JPH04139162A - Carbamic acid ester derivative and its production - Google Patents

Abstract

NEW MATERIAL:A carbamic acid ester derivative expressed by formula I [R is H, 1-4C alkyl, (substituted) alkyl, alkenyl, alkynyl or cycloalkyl; R' is lower alkyl]. EXAMPLE:2-Fluoro-5-methoxyphenylcarbamic acid methyl ester. USE:A synthetic intermediate for highly active new herbicide. PREPARATION:A compound expressed by formula II is made to react with a compound expressed by formula III (Y is chloride, bromide, iodine, methanesulfonyloxy or paratoluenesulfonyloxy) in the presence of a base to provide the compound expressed by formula I.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to the general formula (1) [wherein R may be substituted with a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a halogen atom, etc. Alkyl group: alkenyl group; alkynyl group; cycloalkyl group,
The present invention relates to a carbamate ester derivative represented by , where Ro represents a lower alkyl group, and a method for producing the same.

The compound of the present invention is a new compound that has not been described in any literature.

[Prior art and its problems] Organic chemicals containing fluorine are compounds that are useful as raw materials for agricultural chemicals, dyes and pigments, liquid crystals, and pharmaceuticals. In particular, various intermediates for organic synthesis of metal compounds having a fluorine atom on an aromatic ring, which are characteristically found in recent highly active new herbicides, have been disclosed. However, these synthetic intermediates are often not easily available in pure form due to contamination with regiointrinsic substances or undesirable reaction yields, and the development of simple and high-yield synthetic methods for these is desirable. It was rare.

The compound of the present invention can be easily synthesized using fluorobenzene or the like, which is easy to produce industrially, as a raw material.The compound of the present invention can be converted into a substance useful in the chemical industry using ordinary organic synthesis techniques.

Furthermore, Japanese Patent Publication No. 63-20,428 and Japanese Patent Application Laid-open No. 511 are herbicides that exhibit high herbicidal activity against weeds at low doses through various easy manipulations and have excellent operability on crops. Publication No. 38,256 and Japanese Patent Application No. 2-187
, 163, the carbamate ester described in JP-A-1-315,305, or the oxazolidinedione-conductor described in JP-A-62-174,055, etc., and the present invention has been accomplished. completed.

As is clear from the above description, an object of the present invention is to provide a novel compound of the aforementioned general formula (I) and a method for producing the same.

[Means for solving problems] The present invention provides the following (1) to (5) has each configuration of Ru.

(1) General formula (1) [wherein R represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen atom, an alkenyl group, an alkynyl group, a cycloalkyl group, ,
Ro represents a lower alkyl group, and a carbamate ester derivative represented by .

(2) A compound represented by the general formula (I!) [wherein Ro represents a lower alkyl group] and the general formula (II+) R-Y
(ITI) [wherein R represents an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen atom, etc.; alkenyl group: alkynyl group; cycloalkyl group; Y represents a chlorine atom, a bromine atom , iodine, a methanesulfonyloxy group or a baratoluenesulfonyloxy group, generally in the presence of a base [wherein R is carbon An alkyl group having 1 to 4 atoms, an alkyl group optionally substituted with a halogen atom, etc.: an alkenyl group; an alkynyl group represents a dichloroalkyl group, and Ro represents a lower alkyl group. ] A method for producing a carboxylic acid engineered stellate conductor shown in the following.

General formula c In the formula, Ro represents a lower alkyl group.The general formula is characterized in that the aniline derivative represented by C is converted into a diazonium salt and then hydrolyzed [wherein Ro represents a lower alkyl group] ] A method for producing a carbamate ester derivative.

(4) General formula (V) [wherein R represents an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen atom, or an alkenyl group; alkynyl group: a cycloalkyl group] General formula (I) characterized by reacting the shown aniline rust conductor with a carbamate agent [wherein R is an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen atom, etc.] Alkenyl group; an alkynyl group represents a dichloroalkyl group, and Ro represents a lower alkyl group.] A method for producing a carbamate ester as described above.

(5) - Formula (■) [In the formula, R represents an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen atom, an alkenyl group, an alkynyl group, a cycloalkyl group. General formula (1) characterized by reacting an isocyanate-recognized conductor represented by the following formula with an alcohol represented by the general formula % () [wherein Ro represents a lower alkyl group] [wherein R represents an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen atom, etc.: an alkenyl group; an alkynyl group, a dichloroalkyl group, and Ro represents a lower alkyl group. manufacturing method.

The configuration and effects of the present invention will be explained in detail below.

Next, the method for producing the compound of the present invention and its production intermediate will be described.

The compound of the present invention can be produced by the following three methods.

Method A (I+) [In the formula, R represents an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen group, an alkenyl group; an alkynyl group, a dichloroalkyl group, and Y represents a chlorine atom. , represents a bromine atom, an iodine atom, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and Ro
represents a lower alkyl group.] That is, -by reacting a compound represented by the formula (I+) with a compound represented by the general formula (m) in an inert solvent in the presence of a base, a compound represented by the general formula (1) is obtained. Carbamate ester derivatives can be obtained.

Solvents that can be used in this reaction include benzene, toluene,
Aromatic hydrocarbons such as xylene, aliphatic hydrocarbons such as hexane and heptane, alcohols such as methanol and ethanol, aprotons such as acetonitrile, acetone, N,N-dimethylformamide, dioxane, tetrahydrofuran, dimethyl sulfoxide, etc. Examples include polar solvents and water.

Bases that can be used in this reaction include inorganic bases such as potassium carbonate, sodium carbonate, magnesium oxide, sodium hydroxide, potassium hydroxide, sodium hydride, and sodium methoxide, or alkali metal alkoxides, triethylamine, trimethylamine, pyridine, and dimethylaniline. Organic bases such as

The reaction temperature for this reaction may be selected from the range of 0°C to the boiling point of the solvent used, and the compound of general formula (I) can be isolated by ordinary post-treatment, but if necessary, it can be recrystallized. Purification methods such as , column chromatography, etc. can also be used.

Further, this reaction may be carried out as a two-phase system reaction using a phase transfer catalyst. In this case, phase transfer promoters that can be used include quaternary ammonium salts such as trioctylmethylammonium chloride and tetraethylammonium bromide;
Examples include crown ethers such as 8-crown-6 and 15-crown-5, and aprotic polar compounds such as N,N-dimethylformamide and dimethyl sulfoxide.

The starting material for this reaction, a compound represented by the general formula (11) [wherein Ro represents the same meaning as above and Ko] can be produced, for example, by the following synthetic route.

(TV) (11) [wherein,
Ro represents the same meaning as above, that is, the general formula (
The aniline derivative represented by rV) is converted into a diazonium salt using sodium nitrite under acidic conditions such as hydrochloric acid, sulfuric acid, or fluoroboric acid, and then hydrolyzed in an acidic solution such as dilute sulfuric acid, dilute hydrochloric acid, or dilute nitric acid. can be converted to the compound (!■) by

The starting material for this reaction, the carbamate ester of general formula (TV), can be easily prepared by the method described in DE 2703113E1.

This reaction is generally carried out entirely in an aqueous solution, but it can also be carried out in the presence of a co-solvent that does not interfere with the progress of the reaction. Co-solvents include acetone, tetrahydrofuran, dimethyl sulfoxide, methanol,
Examples include ethanol.

The reaction temperature in the stage of forming the diazonium salt in this reaction is selected from the range of -20°C to room temperature, and is preferably from 0°C to 15°C for ease of operation.

Further, the reaction temperature at the step of hydrolyzing the diazonium salt in this reaction is selected from a range from 0° C. to the boiling point of the solvent, but a temperature near the boiling point of the solvent is desirable in that the reaction proceeds rapidly.

B method (Vl (
1) [In the formula, R and Ro represent the same meanings as above] That is, the aniline derivative represented by the general formula (V) is reacted with a carbamate-forming agent in the presence of a solvent to form a compound of the general formula (I). compound can be obtained.

The aniline derivative represented by the general formula (V) which is the starting material for this reaction is disclosed in JP-A-62-298.5112, JP-A-60-158,147, [54,006,18
It can be easily prepared by the method described in Patent No. 5 and the like.

Solvents that can be used in this reaction may be those that do not inhibit this reaction, such as aromatic hydrocarbons such as benzene, toluene, and xylene, aliphatic hydrocarbons such as hexane and heptane, diethyl ether, diisopropyl ether, etc. ethers, halogenated solvents such as methylene chloride and chloroform, alcohols such as methanol and ethanol, aprotic polar solvents such as acetonitrile, acetone, N,N-dimethylformamide, dioxane, tetrahydrofuran, dimethyl sulfoxide, and water, etc. can be mentioned.

As a carbamate agent that can be used in this reaction, chlorine 1
! ! Examples include haloformates such as methyl acid and ethyl prothioformate, and carbonic anhydrides such as di-t-butyl dicarbonate.

This reaction may be carried out in the presence of a base if necessary. Bases tested include inorganic bases such as potassium carbonate, sodium carbonate, magnesium oxide, sodium hydroxide, potassium hydroxide, sodium hydride, and sodium methoxide, and organic bases such as alkali metal alkoxides, triethylamine, trimethylamine, pyridine, and dimethylaniline. Bases can be mentioned.

The reaction temperature can be appropriately selected from room temperature to the zero pressure boiling point range of the solvent used.

C method (Vl) (I)
[In the formula, R and R represent the same meanings as above.] That is, by reacting the incyanate rust conductor represented by the formula (Vr) with alcohol, the general formula (
The compound shown by can be obtained.

The isocyanate conductor that is the starting material for this reaction is the B
It can be easily prepared by reacting the aniline conductor, which is a raw material for the process, with phosgene or trichloromethyl chloroformate.

This reaction can be carried out under solvent-free conditions or in a solvent.

When carrying out the reaction in a solvent, any solvent that can be used may be one that does not inhibit the reaction, such as aromatic hydrocarbons such as benzene, toluene, and xylene, aliphatic hydrocarbons such as hexane and heptane, and diethyl. ether,
Ethers such as diisopropyl ether, dioxane and tetrahydrofuran, halogenated solvents such as methylene chloride and chloroform, acetonitrile, acetone, N, N-
Examples include aprotic polar solvents such as dimethylformamide and dimethyl sulfoxide, and water.

Although this reaction proceeds without a catalyst, it may also be carried out in the presence of a small amount of base.

Usable bases include inorganic bases such as potassium carbonate, sodium carbonate, magnesium oxide, sodium hydroxide, potassium hydroxide, sodium hydride, and sodium methoxide, and organic bases such as alkali metal alkoxides, triethylamine, trimethylamine, pyridine, and dimethylaniline. can be mentioned.

The reaction temperature is selected from the range of -20°C to 150°C, but 0°C to room temperature is preferred for operational reasons.

Examples of the present invention and reference examples of synthesizing useful compounds using the compounds of the present invention are shown below, but the present invention is not limited thereto.

Example I Methyl 2-fluoro-5-hydroxyphenylcarbamate (1,0 g 5.4 mm
ol), potassium carbonate (0.5 g), methyl iodide (3
, 8 g) was added thereto, and acetonitrile (30 mj2) was added to dissolve it, followed by stirring under heating under reflux for 2 hours.

After the reaction was completed, water (10 mA) was added to the mixture, and the mixture was extracted with ether (10a+1x3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified by silica gel column chromatography using J! IL separation and purification yielded a pale yellow oil (1,
02g) was obtained.

This product was confirmed to be methyl 2-fluoro-5-methoxyphenylcarbamate by analysis such as 'H-NMR. Yield 95%.

'H-NMRδ (CDC1s, PPM); 3.8
0 (3)1.5).

6.49 (IH, ddd, JHr-4, 58Zj-3
, 6, 9, 9H2).

6.86 (IH, br).

6.96 (IH, dd, J, -10,4Hz, J-
9.3Hz>7.42 (IH, dd, JHW-8,7)
1z, J-2,9Hz) IR, C, o-1740cm
-' Example 2 2-fluoro-5- was added to a 501IlfL eggplant flask.
Methyl hydroxyphenylcarbamate (2.0 g.

10.8 mmol), potassium carbonate (1 g), and isopropylene iodide (9.2 g) were added, acetonitrile (50 mf) was added to dissolve them, and the mixture was stirred under heating under reflux for 2 hours.

After the reaction was completed, water (30mf) was added to the mixture and ether (
20*ILx3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified using silica gel column chromatography to obtain a pale yellow oil (2.2gl).
I got it.

This product was confirmed to be methyl 2-fluoro-5-isopropoxyphenylcarbamate by analysis such as 'H-NMR. Yield 9o%.

' H-NMR δ (CDC1,, PPM) 1.31 (
5)1. d, J-1i, 0)IZ).

3.79 (3H, s).

4.48 (IH, sep, J”6.0Hx).

6.48 (IH, ddd, Jsr-4, 5Hz, J-9
, 0, 3, 1Hz).

6.94 (IH, dd, JH, -10,6H1,J-
9,0H1).

7.72(l)I, dd, JHp-6,8Hz, J-3
, 1Hz) IR; 17C11, -1740C11
-'Example 3 Methyl 2-fluoro-5-hydroxyphenylcarbamate (3.0 g) was placed in a 100 mjl eggplant-shaped flask.

16.2 mmol), potassium carbonate (2.2 g)
, cyclopentyl bromide (5 g) and acetonitrile (30 ft) were added thereto, and the mixture was stirred under heating under reflux for 10 hours.

The resulting reaction mixture was allowed to cool to room temperature, and then extracted with ethyl acetate (20mfLX3). The organic layer was diluted with water (10 Il
lft x 3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a brown oil.

This was isolated and purified using silica gel column chromatography to obtain a pale yellow oil (3,0g).

This is the result of analysis such as 'H-NMR spectrum 2-
It was confirmed that it was methyl fluoro-5-cyclopentyloxyphenylcarbamate. Yield 73%.

1 day NMRδ (CDCI, , PPM); 1.50-2
．． 00 (8H, br).

3.79 (3Ls).

4.72 (l11.m).

8.46 (DI, ddd, J,, r-4, 1) 1z, J
-9.3J, IHz).

6.54~F, 20 (lH, br).

6.94 (1)1. dd, Jsr-10,8)1z,
J-9, 3Hz).

7.70 (IH, dd, J++r-6,8) 1z, J-
3,1Hx) fR; IJc-o-1740Cm-
'Example 4 Methyl 2-fluoro-5-hydroxyphenylcarbamate (1.0 g) was placed in a Somi eggplant flask.

5.4 mmol), potassium carbonate (1.0 g), and propargyl bromide (3.2 g), and acetonitrile (
20si) was added and melted, and the mixture was stirred for 2 hours under heating and reflux.

After the reaction was completed, water (30 sft) was added to the mixture and extracted with ether (20*ILx3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified using silica gel column chromatography to obtain a colorless oil (1gI).
,02g) was obtained.

This product was found to be 2-fluoro-
It was confirmed that it was methyl 5-propargyloxyphenylcarbamate. Yield 85%.

寞) 1-NMRδ (CDCIs, PPM); 2
．． 52 (LH, t, J-2, 48Z).

3.79 (3H, s).

4.86 (2H, dj-2, 4H2).

6.58 (LH, ddd, Jor-4,5) 1m, J-
9,0,3,6H2).

6.99(1)1. dd, J,, r-10,4Hz, J
-9,0Hx).

7.82 (IH, dd, JHr-8, 7Hz, J-2,
9Hz) TR, cycmo-1730ca+-' Example 5 Ethyl 2-fluoro-5-hydroxyphenylcarbamate (1.0 g) was placed in a 50 mj2 eggplant flask.

5.0 mmol), potassium carbonate (1.0 g), and n-hexyl bromide (2.0 g) were added thereto, acetonitrile (50 mj2) was added to dissolve them, and the mixture was stirred under heating under reflux for 4 hours.

After the reaction was completed, water (30 mA) was added to the mixture, and the mixture was extracted with ether (40 mIL x 3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The resulting brown oil was purified using silica gel column chromatography. Purified colorless oil (1.1g
) was obtained.

This product was found to be 2-fluoro-
It was confirmed that it was ethyl 5-n-hexyloxyphenylcarbamate. Yield 78%.

'H-NMRδ (CDC13, PPM): 0.9
0(31(,brt).

x, 3z (an, br).

3.92(2)1. Mt, J-8, 1Hz).

5.48 (IN, ddd, JHp-4, 2Hz, J”3
．． 2,9. IHz).

8.94(1)l, dd, JNP-10,68Z, J-
9.1Hz).

7.73 (IH, dd, JurJ, 9Hz, J=3.2
Hz)-rR; Sycmom1730cm-'Example 6 Isobutyl 2-fluoro-5-hydroxyphenylcarbamate (914 mg
), potassium carbonate (1.0g), methyl iodide (2g
), acetonitrile (20a+J2) was added to dissolve it, and the mixture was stirred under heating under reflux for 4 hours.

After the reaction was completed, water (10 mil) was added to the mixture and extracted with ether (1011ix3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was isolated and purified using silica gel column chromatography to obtain a pale yellow oil (782 mg).
) was obtained.

This product was confirmed to be isobutyl 2-fluoro-5-methoxyphenylcarbamate by analysis such as ')I-NMR. Yield 81%.

') i-NMR5 (CDC1j, PPM).

0.98 (6H, d, J-6, 88x).

199 (1B, tsep, J=6.8, 6.8Hz)
.

3.78 (3)! , s).

3.97 (2)1. d, J-6,8Hz) 6.50(
1)1. ddd, JHy-4, 1H1, J-8, 8, 3
,0H1).

1i, 96 (1)1. dd, J, -8,5Hz, J
-3,0H1).

IR; ν(*0"1730c+o-'Example 7 Methyl 2-fluoro-5-aminophenylcarbamate (940 g, 5a*
ol) and added IN hydrochloric acid (15+l) to dissolve it.

While cooling the solution in a water bath, sodium nitrite aqueous tfI solution (345 g/2vrlt 1 (2Q) was added dropwise.
After the dropwise addition was completed, the mixture was further stirred in a water bath for 5 minutes.

The resulting yellow solution was poured into a boiling aqueous IN sulfuric acid solution,
The mixture was heated under reflux for 15 minutes.

After the reaction was completed, the mixed solution was allowed to cool to room temperature, and ethyl acetate (
3sJl x 3) and dried over anhydrous magnesium sulfate.

This was concentrated under reduced pressure to obtain a brown solid (876B).

This is the result of analysis of l-NMR spectrum etc. 2
It was confirmed that it was methyl -fluoro-5-hydroxyphenylcarbamate. Yield 94%.

' ) l-NMRδ (CDCIl, PPM); 3.
81 (3H, s).

4.68 (IH, s).

6.47 (IH, ddd, JHr-4, 2Hz, J-9
, 1, 3, 2Hz).

6.80-7.2(1(It(,br).

fi, 92 (IH, dd, JHr-IQ, 8H1, J-
9,1H2).

7.72(+)1. dd, JHy-8,9) 1z, J-
3,2)1z).

IR; vc, o-1700cri-'m, p,;
120.2-125.8℃ Example 8 Isobutyl 2-fluoro-5-aminophenylcarbamate (1.8g, 8a*
ol) and added IN hydrochloric acid (3011f) and methanol (5+of) to dissolve it.

Sodium nitrite aqueous solution (
Even after 0 dropwise addition of 570mg15mJl)+201 was completed, the mixture was stirred for 5 minutes in a water bath. The resulting yellow solution was poured into a boiling aqueous IN sulfuric acid solution and heated to reflux for 15 minutes.

After the reaction, the mixed solution was allowed to cool to room temperature, and ethyl acetate 71/
(510J2 X3) and dried over anhydrous magnesium sulfate. This was concentrated under reduced pressure to yield a brown solid (1.2 gl).

This is the result of analysis such as 'H-NMR spectrum 2-
It was confirmed that it was isobutyl fluoro-5-hydroxyphenylcarbamate. Yield 66%.

'H-NMRδ (CDC13, PPM) 0.978 (6
H, d, J = 8.8Hz).

1.99 (IH, dsap, J-6, 5, 6, 8Hz)
.

3.97 (2H, d, J”6.5Hz).

8.47(l)1. ddd, JHr-5,4Hz, J-
9,9,3,6)IZ).

8.80-7.20 (IH, br).

8.92 (IH, dd, JHr-10, 88Z, J-9
,98Z).

7.72 (lH, dd, JHr-6,9Hz, J-3,
6Hz)-■R; Shimilo-1fu05e■-! a
+, p,; 107.1-112.5°C Example 9 2-fluoro-5-methoxyaniline (1.0 g, 7.1+ mmol) in a 50a+J2 eggplant flask,
Potassium carbonate (7ooB), methanol (10mJZ)
was added and stirred at room temperature.

Methyl chloroformate (708 mg) was added dropwise to the mixed solution, and after the addition was completed, the reaction temperature was raised to the reflux point and stirred for 1 hour.

The resulting mixed solution was allowed to cool, IN hydrochloric acid (10 μl) was added, and the mixture was extracted with ethyl acetate (LO×3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified using silica gel column chromatography to obtain a pale yellow oil (1.22 g) of methyl 2-fluoro-5-methoxyphenylcarbamate.
) was obtained.

The spectral data of this product were consistent with those described above.

Yield 86%.

Example 10 2-Fluoro-5-isopropoxyaniline (1.0 g, 5.9 mmol) was placed in a 50 x 1 eggplant-shaped flask.
Potassium carbonate (813a+g) and N,N-dimethylformamide (10 mjl) were added, and the mixture was stirred at room temperature.

Methyl chloroformate (800 mg) was added dropwise to the mixed solution, and after the addition was completed, the mixture was further stirred for 5 hours.

IN hydrochloric acid (10+ajl) was added to the resulting mixed solution, and the mixture was extracted with ethyl acetate (1G+1ILx3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified using silica gel column chromatography to obtain 2-fluoro-
Methyl 5-isopropoxyphenylcarbamate (1,
23g) was obtained.

The spectral data of this product were consistent with those described above.

Yield 92%.

Example 11 2-Fluoro-5-propargyloxyaniline (1,0 g, 6.1 mmo
l) , IN aqueous sodium hydroxide solution (10 i),
Methanol (10+aIL) was added and the mixture was stirred at room temperature.

Methyl chloroformate (600a+g) was added dropwise to the mixed solution, and after the addition was completed, the mixture was further stirred for 5 hours.

IN hydrochloric acid (10mj2) was added to the obtained mixed solution, and the mixture was extracted with ethyl acetate (10mflx3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified using silica gel column chromatography to obtain a pale yellow oil of methyl 2-fluoro-5-propargyloxyphenylcarbamate (
1.22g) was obtained.

The spectral data of this product were consistent with those described above.

Yield 90%.

Example 12 2-fluoro-5-cyclopentyloxyaniline (1.0 g, 5.1 mmol
), IN aqueous sodium hydroxide solution (lhi), and methanol (10s+j2) were added, and the mixture was stirred at room temperature.

Methyl chloroformate (503 mg) was added dropwise to the mixed solution, and after the addition was completed, the mixture was further stirred for 5 hours.

IN salt fi(lo+*j2) was added to the resulting mixed solution and extracted with ethyl acetate (10mj2 x 3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified using silica gel column chromatography to obtain a colorless oil of methyl 2-fluoro-5-cyclopentyloxyphenylcarbamate (
1.1 g) was obtained.

The spectral data of this product were consistent with those described above.

Yield 85%.

Example 13 2-fluoro-5-n-hexyloxyaniline (1.0 g, 4.7 gmo
1), IN aqueous sodium hydroxide solution (5■i), and methanol (10■J2) were added, and the mixture was stirred at room temperature.

Ethyl chloroformate (520 mg) was added dropwise to the mixed solution, and after the addition was completed, the mixture was further stirred for 8 hours. IN hydrochloric acid (10sIL) was added to the resulting mixed solution, and ethyl acetate (10sIL) was added to the resulting mixed solution.
1x3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained brown oil was purified using silica gel column chromatography to obtain a yellow oil of ethyl 2-fluoro-5-n-hexyloxyphenylcarbamate (91i8+ig).

The spectral data of this product were consistent with those described above.

Yield 75%.

Example 14 2-fluoro-5-methoxyphenylisocyanate (10 g, B, O mol) was added to a 50 mA eggplant flask.
), and toluene (10'+ej2) was added to dissolve it. While stirring at room temperature, add methanol (0,
2+ejl) was added dropwise.

After the dropwise addition was completed, the reaction mixture was further stirred at room temperature for 1 hour, then IN hydrochloric acid (2a+f) was added, and ethyl acetate (2a+f) was added.
mjl x3).

The organic layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give a colorless oil (1.19 g).
-Methyl-fluoro-5-methoxyphenylcarbamate was obtained.

The spectral data of this product were consistent with those described above.

quantitative.

Example 15 2-fluoro-5-isopropoxyphenylisocyanate (1,Qgs, 1g
mol) and added toluene (lhjl) to dissolve it. While stirring at room temperature, add methanol (0
, 2 liters) was added dropwise.

After the dropwise addition was completed, the reaction mixture was further stirred at room temperature for 1 hour, then IN hydrochloric acid (2a+42) was added, and ethyl acetate (
2 × 3) extraction.

The organic layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give a colorless oil (1.14 g).
Methyl fluoro-5-isopropoxyphenylcarbamate was obtained.

The spectral data of this product were consistent with those described above.

Yield 98%.

Example! 6 Add 2-fluoro-5-cyclopentyloxyphenyl isocyanate (1,0 g) to a 50III eggplant flask.
.

4.5 gmol) was added thereto, and methanol (+mfL) was added dropwise while stirring at room temperature.

After the dropwise addition was completed, the reaction mixture was further stirred at room temperature for 1 hour, and excess methanol was distilled off under reduced pressure to obtain a colorless m-like substance (1
, 14 g) of methyl 2-fluoro-5-cyclopentyloxyphenylcarbamate was obtained.

The spectral data of this product were consistent with those described above.

quantitative.

Example 1 2-fluoro-5-n-hexyloxyphenyl isocyanate (1,0
g, 4.2 mwol) was added thereto, and ethanol (0.2 i) was added dropwise while stirring at room temperature.

After the dropwise addition was completed, the reaction mixture was further stirred at room temperature for 1 hour, and excess ethanol was distilled off under reduced pressure to give a pale yellow oil (1
, 19 g) of ethyl 2-fluoro-5-n-hexyloxyphenylcarbamate was obtained.

The spectral data of this product were consistent with those described above.

quantitative.

Example 18 50+aj! 2-fluoro-5-propargyloxyphenylisocyanate (1.0 g) in an eggplant-shaped flask.

6.6 mmol) was added thereto, and toluene (LOA+IL) was added to dissolve it. Ethanol (D, 2si) was added dropwise to this while stirring at room temperature.

After the dropwise addition was completed, the reaction mixture was further stirred at room temperature for 1 hour, then IN hydrochloric acid (2 ml) was added, and ethyl acetate (2 ml) was added.
j2 x3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain methyl 2-fluoro-5-propargyloxyphenylcarbamate as a colorless oil (1.47 g).

The spectral data of this item does not match the one mentioned above.
quantitative.

Example 19 2-Fluoro-5-methoxyphenylisocyanate (1.0 g, 6.0a + mo
1), triethylamine (10 mg) was added, and toluene (1011J2) was added to dissolve it. Isobutanol (0.5si) was added dropwise to the mixture while stirring at room temperature.

After the dropwise addition was completed, the reaction mixture was further stirred at room temperature for 1 hour, then 1N hydrochloric acid (2si) was added, and ethyl acetate (2s
i x3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain isobutyl 2-fluoro-5-methoxyphenylcarbamate as a colorless oil (1.45 g).

The spectral data of this product were consistent with those described above.

quantitative.

Reference Example 1 2-fluoro-5-methoxyaniline (282 mg, 2.0 mmol) was placed in a 50 mA eggplant-shaped flask,
Dissolved in ethyl acetate (2si). While stirring the solution at room temperature, add trichloromethyl chloroformate (0,
2 mL) was added dropwise.

The reaction solution was further raised to reflux temperature and stirred for 30 minutes, and then the solvent was distilled off. Carbon tetrachloride was added to the obtained residue and allowed to cool. After removing the precipitated solid, the resulting solution was concentrated under reduced pressure to obtain a pale yellow oil (323+ag).

This is ') I-NMR spectrum, etc. analysis result 2
-Fluoro-5-methoxyphenylisocyanate was confirmed. Yield 97%.

'H-NMRδ (CDC1s, PPM); 3.7
6 (38,s).

6.53-6.75 (2H, ■).

7.03 (LH, ddd, JHr・9.9Hz, J-
1, 11, 7, 2Hz) IR, Nco'2270cI
ll-1 Reference Example 2 2-Fluoro-5-isoprofoxynaniline (588 mg, 3.5 m+*ol) was placed in a 50 mj2 eggplant flask.
) and dissolved in ethyl acetate (10ei). While stirring the solution at room temperature, trichloromethyl chloroformate (0.4 mjN) was added dropwise.

The reaction solution was further raised to reflux temperature and stirred for 30 minutes, and then the solvent was distilled off. Carbon tetrachloride was added to the resulting residue and allowed to cool.

After removing the precipitated solid, the resulting solution was concentrated under reduced pressure to obtain a pale yellow oil (S85 mgl).

This product was confirmed to be 2-fluoro-5-isopropoxyphenylisocyanate as a result of analysis such as 'H-NllIR spectrum. quantitative.

'H-NMRδ (CDC1,, PPM).

1.30 (6Ld, J-5,98ri.

4.42 (IH, sep, J-5, 9Hz).

6.51-6.73 (2H, m).

7, old (LH, ddd, JMy-9, 9Hz, J-8,
1,2,7Hz)IR; VNCO-2270CI
-'Reference Example 3 2-Fluoro-5-cyclopentyloxyaniline (851 g, 4.4 m
@ol) was added and dissolved in ethyl acetate (10 mj).

While stirring the solution at room temperature, trichloromethyl chloroformate (0.6 sJl) was added dropwise.

The reaction solution was further raised to reflux temperature and stirred for 30 minutes, and then the solvent was distilled off. Carbon tetrachloride was added to the obtained residue and allowed to cool.

After removing the precipitated solid, the resulting solution was concentrated under reduced pressure to obtain a pale yellow oil (8771 g).

This is the result of analysis such as 'H-NMR spectrum 2-
It was confirmed that it was fluoro-5-cyclopentyloxyphenyl isocyanate. Yield 90%.

'H-NMRδ (CDC1,, PPM).

1.50-2.10 (8H, br) 4.68 (IH, br).

6.50-B, 72(2)1. ugly).

7.00 (LH, ddd, JHy-9, 98x, J-1
,8,8,1)1z)IR, Cisco=2270cm-
' Reference Example 4 2-fluoro-5-n-hexyloxyaniline (510 mg, 2.4 m+
ool) and dissolved in ethyl acetate (20ml). While stirring the solution at room temperature, trichloromethyl chloroformate (0.5 g) was added dropwise.

The reaction solution was further raised to reflux temperature and stirred for 30 minutes, and then the solvent was distilled off. Carbon tetrachloride was added to the resulting residue and allowed to cool.

After removing the precipitated solid, the resulting solution was concentrated under reduced pressure to obtain a pale yellow oil (565 mg).

This is the result of analysis such as 'H-NMR spectrum 2-
It was confirmed that it was fluoro-5-n-hexyloxyphenyl isocyanate. quantitative.

'H-NMRδ (CDC1s, PPM); 0.61
11~1.12 (3H,br)1.00~1.50(
8H, br).

3.86 (2H, brt, J-8, 4Hz).

6.51-6.72(2)14).

6.98 (IH, ddd, J++r-9,5) 1z, J
-1■R; shiHco-2270cm-'8.8. I
Hz) Reference Example 5 2-Fluoro-5-propargyloxyaniline (351B, 2.1 mmo
1) and dissolved in ethyl acetate (10 mA). While stirring the solution at room temperature, trichloromethyl chloroformate (0.2 J2) was added dropwise.

The reaction solution was further raised to reflux temperature and stirred for 30 minutes, and then the solvent was distilled off. Carbon tetrachloride was added to the resulting residue and allowed to cool. After removing the precipitated solid, the resulting solution was concentrated under reduced pressure to obtain a pale yellow solid (3891 g).

This product was confirmed to be 2-fluoro-5-propargyloxyphenylisocyanate as a result of analysis such as 'H-NklR spectrum. Yield 97%.

') I-NMRδ (CDI: 1s, PPM): 2.
53 (IH, t, J-2, 4Hz).

4.83 (2H, d, J-2, 4Hz).

6.64-6.84 (2H, l).

6.93~7.16 (IH, Zen) IR, SINl:l+-2270CIl-'Maro, p...
38.1-39.5°C Reference Example 6 Methyl 2-fluoro-5-methoxyphenylcarbamate (592 mg) was placed in a 50 mj2 eggplant flask.

Water (20a+I
Ll was added and extracted with ether (20ml x 3).

The organic layer was washed with water (10ml x 3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a brown oil (
294a+g) was obtained.

This is the result of analysis such as 'H-NMR spectrum 2
-Fluoro-5-methoxyaniline was confirmed. Yield 69%.

'H-NMRδ (CDCIs, PPM); 3.72
(3)1. s) 6.18 (IH, ddd, JHy-2, 7Hz, J-
9,0,3,6Hz)8.34(IH,dd,JHr-
8,1Hz, J-3,61(z).

6.86 (1M, dd, JHy-9, 9Hz, J-9
, 0Hz) IR; 3480, 3370, 1630
, 1520.1210co+-' Reference Example 7 2-Fluoro-5-
Methyl isobropoxyphenylcapamate (801 mg
.

3.5 mmol), ethanol (10 tIL) and 2
Aqueous N sodium hydroxide solution (10 i) was added, and the mixture was stirred under heating under reflux for 2 hours.

Water (201J2) was added to the reaction mixture, and ether (2
0aILx3). The organic layer was diluted with water (10+*1X
3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a brown oil (604 mg).

As a result of analysis such as J-NMR spectrum, this product was confirmed to be 2-fluoro-5-isopropoxyaniline. Quantitative 'H-NMRδ (CDC13, PPM); 1.28
(6H, d, J-8, 4Hz).

3.87 (2H, br).

4.39 (IH, sep, J-8, 41(z)6.1
8(1M, ddd, J, +2-3.61(z, J-2,
7,9,0)1x).

6.32 (IH, dd, J++r-7, 2Hz, J-2
,7Hz)6.85(IH,dd,Jor-10,48
Z, J-9,0Hz)IR; 3470,3380
．． 2!1B0.164s, 1520 1205cm-'
Reference Example 8 Methyl 2-fluoro-5-cyclobentyloxyphenylcabamate (3,0
g, 11.8 ■■ ol), ethanol (50 ■i) and a 2N aqueous sodium hydroxide solution (10 wft) were added, and the mixture was stirred under heating under reflux for 2 hours.

Water (20 + ai) was added to the reaction mixture, and ether (20
aILx3). The organic layer was washed with water (tomJ2
3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a brown oil (2.3 g).

This is the result of analysis such as 'H-NMR spectrum 2-
It was confirmed that it was fluoro-5-cyclopentyloxyaniline. quantitative.

'H-NMRδ (CDCIs, PPM); 1.5
0-2.00 (8)1. br).

3, as (2H, br).

4.63 (IH4).

6.18 (LH, ddd, JHr-4, 5Hz, J8
．． 9,3.6Hx).

6.28 (IH, dd, J, -8,1Hz, J・3
．． 6) 1x).

6.84 (1)1. dd, Jor-11, HIz, J
-8,9)1z)IR; 3470,3380.29
60,1635,1515,1205c ■-1 Reference Example 9 Methyl 2-fluoro-5-probargyloxyphenylcabamate (550 mg
.

Water (20 mj!) was added to the reaction mixture, and ether (2 mj!) was added to the reaction mixture.
0+efLx3). The organic layer was soaked in water (tomj!
After washing with X3), drying with anhydrous magnesium sulfate,
Concentration under reduced pressure gave a brown oil.

This was purified using silica gel column chromatography to obtain a white solid (270 mg).

As a result of analysis such as J-NMR spectrum, this product was confirmed to be 2-fluoro-5-propargyloxyaniline. Yield 65%.

') I-NMRδ (CDCIs, PPM); 2.5
02 (IH, t, J-2, 48Z).

3.72 (28,br).

4.5!1(2)1. d, J-2,4Hz).

6.26 (IH, ddd, JHF-3, 6) 1z, J-
3, 1, 8, 7Hz).

6.39 (LH, dd, Jsr-7, 1Hz, J-3,
1Hz).

6.88 (IH, dd, IH4-10,8Hz, J-8
,78Z)IR; 347G, 3380.29B0,
1635, 1515.1205cm-'I1. p,;
59.2-61.8°C Reference Example 10 Isobutyl 2-fluoro-5-methoxyphenylcabamate (591 mg) was placed in a 50+eIl eggplant flask.

2.5 mmol), methanol (10 mj and 2N
An aqueous sodium hydroxide solution (10+af) was added, and the mixture was stirred for 2 hours under heating and reflux.

Water (20 mA) was added to the reaction mixture, and ether (20 mA) was added to the reaction mixture.
+aj! x3).

The organic layer was washed with water (10+Ij2X3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 2-fluoro-5-methoxyaniline as a brown oil (3071 g
) was obtained.

The results of this analysis were consistent with those described above. Yield 8
7%.

Reference Example 11 2-fluoro-5-cyclopentyloxyaniline (175 mg, 0.9 mmo
1) and 3,4,5.8-tetrahydrophthalic anhydride (15 hg) were added and dissolved in acetic acid (2+al). This mixture was stirred for 2 hours while heating under reflux.

The resulting reaction solution was allowed to cool to room temperature, and water (15 mj2) was added.
was added and extracted with ethyl acetate (lomfLX3). The organic layer was washed with water (5vrlL x 3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a yellow oil (
42011 g) was obtained.

Immediately imitate this using silica gel column chromatography.
It was obtained as a colorless oil (285 g).

'As a result of analysis such as H-NMR spectrum, this product is N-
(2-fluoro-5-cyclopentyloxyphenyl)
It was confirmed that it was -3,4,5,6-tetrahydrophthalimide. Yield 87%.

'H-NMRδ (CDCh, PPM): 1.50~
2.10 (12H, br) 2.43 (4H, br) 4.68 (I)l, s).

6.66-7. f9 (3t(, +glTR; V
c-o 1720(:l-'Reference Example 12 2-fluoro-5-isopropoxyaniline (1.7 g, 10.0!111
101) and 3,4.56-tetrahydrophthalic anhydride (1.7 g) were added and dissolved in acetic acid (30 mft).

This mixture was stirred for 2 hours while heating under reflux. The resulting reaction solution was allowed to cool to room temperature, water (100 mJ2) was added, and the mixture was extracted with ethyl acetate (30 mJ2 X3).

The organic layer was washed with water (5H11℃ x 3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a yellow oil (
420 mg) was obtained.

This material was purified by silica gel column chromatography.
The product was purified to give N-(2-fluoro-5'-isopropoxyphenyl)-3,4,5,6-tetrahydrophthalimide as a colorless oil (2.7 g).The analytical results were consistent with known data. . Yield 90%.

Reference Example 13 N-(2'-fluoro-5'-cyclopentyloxyphenyl)-3,4,5,6-tetrahydrophthalimide (200 mg, 0.6 mmol) and dicyclohexylamine (8 mg) were placed in a Nejiro test tube, and tetrachloroethylene ( 2 ml) was added and dissolved.

Add sulfuryl chloride (102B) to this and heat at 80℃ for 2 hours.
After cooling the reaction solution that had been stirred for an hour, chloroform (
1+Jl) was added and washed with water (0.5ml x 3).

The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a pale yellow solid (218 mg).

This product was confirmed to be N-(2'-fluoro-4-chloro-5'-cyclopentyloxyphenyl)-3,4,5,6-tetrahydrophthalimide as a result of analysis such as ')l-NMR spectrum. . quantitative.

') l-NMRδ (CDCl2.PPM); 1.5
0 to 2.10 (12H, br).

2.43 (4H, br).

4.74 (IH4).

6.77 (IH, d, JHy-6, 7H2).

7.24 (IH, d, J, -94Hz) IR;
y, 0 1725cm-'tr,p,; 74
．． 2-78.0°C Reference Example 14 2-Fluoro-5-methoxyphenylisocyanate (204 mg, 1.2
mmol) and methyl 2-hydroxy-3-methyl-3-butenoate (178 mg), and added toluene (30 mmol) and methyl 2-hydroxy-3-methyl-3-butenoate (178 mg).
l) was added and dissolved.

While stirring this solution at room temperature, triethylamine (1
6 mg) was added dropwise, and after further stirring at room temperature for 30 minutes, IN
Hydrochloric acid (5IIf) was added.

This was extracted with nityl (lomJl x 3), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained yellow oil was purified using silica gel column chromatography to obtain a colorless oil (284 mg).

As a result of analysis such as 'H-NMR spectrum, this product was found to be l-methoxycarbonyl-2-methyl-2-propenyl (2
It was confirmed that it was ゛-fluoro-5-methoxyphenyl) carbamate.

Yield 80%.

') I-NMRδ (CDC13, PPM); 1
．． 84 (3H, br, s).

3.77 (3) 1. s).

3.80 (38,s).

5.15 (1) 1. br).

5.24 (IH, br).

5.50 (ILbrs).

6.52 (IH, ddd, JHr-4, 58x, J-
3,6,9,0Hz).

6.97(1)1. dd, Jsr-10,5Hz, J-
9.0Hxl.

7.04 (LH, br).

7.70 (1)1. dd, J, -7,2H2,J-
3,68Z)TR, νauto 1740.182
5c+e-' Reference Example 15 2-fluoro-5-isopropoxyphenylisocyanate (2911a+g) was placed in a 50 ml eggplant-shaped flask.

1.5 mmol) and 2-hydroxy-3-methyl-
Methyl 3-butenoate (219a+g) was added and dissolved in toluene (30 mfl).

This mixture was stirred at room temperature while triethylamine (
21 mg) was added dropwise, and after further stirring at room temperature for 30 minutes,
N-hydrochloric acid (5mj2) was added.

This was extracted with ether (10+3 in u2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained yellow oil was purified using silica gel column chromatography to obtain a colorless oil (38g.g).

This is the result of analysis such as 'H-NMR spectrum 1-
Medoxycarbonyl-2-methyl-2-propenyl (2
It was confirmed to be '-fluoro-5''-isopropoxyphenyl) carbamate. Yield 80%.

'H-NMRδ (CDC13, PPM); 1.3
0 (6H, d, J-6, 28Z).

1.84 (3H, brs).

3.80 (38,s).

4.47 (IH, sep, J-6, 21(z).

5.15 (IH, br).

5.24 (IH, br) 5.50 (IH, brs).

8.51 (1)1. ddd, JHF-4, 5H2, J
-3,8,9,0H2).

6.95 (IH, dd, J,, r-10,58x, J
-9,0)1z)7.02(DI,br).

7J9 (1)1. dd, Joy-Fi, 8Hz, J-
3,6Hz) IF, ν(,. 1740.
+620cl' Reference Example 16 2-fluoro-5-cyclopentyloxyphenyl isocyanate (877ml) was placed in a 100++l eggplant-shaped flask.
g, 4.0g++1ol) and 2-hydroxy-3
- Add methyl-3-butenoate (650 mg),
Toluene (50 mJZ) was added and dissolved.

While stirring this solution at room temperature, triethylamine (5
3 mg) was added dropwise, and after further stirring at room temperature for 30 minutes, IN
Hydrochloric acid (10 wIl) was added. This is ether (30i
After extraction with u x 3), it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

The obtained yellow oil was purified using silica gel column chromatography to obtain a colorless oil (1.14 g).

This is ') I-NMR spectrum analysis result 1
-methoxycarbonyl-2-methyl-2-propenyl (
2°-fluoro-5-cyclopentyloxyphenyl)
It was confirmed that it was a carbamate. Yield 81%.

') l-NMRδ (CDC1s, PPM): 1.5
0-2.10 (11 Lbr).

3, [1O(38,s).

4.69 (II(, brl.

5.15 (IH, br).

5.24 (IH, br).

5.50 (IH, brs).

6.48(IH,ddd,J,,-4,5)1x,J・
2.9, 9.1Hz).

6.95 (18, dd, Jnr-10, 68Z, J-9
, IHz).

7.08 (IH, br).

7.68 (1M, dd, JHF-6,8Hz, J-2
,9Hz)IR; v cso 1740,1
620cm-'Reference Example 17 2-fluoro-5-n-hexyphenylisocyanate (330B) was placed in a 100ml eggplant-shaped flask.

1.4 mmol) and 2-hydroxy-3-methyl-
Add methyl 3-butenoate (180 mg) and add toluene (
10 wN) was added and dissolved.

While stirring this solution at room temperature, triethylamine (8
11g) was added dropwise, and after further stirring at room temperature for 30 minutes, IN
Hydrochloric acid (2μIL) was added. This is ether (5Il)
After extraction with lItx3), it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

The obtained yellow oil was purified using silica gel column chromatography to obtain a colorless oil (140 IIg).

As a result of analysis such as J-NMR spectrum, this product was confirmed to be 1-methoxycarbonyl-2-methyl-2-propenyl (2'-fluoro-5'-cyclopentyloxyphenyl) carbamate. Yield 27%.

'H-NMRδ (CDCIs, PPM): 0.9
0(3H,br).

1.32 (8) 1. br).

1.84 (3H, brs).

3.79 (3) 1. Sl.

3.90(2)1. brt, J-8, 28x).

5.15 (lH, br).

5.24 (IH, br).

5.49 (IH9brs) 6.50 (IH, ddd, JHr-4,5Hz, J-2
,9,9,1Hz)6.95 (IH,dd,JHr-
10,4Hz, J-9,1)1z)7.09 (l)I
,br).

7.69 (ILdd, J,,r-8,7)1z,J”
2.9Hz) IR; V c-=0 1740,1
820cm-' Reference Example 18 2-Fluoro-5-propargyloxyphenylisocyanate (150+mg) was placed in a 25mu eggplant-shaped flask.

0.8+mmol) and methyl 2-hydroxy-3-methyl-3-butenoate (102 mg) were added, and toluene (Smj2) was added to dissolve them.

While stirring this solution at room temperature, triethylamine (a
B) was added dropwise, and after further stirring at room temperature for 30 minutes, IN hydrochloric acid (1 mjl) was added.

This was extracted with ether (5mux:l), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained yellow oil was purified using silica gel column chromatography to obtain a colorless oil (177 mg).

This is the result of analysis such as 'H-NMR spectrum 1
-methoxycarbonyl-2-methyl-2-propenyl (
It was confirmed that it was 2-fluoro-5'-propargyloxyphenyl) carbamate. Yield 69%.

') I-NMR6 (CDCIs, PPM); 1.8
4 (31(,brs).

2.52 (IH, t, J-2,3Hz).

3.79 (3H, s).

5.65(2H,d,J-2,3)IZ).

5.15 (IH, br).

5.24 (II (, br).

5.50 (IH, brs).

6.80 (IH, ddd, J, r-4, 5Hz, J-3
, 1, 9, 3Hz).

7.99 (11(, dd, Jur-10,6Hz, J-
9,38Z).

7.19 (IH, br).

7.78 (IH, dd, JHr-6, 714Z, J-3
, IH2) IR, νago 174G, 1[12(
lc+m-'cmc 2120cm-'+a,p,; 1B8.1-170.5°C Reference Example 1
9 1-methoxycarbonyl-2-methyl- in a screw cap test tube
2-propenyl (2°-fluoro-5°-methoxyphenyl) carbamate (7.9 mg, 0.03 m+ao
1), dicyclohexylamine (1 mg), tetrachloroethylene (0.5 mf) and sulfuryl chloride (8 mg) were added, heated to 80°C and stirred for 2 hours.

After the reaction was completed, the mixture was washed with water and concentrated under reduced pressure to obtain a pale yellow viscous substance (7,4a+g).

This is the result of analysis such as 'H-NMR spectrum.
-methoxycarbonyl-2-methyl-2-propenyl (
It was confirmed that it was 2-fluoro-4°-chloro-5°-methoxyphenyl) carbamate. Yield 84%.

'H-NMRδ (CDC1s, PPM); 1.8
5 (3H, brs).

3.81 (3H, s).

3.88 (3t(,s).

5.18 (IH, br).

5.25 (1Lbr).

5.50 (ILbrs).

7.07 (1) 1. br).

7.14 (IH,d,J,,-10,4)IZ)7.
82 (IH, d, J, r-7, 5Hz) TR, νcs
o 1740. +620co+-'Reference Example 20 1-methoxycarbonyl-2-methyl- in a screw cap test tube
3-propenyl (2-fluoro-5°-cyclopentyloxyphenyl) carbamate (107 mg.

0.3 mmol), dicyclohexylamine (7 g)
, tetrachloroethylene (2IIIt) and sulfuryl chloride (100 mg) were added, heated to 80°C, and stirred for 2 hours.

After the reaction was completed, the mixture was washed with water and concentrated under reduced pressure to obtain a pale yellow viscous substance (102+ig).

This is the result of analysis such as 'H-NMR spectrum 1
-methoxycarbonyl-2-methyl-2-propenyl (
It was confirmed that it was 2'-fluoro-4'-chloro-5-cyclopentyloxyphenyl) carbamate. Yield 69%.

'H-NMRδ (CDC1s, PPM); 1.4
0 to 2.18 (IIH, br).

3.81 (3H, s) 4.79 (lH, br).

5.16 (IH, br).

5.22 (IH, br) 5.50 (IH, brs).

7.06 (1u, br).

7.09 (IH, d, Joy-9, 4Hz) 7.79 (
IH, d, JHr-7,5Hz) IR; νcllo
1740,1820cm-'Reference Example 21 1-Methoxycarbonyl-2-methyl- in a screw cap test tube
2-propenyl (2'-fluoro-5'-n-hexyloxyphenyl) carbamate (120 mg.

0.326a+mol), dicyclohexylamine (7
(g), tetrachloroethylene (1sj2) and sulfuryl chloride (100 mg) were added, heated to 80°C and stirred for 2 hours.

After the reaction was completed, the mixture was washed with water and concentrated under reduced pressure to obtain a pale yellow viscous substance (127ag).

This is the result of analysis such as 'H-NMR spectrum!
-methoxycarbonyl-2-methyl-2-propenyl (
It was confirmed that it was 2'-fluoro-4'-chloro-5'-n-n-hexyloxyphenyl) carbamate. Yield 97%.

'H-NMRδ (CDC1,, PPM).

0.90 (3H, br).

IJ5 (8) 1. br).

1.85 (3H, br).

3.80 (3H, s).

4.00 (2H, brt, J-6, 88x).

5.16 (IH, br).

5.25 (IH, br).

5.50(1)1. brs).

7.11 (IH, br).

7.12 (IH, d, J,, r-10,41(z).

7.79 (18,d,J,,-7,9Hz)IR:
Vc-a 1740,1610co-'Reference Example 22 1-methoxycarbonyl-2-methyl- in a screw cap test tube
2-propenyl (2°-fluoro-5-propargyloxyphenyl) carbamate (177B.

0.55 mmol), dicyclohexylamine (7a
+g), tetrachloroethylene (5+*jZ) and sulfuryl chloride (150 mg) were added, heated to 80°C and stirred for 2 hours. After the reaction was completed, the mixture was washed with water and concentrated under reduced pressure to obtain a pale yellow viscous substance. Obtained.

This product was further recrystallized from ethanol to form a white solid (
1511Ig) was obtained.

This is the result of analysis such as 'H-NMR spectrum! −
Methoxycarbonyl-2-methyl-2-propenyl (2
It was confirmed that it was (fluoro-4°-chloro-5°-propargyloxyphenyl) carbamate.

Yield 77%.

'H-NMRδ (CDC1s, PPM); 1.87
(3H, brs).

2.59 (IH, t, J-2,4Hz).

3.80 (3H, s).

4.78 (2H, d, J-2,4Hz).

5.15 (IH, br).

5.26 (Hl, br).

5.50 (IH, brs).

7.17 (IH, d, J, -10,4Hz).

7.26 (IH, br).

7.95 (IH, d, JH, -7,38Z)IR;
v c,, 1740.1820cm-'v
csc 2120cm-' Reference Example 23 1-methoxycarbonyl-2-methyl-2-propenyl (2'-fluoro-4°
-Chloro-5°-cyclopentyloxyphenyl)carbamate (193 g, 0.5 mmol), potassium carbonate (34 mg) and acetonitrile (10 mu) were added, and the mixture was stirred at room temperature for 5 hours.

After the reaction was completed, IN hydrochloric acid (21ft) was added, and the mixture was extracted with ethyl acetate (2miX3). The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a yellow oil. This was recrystallized from ethanol as a white solid (170
mg) was obtained.

This is the result of analysis such as 'H-NMR spectrum 3-
It was confirmed that it was (2-fluoro-4'-chloro-5-cyclopentyloxyphenyl)-5-isopropylidene-1,3-oxazoxine-2,4-dione. Yield 96%.

'H-NMRδ (CDI: 1., PP connection); 1.45
~2.10 (8H, br).

2.06 (3H, s).

■R; m, p,; 2.29 (3H1s).

4.72 (1) 1. br).

6.84(it(,d,J,-8,1Hz).

7.29 (IH, d, JH, -9, 1) IZ) νCll
0 1820.1745cm-'98.3~100.1
℃ or less

Claims (5)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkyl group that may be substituted with a halogen atom, etc. group; alkenyl group; alkynyl group; cycloalkyl group;
R' represents a lower alkyl group. ] A carbamate ester derivative represented by: (2) General formula (II) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (II) [In the formula, R' represents a lower alkyl group. ] and the general formula (III) RY(III) [wherein R is an alkyl group having 1 to 4 carbon atoms, an alkyl group optionally substituted with a halogen atom, etc.; alkenyl group; alkynyl group ; represents a cycloalkyl group; Y represents a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group or a para-toluenesulfonyloxy group; General formula (I), which is characterized by reacting with a compound represented by It represents an alkyl group, an alkyl group optionally substituted with a halogen atom, an alkenyl group, an alkynyl group, a cycloalkyl group, and R' represents a lower alkyl group. ] A method for producing a carbamate ester derivative. (3) General formula (IV) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (IV) [In the formula, R' represents a lower alkyl group. ] General formula (II) characterized in that the aniline derivative represented by the formula is converted into a diazonium salt and then hydrolyzed ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (II) [In the formula, R' represents a lower alkyl group. represent ] A method for producing a carbamate ester derivative. (4) General formula (V) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (V) [In the formula, R is an alkyl group having 1 to 4 carbon atoms, an alkyl group that may be substituted with a halogen atom, etc.; alkenyl Group; alkynyl group; represents a cycloalkyl group. ] The general formula (I) is characterized by reacting the aniline derivative represented by the following with a carbamate agent:
There are tables, etc. ▼ (I) [In the formula, R represents an alkyl group having 1 to 4 carbon atoms, an alkyl group that may be substituted with a halogen atom, etc.; an alkenyl group; an alkynyl group; a cycloalkyl group, and R' represents a lower alkyl group. ] A method for producing a carbamate ester shown in the following. (5) General formula (VI) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (VI) [In the formula, R is an alkyl group having 1 to 4 carbon atoms, an alkyl group that may be substituted with a halogen atom, etc.; alkenyl Group; alkynyl group; represents a cycloalkyl group. ] An isocyanate derivative represented by the general formula (VII) R'-OH (VII) [wherein R' represents a lower alkyl group. ] The general formula ( I
) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) [In the formula, R is an alkyl group having 1 to 4 carbon atoms, an alkyl group that may be substituted with a halogen atom, etc.; alkenyl group; alkynyl group; cycloalkyl R' represents a lower alkyl group. ] A method for producing a carbamate ester shown in the following.