JPH0717951A - Production of urethane compound - Google Patents

Abstract

PURPOSE:To industrially advantageously produce the compound useful as an intermediate for synthesis of medicines by reacting a nitrogen-containing heterocyclic compound having an amino group with a dicarbonate in the presence of a specified tert-amine catalyst and terminating the reaction at a specified stage. CONSTITUTION:With 1mol heterocyclic compound (e.g. ethyl-2-amino-4-thiazole acetate) having an amino group and containing a nirogen atom as a heteroatom, >=1.2 mol dicarbonate (e.g di-tert-butyl dicarbonate) represented by the formula (R<1> is an alkyl, an alkenyl or an aralkyl) is reacted in the presence of a tert- amine catalyst such as an aliphatic tert-amine (e.g. N,N,N',N'- tetramethylethylenediamine) or an aromatic tert-amine (e.g. N,N- dimethylbenzylamine) in which an aromatic ring is bonded through an alkylene group to a nitrogen atom. The reaction is terminated at a stage where the amount of the objective compound is within a range of <=95% of the maximum yield to inhibit formation of by-products. Thus, the objective urethane compound can be obtained in a high yield under a mild condition.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a urethane compound, and more particularly to a method for producing a urethane compound by reacting a compound having an amino group with dicarbonate.

[0002]

BACKGROUND OF THE INVENTION Urethane compounds derived from a heterocyclic compound having an amino group and a nitrogen atom as a hetero atom are useful as intermediates in the production of pharmaceuticals, for example, antibiotics such as cephems and cephalosporins. It is an important compound used as a side chain of. Conventionally, a method for producing a urethane compound by reacting a compound having an amino group with dicarbonate is known. For example, a heterocyclic compound having an amino group and a nitrogen atom as a hetero atom, for example, 2-amino-4-thiazolemalonic acid diethyl ester and 2.25 times equivalent of dialkyl dicarbonate at 80 ° C. overnight. Method of heating (JP-A-61-161)
No. 24580) has been proposed.

[0003]

However, in the above method, since a decomposition reaction of dialkyl dicarbonate by heat occurs during the reaction, an excess amount of dialkyl dicarbonate which is more than 2-fold equivalent to the heterocyclic compound as a substrate is generated. There is the problem of having to use it.

On the other hand, it is known to react a compound having an amino group with dicarbonate in the presence of a base such as pyridine or triethylamine. However,
When the present inventors applied these bases to the reaction of a heterocyclic compound having the above amino group and containing a nitrogen atom as a hetero atom with a dicarbonate, the amino group and the dicarbonate of the heterocyclic compound were obtained. It was found that, in addition to the urethane compound reacted with, the by-product of the reaction of dicarbonate also occurred on the nitrogen atom of the heterocycle of the urethane compound, and the reaction yield of the urethane compound was extremely reduced.

In order to suppress such a by-product of the compound, it is necessary to use no base as in the above-mentioned conventional technique. However, the reaction efficiency that the reaction rate becomes extremely slow without using a base. The above problem remains. Then, in order to increase the reaction rate, it was necessary to heat it, and it was necessary to use excessive amount of dicarbonate. In the end, it was the current situation to go round without finding a solution.
In other words, there is still no known technique in which the reaction proceeds under mild conditions and does not form a compound or the like that has undergone a dicarbonate reaction with the nitrogen atom of the heterocycle as described above.

As a result of earnest studies on the development of a new technique for compensating the above-mentioned drawbacks of the prior art, the present inventors have found that a reaction between a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom, and a dicarbonate. In, an aromatic tertiary amine having an aromatic ring bound to a nitrogen atom via an aliphatic tertiary amine or an alkylene group, the reaction proceeds under mild conditions,
In addition, they have found that they effectively act as a catalyst that does not by-produce a compound in which dicarbonate is reacted with the nitrogen atom of the heterocyclic ring, and have already filed a patent application (Japanese Patent Application No. 2881889/1992).

[0007] After that, as a result of repeating the above-mentioned technique and conducting further studies, it was unexpected that, for a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom, It has been discovered that undesirable theoretical by-products are formed when carbonates are used in theoretically equivalent amounts. Surprisingly, the by-product is a compound represented by the following formula (II) in which a heterocyclic compound having two amino groups and containing a nitrogen atom as a hetero atom is bound by a urea bond.

