.0,2.0H
z) .6.90 (1H, d, J _HF = 8.0Hz), 7.19 (1H, d, J _HF = 10.0Hz) ppm.IR (KBr disk): 2300,1615,1525,1465,1195cm ^-1 .

Reference Example- 1

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In a 1 L three-necked round bottom flask, 2-chloro-
4-fluoro-5-cyclopentyloxyphenyl isocyanate (203 g, 0.794 mol) and methyl 2-hydroxy-3-methyl-3-butenoate (110 g,
(0.794 mol) in a solution of ethyl acetate (200 ml) in propylene oxide (20 ml, 16.6 g, 0.1 g).
286 mol) and then triethylamine (8.
0 g, 0.0791 mol) of ethyl acetate (30 ml)
The solution was slowly added dropwise so that the solution temperature became 50 ° C. or lower, and the mixture was stirred at that temperature for 2 hours, and further stirred under heating and refluxing for 2 hours. After completion of the reaction, 1N hydrochloric acid (100 m
l) was added, and the mixture was extracted with ethyl acetate (200 ml × 2 times). The organic layer was dried, and the solvent was distilled off under reduced pressure. Toluene (50 ml) was added, and the mixture was left to stand.
White-yellow solid of N- (2-fluoro-4-chloro-5-cyclopentyloxyphenyl) -5-isopropylidene-1,3-oxazolidine-2,4-dione (201.
7 g, 0.57 mol, yield 72%).

Melting point: 104.5-105.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.58-1.91 (8H, m), 2.00
(3H, s), 2.26 (3H, s), 4.73 (1H, m), 6.77 (1H, d, J _HF = 6.6Hz),
7.27 (1H, d, J _HF = 8.5Hz) ppm. IR (KBr disk): 1820,1743,1693cm ^-1 .

Reference Example- 2

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2-Chloro-4-fluoro-5- (1-butyn-3-yl) oxyphenylisocyanate (2
4.0 g, 0.1 mol) and methyl 2-hydroxy-3-methyl-3-butenoate (14.3 g, 0.11 mol)
l) in ethyl acetate (100 ml), propylene oxide (1 ml) was added, and then triethylamine (1.02 g, 0.01 mol) in ethyl acetate (10 ml) was added.
1) The solution was slowly added dropwise so that the solution temperature did not rise to 50 ° C. or higher, and the mixture was further stirred for 2 hours while heating under reflux. After completion of the reaction, 1N-hydrochloric acid (50 ml) was added, and the mixture was extracted with ethyl acetate (100 ml × 2). The organic layer was dried, the solvent was distilled off under reduced pressure, and the obtained crude product was recrystallized from toluene / hexane to give 3N- {2-fluoro-4-chloro-5- (1-butyne- 3-yl) oxyphenyl} -5-isopropylidene-1,3-oxazolidine-2,4-dione as a white yellow solid (28.71 g,
0.085 mol, yield 85%).

Melting point: 102.0 to 103.0 ° C. ¹ H-NMR spectrum (CDCl ₃ , TMS): δ 1.70 (3H, d, J = 6.0 Hz), 2.0
3 (3H, s), 2.28 (3H, s), 2.52 (1H, d, J = 1.5Hz), 4.80 (1H, d & q,
J = 6.0Hz, 1.5Hz), 7.12 (1H, d, J _HF = 6.0Hz), 7.32 (1H, d, J _HF =
9.0Hz) ppm.IR (KBr disk): 2120,1820,1736,1680,1505,1430,1375,1
200cm ^-1 .

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Emiko Ejiri 5-3-5 Wakamatsu House, Azuma 202, Sagamihara City, Kanagawa Prefecture (72) Inventor Tomoko Tateno 2-32-40 Futamagawa, Asahi-ku, Yokohama-shi, Kanagawa Prefecture (72) Inventor Kiyomi Aizawa 322-11 Unomori, Sagamihara City, Kanagawa Prefecture (72) Inventor Yuichi Onchi 3-27-2 Tatsumidai Higashi, Ichihara City, Chiba Prefecture, Japan No. 504 Examiner Michie Hirayama (56) References JP Sho 63- 41466 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) C07C 271/28 C07C 269/04 CA (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] (1) Formula 1 (In the formula 1, X is .R ¹ represents a halogen atom represents a hydrogen atom, a cycloalkyl group having a carbon number of 3-8, an alkynyl group, or R ³ OCO group having a carbon number of 2 to 5, R ² and R ³
Represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group. R above
Represented by ¹ Resid black alkyl group, A Rukiniru group, a halogen atom, a cyano group, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, alkoxycarbonyl group having 1 to 6 carbon atoms It may be substituted. A phenyl carbamate derivative represented by). 2. Formula 2 (In the formula 2, X represents a halogen atom. R ³ represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group.) 3 ClCOOR ² (Formula 3) (In Formula 3, R ² represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group.) Which is reacted in the presence of a base, (In the formula 4, X represents a halogen atom. R ² and R ³ are
Represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group. A method for producing a phenyl carbamate derivative represented by the formula: 3. Formula 4 in the presence of a base (In the formula 4, X represents a halogen atom. R ² and R ³ are
Represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group. ), Wherein only the carbonate group of the phenyl carbamate derivative represented by the formula (5) is selectively hydrolyzed. (In the formula 5, X represents a halogen atom. R ² represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group.) Production method. 4. Formula 5 in the presence of a base (In the formula 5, X represents a halogen atom. R ² represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group.) Formula 6 R ⁴ —Y (Formula 6) (In Formula 6, R ⁴ is an alkyl group having 1 to 12 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 5 carbon atoms or 2 to 2 carbon atoms. 5 represents an alkynyl group;
^The alkyl group, cycloalkyl group, alkenyl group and alkynyl group represented by ⁴ are a halogen atom, a cyano group, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, and an alkoxycarbonyl having 1 to 6 carbon atoms. May be substituted with a group. Y represents a leaving group. Wherein the compound represented by the formula (7) is reacted with a compound represented by the formula: (In the formula 7, X represents a halogen atom. R ⁴ has 1 carbon atom.
12 alkyl group, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group or an alkynyl group having 2 to 5 carbon atoms having 2 to 5 carbon atoms, the alkyl group represented by R ^4, a cycloalkyl group, an alkenyl The group or alkynyl group may be substituted with a halogen atom, a cyano group, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, or an alkoxycarbonyl group having 1 to 6 carbon atoms. R ² is
Represents an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a phenyl group or a benzyl group. )). 5. Formula 8 (In the formula 8, X represents a halogen atom, Z is .R ⁴ where an amino group or an isocyanate group represents a cycloalkyl group having a carbon number of 3-8, Cie black alkyl group represented by the above R ⁴ is , Halogen atom, cyano group, carbon number 1-4
Alkyl group, alkoxy group having 1 to 4 carbon atoms, 1 carbon atom
And 6 may be substituted with an alkoxycarbonyl group. A) substituted fluorobenzene derivative represented by the formula: