JP2000007624A - Production of optically active 2-amino-substituted tetralin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially advantageously produce the subject compound useful as an intermediate or the like for a compound which is a β2- and β3-adrenaline, without using an expensive raw material by cyclizing a specific optically active hydroxyaminotetralin compound, and subjecting the cyclized product to hydrocracking. SOLUTION: An optically active hydroxyaminotetralin compound of formula I [R1 is H, OH or the like; R2 is a (substituted) 1-20C leaving group; (*) represent an asymmetric carbon], [e.g. 2S-1-hydroxy-2-(methoxycarbonyl)amino-7- methoxytetralin] is cyclized to provide an optically active oxazolidinone derivative of formula II preferably a compound of formula III [(S) represents S- configuration], and hydrocracking the obtained oxazolidinone derivative preferably in the presence of a palladium-carbon as a catalyst preferably by using perchloric acid or the like in a carboxylic acid preferably at 50-90 deg.C to provide the objective compound of formula IV (preferably the compound of formula V).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing an optically active 2-amino-substituted tetralin. More specifically, for example, the present invention relates to a method for producing an optically active 2-amino-substituted tetralin which is useful as an intermediate of phenylethanolaminotetralins which are β ₂ and β ₃ -adrenoreceptor agonists.

[0002]

2. Description of the Related Art Conventionally, 2-amino-substituted tetralin has been prepared by (A) using a 2-carboxyethyl-1-tetralol derivative as a starting material and hydrolyzing the 2-carboxyethyl-1-tetralol derivative. And hydrogenation to give 1,2,3,4-tetrahydronaphthalenecarboxylic acid, which is then aminated with oxalyl chloride and sodium azide in diethyl ether,
(B) using a 2-carboxyethyl-1-tetralol derivative as a starting material,
A method has been proposed in which a tetralol derivative is converted into an oxazolidinone derivative using diphenylphosphoryl azide and then catalytically reduced [Tetrahedron Letters, Vol. 35, No. 19,
3091-3094 (1994)].

[0003] However, the starting materials used in the above methods (A) and (B), which are carboxyethyl-1-tetralol derivatives, are expensive as raw materials. Since a complicated operation is required, development of a method for industrially and advantageously producing a 2-amino-substituted tetralin without using the carboxyethyl-1-tetralol derivative has been desired.

Further, in the method (B), the catalytic reduction of the oxazolidinone derivative is carried out in ethanol in the presence of palladium carbon using hydrogen chloride. Is
Mild reaction conditions for suppressing the overreduction of the benzene ring, which is a side reaction, are required. However, under these reaction conditions, the reactivity is very low, and the yield of the target product, 2-amino-substituted tetralin, is extremely low. There is a disadvantage that.

[0005]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above-mentioned prior art, and an optically active 2-amino-substituted tetralin is industrially produced without using an expensive carboxyethyl-1-tetralol derivative. It is an object of the present invention to provide a method that can be advantageously manufactured.

[0006]

That is, the gist of the present invention is as follows.
[1] (A) General formula (I):

[0007]

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Wherein R ¹ is a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxy group or a halogen atom having 1 to 3 carbon atoms, and R ² is a carbon atom which may have a substituent. 1 to 20 leaving groups, * represents an asymmetric carbon atom), and the optically active hydroxyaminotetralin compound represented by the formula (B) is subjected to ring closure to obtain the general formula (II):

[0009]

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Wherein R ¹ and * are the same as defined above, wherein the optically active oxazolidinone derivative represented by the general formula (III) is hydrogenolyzed.

[0011]

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Wherein R ¹ and * are the same as defined above, and a method for producing an optically active 2-amino-substituted tetralin;
[2] The method according to the above [1], wherein the optically active oxazolidinone derivative is hydrogenolyzed in the presence of palladium carbon as a catalyst, [3] The optically active oxazolidinone derivative is hydrogenolyzed using perchloric acid or methanesulfonic acid. The production method according to the above [1] or [2],
[4] The method according to any one of the above [1] to [3], wherein the optically active oxazolidinone derivative is hydrogenolyzed in a carboxylic acid; [5] The above [1] to [1] wherein the carboxylic acid is acetic acid
[4] The production method according to any of [6], wherein the optically active hydroxyaminotetralin compound represented by the general formula (I) is
General formula (Ia):

[0013]

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(Wherein (S) represents the S-configuration and R ² is the same as described above), and is an optically active oxazolidinone derivative represented by the general formula (II) Has the general formula (II-a):

[0015]

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(Wherein (S) is the same as described above) and is an optically active oxazolidinone derivative represented by the general formula (III)
The optically active 2-amino-substituted tetralin represented by the formula (I)
II-a):

[0017]

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The process according to any one of the above [1] to [5], which is an optically active 2-amino-substituted tetralin represented by the formula:
[7] In the optically active hydroxyaminotetralin compound represented by the general formula (Ia), R ² is a methyl group, n-
A process according to the above [6], which is a propyl group or a phenyl group, [8] (B) a general formula (II):

[0019]

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Wherein the optically active oxazolidinone derivative represented by the formula ( ¹ ) is hydrogenolyzed in a carboxylic acid using perchloric acid or methanesulfonic acid. (III):

[0021]

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Wherein R ¹ and * are the same as defined above, and a method for producing an optically active 2-amino-substituted tetralin;

[9] The method according to [8], wherein the optically active oxazolidinone derivative is hydrogenolyzed in the presence of palladium carbon as a catalyst, [10] wherein the carboxylic acid is acetic acid;

[9] The production method described in [9], wherein the optically active hydroxyaminotetralin compound represented by the general formula (I) is represented by the general formula (Ia):

[0023]

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(Wherein (S) represents the S-configuration, and R ² is the same as described above), and is an optically active oxazolidinone derivative represented by the general formula (II) Has the general formula (II-a):

[0025]

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(Wherein (S) is the same as the above) and is an optically active oxazolidinone derivative represented by the following general formula (III):
The optically active 2-amino-substituted tetralin represented by the formula (I)
II-a):

[0027]

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The process according to any one of the above [8] to [10], which is an optically active 2-amino-substituted tetralin represented by the formula:
[12] In the optically active hydroxyaminotetralin compound represented by the general formula (Ia), R ² is a methyl group, n
A propyl group or a phenyl group;

[0029]

DETAILED DESCRIPTION OF THE INVENTION According to the production method of the present invention, general formula (I):

[0030]

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(Wherein, R ¹ represents a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms or a halogen atom, and R ² represents a carbon atom which may have a substituent. 1 to 20 leaving groups, * indicates an asymmetric carbon atom), and the optically active hydroxyaminotetralin compound represented by the general formula (II):

[0032]

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The optically active oxazolidinone derivative represented by the formula (wherein R ¹ and * are as defined above) is hydrogenated to give an optically active 2-amino-substituted tetralin.

The optically active hydroxyaminotetralin compound represented by the general formula (I) is an inexpensive L-hydroxyaminotetralin compound.
It is an inexpensive compound that can be easily prepared by using aspartic acid as a starting material. The optically active hydroxyaminotetralin compound can be prepared by a known method, for example,
It can be obtained by the method described in JP-A-63-5087.

In the general formula (I), R ¹ represents a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms,
Is an alkoxy group or a halogen atom. Carbon number 1
Examples of the alkyl group 3 include a methyl group, an ethyl group, an n-propyl group and an isopropyl group. Carbon number 1
Examples of the alkoxy groups (1) to (3) include a methoxy group, an ethoxy group, an n-propoxy group and an isopropoxy group. Examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom. Of these, a methoxy group is preferred.

R ² represents a leaving group having 1 to 20 carbon atoms which may have a substituent. Specific examples of the leaving group having 1 to 20 carbon atoms include, for example, an alkyl group such as a methyl group, an ethyl group, a propyl group, and an isopropyl group, an aralkyl group such as a benzyl group and a phenylethyl group, a phenyl group, a naphthyl group, And an aryl group such as a substituted phenyl group. Among these, a methyl group, an n-propyl group, and a phenyl group are preferable from the viewpoint that the raw material is inexpensive and the operability during production is good.

* Is an asymmetric carbon atom as described above.

Among the optically active hydroxyaminotetralin compounds represented by the general formula (I), those which can be suitably used include those represented by the general formula (Ia):

[0039]

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(Wherein (S) represents the S-configuration, and R ² is the same as described above). In the general formula (Ia), R ² is more preferably a methyl group, an n-propyl group or a phenyl group.

In the present invention, the optically active hydroxyaminotetralin compound represented by the general formula (I) is first closed. Ring closure of the optically active hydroxyaminotetralin compound can be performed using an alkali metal hydride.

As the alkali metal hydride, for example,
Examples include sodium hydride, potassium hydride, lithium hydride and the like. Since these alkali metal hydrides are generally easily available and inexpensive compounds, the optically active 2-amino-substituted tetralin, which is the target compound of the present invention, can be industrially advantageously produced.

The amount of the alkali metal hydride used is based on 1 mol of the optically active hydroxyaminotetralin compound.
It is preferably at least 1 mol, preferably at least 1.4 mol, and from the viewpoint of economy, it is desirably at most 3 mol, preferably at most 2 mol.

In the reaction, a solvent can be used. Examples of such a solvent include ethers such as tetrahydrofuran and diethyl ether; aromatic hydrocarbons such as toluene, xylene and chlorobenzene; and polar solvents such as dimethylformamide (DMF). The amount of the solvent used is usually 200 to 100 parts by weight of the optically active hydroxyaminotetralin compound.
It may be about 4000 parts by weight.

After dissolving the optically active hydroxyaminotetralin compound in a solvent, the reaction can be carried out by adding an alkali metal hydride to the solution, and the reaction atmosphere is, for example, nitrogen gas. It is preferable that the gas is replaced by an inert gas such as argon gas.

The reaction temperature is selected from the viewpoint of accelerating the reaction.
The temperature is desirably 0 ° C or higher, preferably 40 ° C or higher, and is desirably 150 ° C or lower, preferably 100 ° C or lower from the viewpoint of energy saving.

During the reaction, it is preferable to stir the reaction solution in order to accelerate the reaction.

The completion of ring closure of the optically active hydroxyaminotetralin compound can be confirmed by examining the content of the optically active hydroxyaminotetralin compound by high performance liquid chromatography (hereinafter, referred to as HPLC) analysis.

After completion of the reaction, the resulting optically active hydroxyaminotetralin compound is subjected to ring closure to separate the optically active oxazolidinone derivative represented by the general formula (II) from other components. Preferably, an aqueous solvent such as methylene chloride and an organic solvent such as methylene chloride are added.

An aqueous solvent and an organic solvent are added,
After sufficiently stirring at a temperature of about 80 ° C., the mixture is allowed to stand still at that temperature, separated and separated into an aqueous layer and an organic solvent layer, and then the organic solvent layer is separated.

A desiccant such as magnesium sulfate is added to the separated organic solvent layer, the desiccant is removed, and the organic layer is concentrated and cooled to obtain a generated optically active oxazolidinone derivative. Can be.

Among the optically active oxazolidinone derivatives represented by the general formula (II) thus obtained, the general formula (II-
a):

[0053]

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The optically active oxazolidinone derivative represented by the formula (wherein (S) is as defined above) can be suitably used.

Next, the optically active oxazolidinone derivative is hydrogenolyzed to obtain the compound of the formula (III):

[0056]

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(Wherein R ¹ and * are as defined above) to obtain an optically active 2-amino-substituted tetralin.

As a method for producing an optically active 2-amino-substituted tetralin by hydrogenolysis of an optically active oxazolidinone derivative, for example, the optically active oxazolidinone derivative is converted into a carboxylic acid using perchloric acid or methanesulfonic acid. Examples of the method include a hydrocracking reaction.

In general, an optically active oxazolidinone derivative has an R ¹ group. When an electron-donating R ¹ group is present, the benzene ring to which the R ¹ group is bonded has an excess. May be reduced. However, when perchloric acid or methanesulfonic acid is present in the hydrogenolysis of the optically active oxazolidinone derivative, unexpectedly, the reaction is promoted, and the overreduction is prevented, resulting in a high yield. Thus, an excellent effect that an optically active 2-amino-substituted tetralin as a target compound can be obtained is exhibited.

Therefore, in the present invention, when hydrogenating and decomposing the optically active oxazolidinone derivative, it is preferable to use perchloric acid or methanesulfonic acid.

The amount of perchloric acid or methanesulfonic acid used is based on 1 mol of the optically active oxazolidinone derivative.
From the viewpoint of increasing the reaction rate, the amount is desirably 0.1 mol or more, preferably 0.2 mol or more, and from the viewpoint of economy, it is desirably 4 mol or less, preferably 2 mol or less.

As the carboxylic acid, for example, acetic acid,
2-8 carbon atoms such as propionic acid, valeric acid and chloroacetic acid
And the like. Among them, acetic acid is particularly preferred from the viewpoint of economy, operability and yield.

From the viewpoint of reactivity and operability, the amount of the carboxylic acid used is determined based on the amount of the optically active oxazolidinone derivative 100.
500 parts by weight or more, preferably 1000 parts by weight
It is preferable that the amount is not less than parts by weight, and from the viewpoint of economy,
It is desirable that the content be 5000 parts by weight or less, preferably 3000 parts by weight or less.

At the time of the reaction, a catalyst is used. Examples of the catalyst include palladium hydroxide carbon and palladium carbon. From the viewpoint of shortening the reaction time, the amount of the catalyst to be used is 0.00 in terms of metal weight based on 100 parts by weight of the optically active oxazolidinone derivative.
It is preferably 1 to 40 parts by weight, especially 0.1 to 20 parts by weight.

An optically active oxazolidinone derivative is dissolved in a carboxylic acid, and perchloric acid or methanesulfonic acid is added thereto, followed by hydrogenolysis. Such hydrogenolysis is usually carried out in a reaction vessel. It can be performed by heating in a gas atmosphere.

The atmosphere of hydrogen gas can be adjusted, for example, by replacing the atmosphere inside the reaction vessel with hydrogen gas. The pressure of the hydrogen gas atmosphere does not need to be particularly high, and is preferably from normal pressure to 10 atm, and more preferably from normal pressure to 3 atm.

The temperature in the reaction vessel is determined from the viewpoint of economy.
The temperature is desirably 30 ° C. or higher, preferably 50 ° C. or higher. From the viewpoint of preventing a sequential reaction, the temperature is desirably 110 ° C. or lower, preferably 90 ° C. or lower.

When hydrogenating the optically active oxazolidinone derivative, the reaction solution is preferably stirred.

The completion of the hydrogenolysis of the optically active oxazolidinone derivative can be confirmed by checking the content of the optically active oxazolidinone derivative and the content of the optically active 2-amino-substituted tetralin compound in the reaction solution by HPLC. .

After the completion of the reaction, the catalyst was filtered off from the mixed solution.
Collect the filtrate.

Next, the recovered filtrate is preferably concentrated under reduced pressure in order to remove the carboxylic acid. The filtrate concentrated under reduced pressure contains optically active 2-amino-substituted tetralin, but when perchloric acid or methanesulfonic acid is used, the perchlorate or methanesulfonate of optically active 2-amino-substituted tetralin is used. It is included.

An organic solvent such as toluene and a basic aqueous solution such as sodium hydroxide are added to the filtrate concentrated under reduced pressure.
The optically active 2-amino-substituted tetralin can be obtained by extracting the optically active 2-amino-substituted tetralin into the organic solvent layer and concentrating the organic solvent layer. At this time, the amount of the base contained in the basic aqueous solution is desirably equal to or more than the equivalent of perchloric acid or methanesulfonic acid used, and preferably a large excess. Also, the pH of the aqueous solution at the time of extraction is
It is preferably highly basic.

Among the thus obtained optically active aminotetralins represented by the general formula (III), the following formula (III-a):

[0074]

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The optically active 2-amino-substituted tetralin represented by the following formula can be suitably used.

Optical activity 2 obtained by the production method of the present invention
-The optical purity of the amino-substituted tetralin, when measured using HPLC, cannot be unequivocally defined because it differs depending on the type of the substituent, but is usually from 95 to 99.9.
% Ee.

The yield of the optically active 2-amino-substituted tetralin with respect to the optically active hydroxyaminotetralin compound is about 40 to 95%.

As described above, according to the present invention, an optically active 2-amino-substituted tetralin is prepared by using an inexpensive optically active hydroxyaminotetralin compound which can be easily prepared from L-aspartic acid which can be obtained at low cost. Can be obtained efficiently and with high purity and high yield, and thus the production method of the present invention is a method with excellent industrial productivity.

As described above, the obtained optically active 2-amino-substituted tetralin is, for example, β ₂ and β ₃
-It can be suitably used as an intermediate of phenylethanolaminotetralin, which is an adrenergic receptor agonist.

[0080]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to only these examples.

Example 1 [Production of optically active oxazolidinone derivative] A 500 equipped with a thermometer, a stirrer and a condenser was prepared.
In a four-necked flask having a capacity of 2 ml, 2S-1-
Hydroxy-2- (methoxycarbonyl) amino-7-
20 g (79.60 mmol) of methoxytetralin, 6
4.8 g (12%) of 0% sodium hydride wet paraffin
0.83 mmol) and 200 m of tetrahydrofuran
and heated to the reflux temperature (66 ° C.). After stirring at the same temperature for 6 hours while tracking the reaction by HPLC,
100 ml of water and 200 ml of methylene chloride were introduced into the flask. After that, the liquid temperature in the flask is adjusted to 40 to 50
The mixture was adjusted to ° C. and stirred for 0.5 hour. The mixture was allowed to stand still at the same temperature, and liquid-separated to separate an organic layer.

The obtained organic layer was dried over magnesium sulfate, and then this magnesium sulfate was separated by filtration. The obtained filtrate was concentrated to precipitate crude crystals, and then 50 ml of ethyl acetate was added thereto.

Next, the solution temperature of the obtained solution was set to 50 to 60 ° C.
And stirred for about 0.5 hour. Thereafter, the solution was cooled to 0 to 10 ° C., aged for 1 hour while maintaining the same temperature, and filtered to take out crystals.

The obtained crystals were dried and (3aS) -3
a, 4,5,9b-Tetrahydro-8-methoxynaphtho [2,1-d] oxazol-2 (3H) one 11.2
g was obtained (yield 64.0%).

(3aS) -3a, 4,5,9b obtained
The physical properties of -tetrahydro-8-methoxynaphtho [2,1-d] oxazol-2 (3H) one are shown below. (1) Melting point: 188.4 ° C. (2) IR (KBr): 3320, 2948, 175
8, 1730, 1492, 1216, 1040, 93
4,776 cm ^-1 (3) ¹ H-NMR (270.05 MHz, DMSO-
_{d 6) δ: 1.81-2.27 (m} , 2H), 2.88
-3.06 (m, 2H), 3.50-3.60 (m, 1
H), 3.83 (s, 3H), 5.09 (d, J = 1
1.2 Hz, 1 H), 6.84-7.19 (m, 3
H), 8.00 (s, 1H) ¹³ C-NMR (67.8 MHz, DMSO-d ₆ ) δ:
24.01, 25.18, 55.12, 57.29, 8
0.18, 106.94, 113.43, 125.6
6, 130.01, 135.65, 157.38, 15
9.91

Example 2 [Production of optically active 2-amino-substituted tetralin] 100 equipped with a thermometer, a stirrer and a condenser
(3aS) in a four-neck flask having a capacity of 500 ml under a nitrogen atmosphere.
-3a, 4,5,9b-Tetrahydro-8-methoxynaphtho [2,1-d] oxazol-2 (3H) one
0 g (4.56 mmol), 0.77 g of 60% perchloric acid
(4.60 mmol) and 5% palladium on carbon (containing 2% sodium, water content 50% by weight) 0.1
g and 20 ml of acetic acid at normal pressure and a reaction temperature of 55
Hydrogen gas was introduced at ~ 65 ° C and stirred vigorously for 11 hours while monitoring the reaction by HPLC.

The end point of the reaction was determined by HPLC using (3aS) -3a, 4,5,9b-tetrahydro-
8-methoxynaphtho [2,1-d] oxazole-2
It was confirmed by measuring the (3H) on content.

After completion of the reaction, the catalyst was filtered from the reaction solution,
The mixture was concentrated under reduced pressure using an evaporator to obtain a perchlorate of optically active 2-amino-7-methoxytetralin.

The obtained perchlorate of optically active 2-amino-7-methoxytetralin was liberated with 100 ml of a 4% aqueous solution of sodium hydroxide, extracted with toluene and concentrated to give a (99% ee optical purity) 0.60 g of a free form of S)-(−)-2-amino-7-methoxytetralin was obtained as an oil. (S)-(−)-2-amino- obtained
(3aS) -3a, 4,5 of 7-methoxytetralin
9b-tetrahydro-8-methoxynaphtho [2,1-
d] Oxazol-2 (3H) one yield is 7
It was 4.1%.

Example 3 In Example 2, 0.77 g (4.6%) of 60% perchloric acid was used.
0 mmol) instead of 0.44 g of methanesulfonic acid
(4.66 mmol) except that 0.33 g of a free form of (S)-(-)-2-amino-7-methoxytetralin having an optical purity of 99% ee was obtained in the same manner as in Example 2 except that oil was used. As obtained. (S)-(−)-2-amino-7 obtained
(3aS) -3a, 4,5,9 of -methoxytetralin
b-tetrahydro-8-methoxynaphtho [2,1-d]
The yield based on oxazol-2 (3H) one was 40.2.
%Met.

Comparative Example 1 100 equipped with a thermometer, a stirrer and a condenser
After replacing the inside of the four-neck flask with
% Palladium carbon (water content 50% by weight) 0.1
g, 4.8% hydrochloric acid-ethanol solution (20 ml) and (3
aS) -3a, 4,5,9b-Tetrahydro-8-methoxynaphtho [2,1-d] oxazol-2 (3H) one (1.0 g, 4.60 mmol) was charged and the temperature was raised to 60 ° C.

Next, after the inside of the flask was replaced with hydrogen gas,
Stir for 11 hours while tracking the reaction by HPLC at normal pressure,
The reaction was performed.

The catalyst was filtered from the obtained reaction solution, and the filtrate was analyzed by HPLC. As a result, the obtained (S)-(-) was obtained.
(3aS)-of -2-amino-7-methoxytetralin
The yield based on 3a, 4,5,9b-tetrahydro-8-methoxynaphtho [2,1-d] oxazol-2 (3H) one was 2.7%. The raw material (3aS)-
3a, 4,5,9b-Tetrahydro-8-methoxynaphtho [2,1-d] oxazol-2 (3H) one can be prepared by using the starting material [(3aS) -3a, 4,5,9b-tetrahydro-8-methoxy] 64.8% remained with respect to naphtho [2,1-d] oxazol-2 (3H) one].

From the above results, according to the production method of the present invention,
It is understood that the optically active 2-amino-substituted tetralin can be industrially advantageously produced with high optical purity and high yield.

[0095]

According to the process of the present invention, an excellent effect that an optically active 2-amino-substituted tetralin can be industrially advantageously produced without using an expensive carboxyethyl-1-tetralol derivative. Is played.

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Claims (12)

[Claims] (A) General formula (I): (Wherein, R ¹ represents a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms or a halogen atom, and R ² has 1 to 20 carbon atoms which may have a substituent. (* Indicates an asymmetric carbon atom), and the optically active hydroxyaminotetralin compound represented by the formula (B)
The obtained general formula (II): Wherein R ¹ and * are the same as described above, wherein the optically active oxazolidinone derivative represented by the general formula (III) is hydrogenolyzed. (Wherein, R ¹ and * are the same as described above). 2. The process according to claim 1, wherein the optically active oxazolidinone derivative is hydrogenolyzed in the presence of palladium carbon as a catalyst. 3. The process according to claim 1, wherein the optically active oxazolidinone derivative is hydrogenolyzed using perchloric acid or methanesulfonic acid. 4. The process according to claim 1, wherein the optically active oxazolidinone derivative is hydrogenolyzed in a carboxylic acid. 5. The method according to claim 1, wherein the carboxylic acid is acetic acid. 6. An optically active hydroxyaminotetralin compound represented by the general formula (I) is represented by the general formula (Ia): (Wherein (S) represents the S-configuration, and R ² is the same as described above)
Wherein the optically active oxazolidinone derivative represented by the general formula (II) is represented by the general formula (II-a): (Wherein (S) is the same as described above) and is an optically active oxazolidinone derivative represented by the general formula (III), wherein the optically active 2-amino-substituted tetralin is represented by the formula (III-a): 6] The method according to claim 1, which is an optically active 2-amino-substituted tetralin represented by the formula: 7. The method according to claim 6, wherein in the optically active hydroxyaminotetralin compound represented by the formula (Ia), R ² is a methyl group, an n-propyl group or a phenyl group. (B) General formula (II): (Wherein, R ¹ represents a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxy group having 1 to 3 carbon atoms or a halogen atom, and * represents an asymmetric carbon atom). Is hydrogenolyzed in a carboxylic acid using perchloric acid or methanesulfonic acid, characterized by the general formula (III): (Wherein, R ¹ and * are the same as described above). 9. The method according to claim 8, wherein the optically active oxazolidinone derivative is hydrogenolyzed in the presence of palladium carbon as a catalyst. 10. The method according to claim 8, wherein the carboxylic acid is acetic acid. 11. An optically active hydroxyaminotetralin compound represented by the general formula (I) is represented by the general formula (Ia): (Wherein (S) represents the S-configuration, and R ² is the same as described above)
Wherein the optically active oxazolidinone derivative represented by the general formula (II) is represented by the general formula (II-a): (Wherein (S) is the same as described above) and is an optically active oxazolidinone derivative represented by the general formula (III), wherein the optically active 2-amino-substituted tetralin is represented by the formula (III-a): 11] The method according to any one of claims 8 to 10, which is an optically active 2-amino-substituted tetralin represented by the formula: 12. The optically active hydroxyaminotetralin compound represented by the formula (Ia), wherein R ² is a methyl group, an n-propyl group or a phenyl group.
The manufacturing method described.