[Chemical 2] (However, A is a heterocyclic compound containing a nitrogen atom as a hetero atom.) The production of this by-product is a heterocyclic compound in which α-hydrogen of an acetic ester has an amino group and contains a nitrogen atom as a hetero atom. A compound substituted with a compound, for example
It is particularly remarkable in 2-amino-4-thiazole acetic acid ethyl ester and the like.

[0008]

Therefore, an object of the present invention is to provide a method for producing an industrially advantageous urethane compound by reacting a compound having an amino group with a dicarbonate without producing a by-product. It is in.

[0009]

DISCLOSURE OF THE INVENTION The present invention has been proposed in order to achieve the above object, and is 1 mol of a heterocyclic compound having an amino group as described above and containing a nitrogen atom as a hetero atom. On the other hand, based on the finding obtained by the present inventors that using 1.2 mol or more of the dicarbonate represented by the general formula (I) is effective in suppressing the production of this by-product. It has been completed.

In this method, in order to prevent an increase in the by-product of the compound in which the dicarbonate has reacted with the nitrogen atom of the heterocyclic ring, that is, an excessive amount of reaction, before and after the target product reaches the maximum production amount, a constant amount is obtained. It is important to stop the reaction within the range, whereby a urethane compound can be synthesized in good yield.

That is, according to the present invention, in the presence of an aromatic tertiary amine or an aromatic tertiary amine in which an aromatic ring is bonded to a nitrogen atom via an alkylene group, a nitrogen atom having an amino group and a nitrogen atom as a hetero atom is present. The following formula (I) is used for 1 mol of the heterocyclic compound containing atoms.

[Chemical 3] (However, R ¹ is an alkyl group, an alkenyl group or an aralkyl group.)
Provided is a method for producing a urethane compound, which comprises reacting in a molar amount or more and stopping the reaction within a range where the target product is within 95% of the maximum production amount.

[0012]

DETAILED DESCRIPTION OF THE INVENTION In the present invention, it is necessary to use an aliphatic tertiary amine or an aromatic tertiary amine having an aromatic ring bonded to a nitrogen atom via an alkylene group as a catalyst.

As the above-mentioned aliphatic tertiary amine or aromatic tertiary amine in which an aromatic ring is bonded to a nitrogen atom via an alkylene group, known compounds can be adopted without any limitation. Among them, in the present invention, the following formula (III)

[Chemical 4] [Wherein R ² and R ³ are the same or different alkyl groups, R ⁴ is an alkylene group, X is a hydrogen atom, an alkoxy group, an alkylthio group, an aryl group or-{Y
(CH ₂ ) _m } _n —NR ⁵ R ⁶ {wherein R ⁵ and R ⁶ are hydrogen atoms or alkyl groups, at least one is an alkyl group, and Y is O, S or NR ⁷ (provided that R ⁷ Is a hydrogen atom or an alkyl group), m is an integer of 1 or more, and n is 0 or 1. }. ] The compound represented by the following can be particularly preferably adopted.

Specific examples of the catalyst that can be preferably used in the present invention include N, N-dimethylbenzylamine,
N, N-diethylbenzylamine, N, N, N ', N'
-Tetramethylethylenediamine, N, N, N ', N'
-Tetramethyl-1,3-propanediamine, N, N,
N ', N'-tetramethyl-1,6-hexanediamine, N, N, N', N'-tetraethylethylenediamine, N, N, N ', N'-tetraethyl-1,3-propanediamine, N, N, N ', N'-tetraethyl-
1,6-hexanediamine, N, N, N ', N'-tetramethyl-1,3-butanediamine, N, N, N',
N'-tetramethyl-1,4-butanediamine, bis-
[2- (N, N-dimethylamino) ethyl] ether,
Bis- [2- (N, N-dimethylamino) propyl] ether, bis- [2- (N, N-dimethylamino) ethyl] sulfide, bis- [2- (N, N-dimethylamino) propyl] sulfide , 2- (N, N-dimethylamino) ethyl ethyl ether, 2- (N, N-dimethylamino) ethyl ethyl sulfide, bis- [2- (N,
N-dimethylamino) ethyl] methylamine and the like can be mentioned.

Among the aliphatic tertiary amines and aromatic tertiary amines represented by the general formula (III), when a compound in which X is an aryl group or --NR ⁵ R ⁶ is used, the yield of the desired product is Since it is high, it is suitable in the present invention.

The amount of the above-mentioned aliphatic tertiary amine or aromatic tertiary amine used is not particularly limited, but in order to obtain a sufficient reaction rate, it is 0. 0001 to 0.3 times equivalent, preferably 0.0
005 to 0.2 times equivalent, more preferably 0.001
To 0.1 times the equivalent range.

The heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom in the present invention is not particularly limited in the number of amino groups and the bonding position thereof, and the number of nitrogen atoms contained in the hetero ring and The position is also not particularly limited. Further, the heterocycle may contain a hetero atom other than the nitrogen atom, for example, an oxygen atom and a sulfur atom. In the present invention, the heterocyclic compound which can be preferably used contains at least one nitrogen atom and may further contain an oxygen atom or a sulfur atom, and the number of these hetero atoms is 5 to 6 which is 1 to 3. A heterocyclic compound in which an amino group is directly bonded to a membered ring, or a condensed ring of 5- or 6-membered rings, and a condensed ring in which a benzene ring is condensed therewith. Substituents other than the amino group may be bonded to the ring of the above heterocyclic compound.

The substituent other than the amino group is not particularly limited, but an alkyl group, an alkoxy group, a hydroxyl group, a nitro group, a nitroso group, a mercapto group, a halogen atom and the like are preferable. The alkyl group is a methyl group, an ethyl group, a propyl group,
A lower alkyl group such as a butyl group is preferable, a lower alkoxy group such as a methoxy group, an ethoxy group, a propoxy group and a butoxy group is preferable as the alkoxy group, and fluorine, chlorine and bromine are preferable as the halogen atom.

The above-mentioned 5- to 6-membered ring having 1 to 3 heteroatoms, a condensed ring of 5 to 6-membered rings, or a condensed ring in which a benzene ring is condensed thereto is specifically, for example, Pyridine ring, quinoline ring, isoquinoline ring, pyrazine ring, pyrimidine ring, pyrazole ring, pyrazoline ring, imidazole ring, triazine ring, purine ring, thiazole ring, benzothiazole ring, thiadiazole ring,
Examples thereof include thiazoline ring, triazole ring, naphthyridine ring, picoline ring and the like.

Specific examples of the heterocyclic compound that can be preferably used in the present invention include 2-aminothiazole and 2-aminothiazole.
Amino-4-methylthiazole, 2-amino-4-methyl-5-thiazolesulfonyl chloride, 2-amino-5-bromothiazole, 2-amino-4- (4-chlorophenyl) thiazole, 2-amino-4,5. -Dimethylthiazole, 2-amino-5- (4-nitrophenylsulfonyl) thiazole, 2-amino-5-nitrothiazole, 2-amino-4-phenyl-5-tetrazylthiazole, 2-amino-4-phenylthiazole , 2-
Amino-4-thiazoleacetic acid, 2-amino-α- (methoxyimino) -4-thiazoleacetic acid, ethyl 2-amino-4-thiazoleacetate, ethyl 2-amino-
α- (hydroxyimino) -4-thiazole acetate, ethyl 2-amino-α- (methoxyimino) -4
A thiazole derivative such as thiazole acetate, ethyl 2-amino-4-thiazole glyoxylate, S-2-benzothiazolyl-2-amino-α- (methoxyimino) -4-thiazolethiol acetate;

2-aminobenzothiazole, 2-amino-6-ethoxybenzothiazole, 2-amino-6-fluorobenzothiazole, 2-amino-4-methoxybenzothiazole, 2-amino-4-methylbenzothiazole, 2 -Amino-6-nitrobenzothiazole, 2-
Amino-4-chlorobenzothiazole, 2-amino-
Benzothiazole derivatives such as 5,6-dimethylbenzothiazole;

5-amino-1,3,4-thiadiazole-2-sulfonamide, 2-amino-5-ethyl-1,
3,4-thiadiazole, 2-amino-6- (ethylthio) -1,3,4-thiadiazole, 2-amino-5-
Methyl-1,3,4-thiadiazole, 5-amino-3
-Phenyl-1,2,4-thiadiazole, 2-amino-1,3,4-thiadiazole, 5-amino-1,3
Thiadiazole derivatives such as 4-thiadiazole, 2-amino-5-trifluoromethyl-1,3,4-thiadiazole; thiazoline derivatives;

3-amino-5,6-dimethyl-1,2,
4-triazole, 3-amino-5-mercapto-1,
2,4-triazole, 3-amino-5-methylthio-
1H-1,2,4-triazole, 3-amino-1,
Triazole derivatives such as 2,4-triazole and 3-amino-1,2,4-triazole-5-acetic acid; triazine derivatives;

2-aminopyridine, 2-amino-3-nitropyridine, 2-amino-5-nitropyridine, 2-
Amino-4-methyl-3-nitropyridine, 2-amino-3-hydroxypyridine, 2-amino-4,6-dimethylpyridine, 2-amino-5-chloropyridine, 2-
Amino-3,5-dichloropyridine, 2-amino-3-
Chloro-5- (trifluoromethyl) pyridine, 2-amino-5-bromopyridine, 2-amino-5-bromo-
Pyridine derivatives such as 3-nitropyridine and 3-acetyl-2,6-diamino-4-methylpyridine; pyrazine derivatives;

2-aminopyrimidine, 4-aminopyrazolo [3,4-d] pyrimidine, 4-amino-6-hydroxy-2-mercapto-5-nitrosopyrimidine, 2-
Amino-4-methylpyrimidine, 2-amino-4-methoxy-6-methylpyrimidine, 4-amino-6-hydroxy-2-mercaptopyrimidine, 2-amino-4-hydroxy-6-methylpyrimidine, 4-amino- 6-hydroxypyrazolo [3,4-d] pyrimidine, 4-amino-6-mercaptopyrazolo [3,4-d] pyrimidine, 4-amino-2-mercaptopyrimidine, 2-amino-4-chloro-6 -Methylpyrimidine, 2-amino-
6-chloro-2- (methylthio) pyrimidine, 2-amino-4,6-dichloropyrimidine, 6-amino-2,4
-Dihydroxy-5-nitrosopyrimidine, 2-amino-4,6-dihydroxypyrimidine, 2-amino-4,
Pyrimidine derivatives such as 6-dimethoxypyrimidine, 2-amino-4,6-dimethylpyrimidine and 2-amino-5-bromopyrimidine;

3-aminopyrazole, 5-amino-1-
Ethylpyrazole, 3-amino-5-hydroxypyrazole, 3-amino-5-methylpyrazole, ethyl 3-
Pyrazole derivatives such as amino-4-pyrazole carboxylate, 3-amino-4-pyrazole carbonitrile, 3-amino-4-pyrazole carboxamide, 3-amino-4-pyrazole acetic acid; pyrazoline derivatives;

2-aminopurine, 6-aminopurine, 2
-Amino-6-chloropurine, 2-amino-6,8-dihydroxypurine, 2-amino-6-hydroxy-8-
Purine derivatives such as mercaptopurine and 2-aminopurinethiol;

2-aminoimidazole, 2-amino-
Examples include imidazole derivatives such as 4,5-imidazole dicarbonitrile, 2-aminobenzimidazole and 2-amino-5,6-dimethylbenzimidazole; naphthyridine derivatives; isoquinoline derivatives; nicotine derivatives; picoline derivatives.

On the other hand, the dicarbonate used in the present invention is a compound represented by the above general formula (I).
In the formula, the alkyl group represented by R ¹ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group,
A lower alkyl group such as i-butyl group and t-butyl group is preferable, an alkenyl group is preferably an allyl group, and an aralkyl group is preferably a benzyl group.

Specific examples of the dicarbonate represented by the general formula (I) include di-t-butyl dicarbonate,
Examples thereof include dimethyl dicarbonate, diethyl dicarbonate, di-i-propyl dicarbonate, diallyl dicarbonate, dibenzyl dicarbonate and the like.

In the present invention, it is not preferable to use the dicarbonate in an equivalent amount with respect to the heterocyclic compound having an amino group and a nitrogen atom as a hetero atom because the above-mentioned by-product having a urea bond is produced. In order to obtain the desired product in good yield, the amount of dicarbonate to be used should be 1.2 mol or more per 1 mol of the heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom. . Since it is not economically advantageous to use it in an excessive amount, it is necessary to add 2 to 1 mole of the above heterocyclic compound.
It is preferably in the range up to moles, and more preferably up to 1.7 moles.

The reaction in the present invention easily proceeds in an organic solvent or without solvent. The solvent that can be used is not particularly limited, and aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane and heptane; nitriles such as acetonitrile; ethers such as 1,4-dioxane and tetrahydrofuran. ;acetone,
Ketones such as methyl ethyl ketone; amides such as N, N-dimethylformamide and N-methylpyrrolidone; 2-
Alcohols such as propanol and 2-methyl-2-propanol; halogenated hydrocarbons such as chloroform, dichloromethane and 1,2-dichloroethane; and carbonates such as dimethyl carbonate and diethyl carbonate can be used. These organic solvents may be used alone, or may be used as a mixed solvent of two or more kinds at all.

In particular, when the reaction is carried out with an aliphatic hydrocarbon such as hexane or heptane among the above-mentioned solvents, the production of a compound in which two heterocyclic compounds which are by-products are bound by a urea bond is suppressed, It can be preferably used. The concentration of the heterocyclic compound as a raw material in the organic solvent varies depending on the type of substrate, the type of organic solvent, the composition of the mixed solvent and the stirring effect, but it is generally selected from the range of 0.5 to 60% by weight. preferable.

The reaction temperature in this reaction is not particularly limited, but if the temperature is too low, the reaction rate becomes small, and if the temperature is too high, the product decomposes. Therefore, it is usually -20 to 80.
C., preferably 0 to 50.degree. C. The reaction can be carried out under any of normal pressure, increased pressure and reduced pressure, and the time required for the reaction varies depending on the reaction temperature and the kind of the solvent, but usually the reaction for 0.1 to 30 hours is sufficient.

The reaction of the heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom with the dicarbonate carried out under the above conditions is carried out via the aliphatic tertiary amine or alkylene group as a catalyst as described above. By using an aromatic tertiary amine having an aromatic ring bonded to a nitrogen atom, the starting heterocyclic compound is converted to the target urethane compound and completely disappears, and then the heterocyclic compound of the urethane compound is further removed. The dicarbonate reacts with the nitrogen atom etc. to produce a by-product, which proceeds through a precise sequential reaction. The most technical feature of the present invention is to pay attention to the fact that this by-product is formed through sequential reactions, and this reaction is formed by the reaction between the amino group of the target heterocyclic compound and dicarbonate. This is because the reaction was stopped in the range where the urethane compound was within 95% of the maximum production amount, and the mixture of by-products into the target urethane compound was suppressed as much as possible.
In the reaction of a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom with a dicarbonate, it is the first time that the present inventors have found a catalyst capable of such a precise sequential reaction. As in the present invention, the concept of stopping the reaction after the target product reaches the maximum production amount does not come out without the use of this catalyst.

In the present invention, when the above reaction is stopped, the amount of the urethane compound produced by the reaction between the amino group of the target heterocyclic compound and dicarbonate is 95% of the maximum amount as described above. When it is within.
When to stop such reactions, preliminary experiments
It is preferable to measure the change over time in the amount of the urethane compound produced in the reaction of the dicarbonate with a heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom, and obtain it in advance.

In the present invention, the method for stopping the reaction is
There is no particular limitation, but the following method can be particularly preferably adopted. For example, the reaction can be stopped by adding water. In this case, the water may be acidic, neutral or alkaline, but considering the stability of the urethane compound as a product, it is preferably in the range of pH 1 to 14, more preferably pH 2 to 12, and even more preferably pH 3. It is preferably in the range of 10 to 10. The amount of water to be added may be equal to or more than the excess amount of dicarbonate.

By heating, the remaining dicarbonate can be decomposed and the reaction can be stopped.
The heating temperature is not particularly limited, but it is preferable to perform heating near the boiling point of the solvent used in order to quickly stop the reaction. Conversely, the reaction can be stopped by cooling. The cooling temperature is not particularly limited, but in order to quickly stop the reaction, it is preferable to cool to 10 ° C. or lower, and further to 0 ° C. or lower.

The reaction can be stopped by adding alcohol and removing the remaining dicarbonate. This utilizes the fact that dicarbonate rapidly reacts with alcohol, and is nothing but the production of a carbonate compound. In the presence of a catalyst, the reaction of dicarbonate and alcohol becomes even faster,
Since the dicarbonate reacts with the alcohol in preference to the reaction with the heterocyclic compound, excess dicarbonate is removed as a result, and the reaction is stopped. The type of alcohol used is not particularly limited, but primary or secondary alcohols are preferred for promptly stopping the reaction.

Specific examples of the above primary or secondary alcohols include, for example, methanol, ethanol, n-
Propanol, i-propanol, n-butanol, n
-Pentanol, cyclopentanol, n-hexanol, cyclohexanol, ethylene glycol, diethylene glycol, 1,2-propanediol, 1,6-
Hexanediol and the like can be mentioned. The amount of alcohol to be added is not limited as long as it is added in an amount equal to or more than the excess amount of dicarbonate. Thus, a urethane compound having a urethane bond formed by the reaction of an amino group of a heterocyclic compound and dicarbonate is used as a by-product of a by-product such as a compound in which the nitrogen atom of the heterocycle is also reacted with dicarbonate in the urethane compound. Can be obtained by suppressing.

[0041]

According to the present invention, the production of by-products is suppressed,
It is possible to provide a method for obtaining a urethane compound in a high yield under mild conditions.

[0042]

The present invention will be described below with reference to examples and comparative examples, but the present invention is not limited to these examples.

Example 1 In a 200 ml eggplant type flask, ethyl 2-amino-4-thiazole acetate 1 was added.
8.6 g (0.1 mol), di-t-butyl dicarbonate 32.7 g (0.15 mol), N, N, N ',
N'-tetramethylethylenediamine 0.58 g (5 m
mol) and 65 ml of hexane were added, and the mixture was stirred at 25 ° C.

The reaction solution was sampled every 10 minutes from the start of the reaction and subjected to high performance liquid chromatography (hereinafter referred to as HPL).
The reaction product was traced by C), and after 2 hours from the start of the reaction, the target product ethyl 2-
(T-Butoxycarbonylamino) -4-thiazoleacetate reached its maximum production amount, and the amount of the intended product at this time was 24.8 g (yield 86.7%). After that, stirring was continued and the reaction composition was traced by HPLC in the same manner, and the results are shown in Table 1. Moreover, the state is shown in FIG. The target compound after 24 hours had decreased to 11.3 g, at which time the by-product having two t-butoxycarbonyl groups had increased to 19.4 g.

[0045]

Based on the above results, the same operation is performed,
Two hours after the start of the reaction, which is the time to reach the maximum production amount of the target substance, 30 ml of ion-exchanged water having a pH of 6 was added to the reaction solution.
After that, continue stirring, and after adding ion-exchanged water,
After a lapse of time, a part of the reaction solution was sampled and quantified by HPLC. As a result, the desired product was 24.8 g (yield 86.
7%). In addition, t-butoxycarbonyl group 2
None of the by-products having the same or by-products having a urea bond were detected.

<Comparative Example 1> After the reaction was carried out in the same manner as in Example 1, 4 hours after the reaction was started, ion-exchanged water 3 of pH 6 was added.
0 ml was added. The target product after the addition was 21.0 g (yield 73.4%, maximum production amount 84.7%). At this time, the amount of the by-product having two t-botoxycarbonyl groups was increased to 7.2 g, and the purity of the target product in the reaction solution was significantly reduced.

<Examples 2 to 6> Using the heterocyclic compounds shown in Table 2 and using 1.5 times mol of di-t-butyl dicarbonate with respect to the heterocyclic compound, the same procedure as in Example 1 was conducted. Table 2 shows the results of conducting a preliminary experiment to determine the time for the target product to reach the maximum production amount, and then performing the same reaction and the reaction termination operation at the time of maximum production of the target product based on the results. .

[0049]

<Examples 7 to 11> Preliminary experiments were carried out in the same manner as in Example 1 using the catalysts shown in Table 3 to determine the time required for the target product to reach the maximum production amount. Based on the results, Table 3 shows the results of the similar reaction and the operation of stopping the reaction at the maximum production of the target substance.

[0051]

<Examples 12 to 14> A dicarbonate shown in Table 4 was used in a 1.5-fold molar amount with respect to the heterocyclic compound, and a preliminary experiment was conducted in the same manner as in Example 1 to find that the target product had the maximum production amount. Table 4 shows the results of performing the same reaction and the reaction termination operation at the maximum production of the target compound based on the result after the time required to reach was reached.

[0053]

[Brief description of drawings]

FIG. 1 is a diagram showing a change with time in the amount of a urethane compound, which is a reaction product, produced during a reaction in Example 1 of the present invention.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical display location C07D 277/82 285/135 473/02

Claims (1)

[Claims] 1. A heterocyclic compound having an amino group and containing a nitrogen atom as a hetero atom in the presence of an aliphatic tertiary amine or an aromatic tertiary amine having an aromatic ring bound to a nitrogen atom via an alkylene group. With respect to 1 mol, the following formula (I): (However, R ¹ is an alkyl group, an alkenyl group, or an aralkyl group.)
95% of the maximum amount of the product is produced by reacting more than 2 mol
A method for producing a urethane compound, characterized in that the reaction is stopped within a certain range.