JP2001139564A - Method of producing optically active oxazolidinone compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of producing an optically active oxazolidinone compound useful as an intermediate for producing a β-blocker, by using an optically active tris-(2,3-epoxyalkyl)-isocyanurate compound as a starting material. SOLUTION: This method of producing the optically active oxazolidinone compound comprises reacting the optically active tris-(2,3-epoxyalkyl)- isocyanurate expressed by the formula (1) [the asterisked carbon (*) is asymmetric; R2 is H or a 1-36C organic residue which may contain one or more atoms selected from a group comprising O, S, N, and P] with a compound expressed by the formula (2): R1XH (R1 is a 1-36C organic residue which may contain one or more atoms selected from a group comprising O, S, N, and P; X is O, NR3, PR3 or S; and R3 is H or a 1-36C organic residue which may contain one or more atoms selected from a group comprising O, S, N, and P) to obtain the optically active oxazolidinone compound expressed by the formula (3).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a β-blocker,
The present invention relates to a method for producing an optically active oxazolidinone compound from an optically active tris- (2,3-epoxyalkyl) -isocyanurate compound, which is useful as an intermediate for producing an oxazolidinone antibacterial agent or the like.

[0002]

2. Description of the Related Art Tetrahedro
n) Volume 43, Issue 11, p. 2505 (1987)
Although a method for synthesizing an optically active oxazolidinone compound is described, the method is long and is not always an effective production method.

[0003] Tetrahedron Letters
edron Letters) 37, 44, 793
On page 7 (1996), a method for producing an optically active oxazolidinone compound is described. However, since a strong base such as butyllithium and twice the amount of a chiral epoxy compound are used, the method is not necessarily effective. Not a manufacturing method.

[0004] Chemistry Letters (Chemist
ry Letters), p. 1245 (1991), also describes a method for obtaining a chiral oxazolidinone from chiral glycidol and benzyl isocyanate. The compound obtained by this method is a 4-hydroxymethyl compound, and the compound of the present invention is obtained. Is different from

[0005] Tetrahedro
n) Vol. 54, No. 14, p. 3465 (1998)
A method for producing racemic oxazolidinone from N- (2,3-epoxypropyl) -carbamate and amines is disclosed in Tetrahedro Letters (Tetrahedro).
n Letters) 12, p. 809 (1971)
), A method for producing racemic oxazolidinone from phenylglycidyl ether and isocyanate
Although it is described, the optically active substance is not described.

US Pat. No. 3,446,814 discloses racemic tris- (2,3-epoxypropyl).
A method for producing oxazolidinone from isocyanurate and phenols has been described, but a method for producing optically active oxazolidinone from optically active tris- (2,3-epoxypropyl) -isocyanurate has been known. Not.

It is known that oxazolidinone compounds are easily converted to amino alcohol by hydrolysis. For example, Journal of Organic Chemistry (Journal of Organic Chemistry)
mistry), Vol. 62, No. 13, page 4449 (19
1997), and the Journal of American Chemistry (Journal of American Ch.
Emistry), vol. 105, p. 4499 (1983)
Year).

[0008]

An object of the present invention is to provide a method for easily producing an optically active oxazolidinone compound which is useful as an intermediate for producing a β-blocker, an oxazolidinone antibacterial agent and the like. The oxazolidinone compound of the present invention can be easily converted to an aminopropanol derivative as the above-mentioned production intermediate by hydrolysis. Beta-blockers are used in a wide range of treatments, including the treatment of angina and arrhythmias, as well as hypertension, hypothyroidism, pheochromocytoma, cardiovascular disease, neuropsychiatry, and anesthesiology Have been. In addition, Linezolid (trade name: Z, an oxazolidinone antibacterial agent)
Yvox) is known to exhibit high efficacy against microbial infections caused by vancomycin-resistant staphylococci, streptococci, anaerobic bacteria and tuberculosis bacteria.

The inventors of the present invention have conducted various studies to solve the above problems, and as a result, have found that an optically active tris- (2,3-epoxyalkyl) -isocyanurate compound and phenols, thiophenols and anilines can be used. The inventors have found that by reacting in the presence of a base, an optically active oxazolidinone compound useful as a production intermediate for a β-blocker, an oxazolidinone-based antibacterial agent or the like can be easily produced, and completed the present invention. The tris- (2,3-epoxyalkyl) -isocyanurate used as a raw material in the present invention has a relatively low purity of three asymmetric centers in one molecule and a relatively high purity due to good crystallinity. It is easy to react with phenols, thiophenols, and anilines, and has a characteristic that it can be easily obtained with high optical purity, and a high-purity oxazolidinone compound can be obtained under mild conditions.

[0010]

According to a first aspect of the present invention, there is provided formula (1):

[0011]

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[0012] optically active tris represented by - (2,3-epoxy alkyl) - isocyanurate, formula (2) R ¹
Formula (3) obtained by reacting a compound represented by XH:

[0013]

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(Wherein * represents an asymmetric carbon, X represents O, NR ³ , PR ³ , and S, and R ¹ is at least one member selected from the group consisting of O, S, N and P. Is an organic group having 1 to 36 carbon atoms which may include an atom of R, and R ² and R ³ are H or carbon atoms which may include at least one atom selected from the group consisting of O, S, N and P R ¹ , R ^2, and R ³ may be the same or different from each other.) A method for producing an optically active oxazolidinone compound represented by the following formula (A): Step and Step (B): Step (A): Optically active tris represented by the formula (1)
(2,3-epoxyalkyl) -isocyanurate;
The compound of the formula (2) is reacted with a compound represented by R ¹ XH to form a compound of the formula (4):

[0015]

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(Wherein * represents an asymmetric carbon, X represents O, NR ³ , PR ³ , and S, and R ¹ is at least one member selected from the group consisting of O, S, N and P. Is an organic group having 1 to 36 carbon atoms which may include an atom of R, and R ² and R ³ are H or carbon atoms which may include at least one atom selected from the group consisting of O, S, N and P R ¹ , R ^2, and R ³ may be the same or different, respectively.) And an adduct of tris- (2,3-epoxyalkyl) -isocyanurate represented by the formula: Obtaining step, and step (B): the optically active tris obtained in step (A).
A process for decomposing an adduct of (2,3-epoxyalkyl) -isocyanurate, a method for producing an optically active oxazolidinone compound represented by the formula (3). The method for producing an optically active oxazolidinone compound according to the second aspect in which an acid, an inorganic salt, an inorganic oxide or an onium salt is added. As a fourth aspect, a method using a base or an onium salt as a catalyst in the step (B). The method for producing an optically active oxazolidinone compound according to the aspect, the fifth aspect, the method for producing an optically active oxazolidinone compound according to any one of the first to fourth aspects, wherein R ² is hydrogen, and the sixth aspect. 7. The method for producing an optically active oxazolidinone compound according to any one of the first to fifth aspects, wherein X is an oxygen atom;
As a viewpoint, the method for producing an optically active oxazolidinone compound according to any one of the first to fifth aspects wherein X is NR ³ , and as an eighth aspect, X is O and R ¹ is substituted. The method for producing an optically active oxazolidinone compound according to any one of the first to fifth aspects, which is an aromatic ring or a heterocyclic ring which may be substituted, as a ninth aspect, X is NH; process for producing a ¹ first aspect to optically active oxazolidinone compound according to any one of the fifth aspect is a heterocyclic be aromatic ring or substituted optionally substituted, a tenth aspect, R ^Two
Is hydrogen, and the method for producing an optically active oxazolidinone compound according to any one of the first to fifth aspects, wherein X is an oxygen atom. As an eleventh aspect, R ² is hydrogen and X is The method for producing an optically active oxazolidinone compound according to any one of the first to fifth aspects which is NH, and as a twelfth aspect, a formula (N) obtained in the production process according to any one of the second to eleventh aspects Formula (5) obtained by hydrolyzing the compound of 4):

[0017]

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(In the above formula, * indicates an asymmetric carbon, X indicates O, NR ³ , PR ³ , and S, and R ¹ is at least one member selected from the group consisting of O, S, N and P. Is an organic group having 1 to 36 carbon atoms which may include an atom of R, and R ² and R ³ are H or carbon atoms which may include at least one atom selected from the group consisting of O, S, N and P 1 to 36, wherein R ¹ , R ² and R ³ may be the same or different.) A method for producing an optically active amino alcohol compound represented by the following formula: It is a method for producing an optically active amino alcohol compound represented by the formula (5) obtained by hydrolyzing the compound of the formula (3) obtained in any one of the viewpoints to the eleventh viewpoint.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION The formulas (2), (3),
In the compounds of (4) and (5), X is O, N
R ³ , PR ³ , and S are shown. R ¹ represents an organic group having 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of O, S, N and P. The organic group is not particularly limited, but is preferably an alkyl group, an aliphatic hydrocarbon group such as a cycloalkyl group, an optionally substituted aromatic hydrocarbon group, a heterocyclic ring, an alkoxycarbonylalkyl group, or the like. Is exemplified. R ¹ is an organic group having 1 to 36 carbon atoms, and preferably an organic group having 1 to 18 carbon atoms.

R ² and R ³ are H or O, S, N and P
And represents an organic group having 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of The organic group is not particularly limited, but preferably includes an aliphatic hydrocarbon group such as an alkyl group and a cycloalkyl group, an aromatic hydrocarbon group, a heterocycle, and an alkoxycarbonylalkyl group. C 1-36 consisting of the atomic groups exemplified above
And preferably an organic group having 1 to 18 carbon atoms.

More specifically, R ¹ , R ² and R ³ will be exemplified.

For example, as the alkyl group, a methyl group,
Examples of the cycloalkyl group include an ethyl group and a propyl group, and examples thereof include a cyclopropyl group, a cyclopentyl group, and a cyclohexyl group.

Examples of the aromatic hydrocarbon group include phenyl and naphthyl.

Examples of the heterocycle include indole, benzothiophene, 1,2,5-thiadiazole, pyridine and the like.

Examples of the alkoxycarbonylalkyl group include a methoxycarbonylmethyl group and an ethoxycarbonylethyl group.

The organic group is one selected from a halogen, an alkyl group, a cycloalkyl group, an alkylamino group, an alkoxy group, an alkylthio group, a cyano group, a nitro group, an alkoxycarbonyl group, a hydroxyl group and an amino group. It may have the above substituents, and the substituents may be the same or different.

Next, the method for producing the compound of the present invention will be described below.

The preferred method for producing the optically active oxazolidinone compound represented by the formula (3) according to the present invention comprises, as the step (A), an optically active tris- (epoxyalkyl) -isocyanurate represented by the formula (1): The phenols and anilines represented by the formula (2) are reacted to obtain an optically active tris- (epoxyalkyl) -isocyanurate adduct represented by the formula (4). It is a method of decomposing things.

The optically active tris- (2,3-epoxyalkyl) isocyanurate used as a raw material in the present invention easily reacts with the compound represented by the formula (2) R ¹ XH and has a high purity under mild conditions. The optically active oxazolidinone compound can be obtained.

Formula (1), which is a starting material of the present method, is represented by (2)
R, 2R ', 2R ") or (2S, 2S', 2S")
And the production method thereof is not particularly limited. For example, there are asymmetric epoxidation of olefin of tris (alkylallyl) isocyanurate and an asymmetric resolution method in which a racemate is kinetically resolved by an enzyme or the like. For example, optically active tris- (2,3-epoxypropyl) -isocyanurate reacts an optically active epichlorohydrin with cyanuric acid, and subsequently, a dehydrochlorination reaction is caused by dropping an aqueous NaOH solution while refluxing dehydration. , The optically active tris which is the target
(2,3-Epoxypropyl) -isocyanurate can be obtained.

As the optically active tris- (2,3-epoxyalkyl) isocyanurate used as a raw material in the present invention, R ² is a hydrogen atom or a lower alkyl group such as a methyl group or an ethyl group. − (2,3-
Epoxypropyl) -isocyanurate and tris (2,3-epoxypropyl-2-methyl) isocyanurate can be exemplified.

In the process of the present invention, when R ² is a hydrogen atom, that is, when tris- (2,3-epoxypropyl) -isocyanurate is used, the compound easily reacts with the compound represented by the formula (2) and is mild. It is most preferable because a highly pure optically active oxazolidinone compound can be obtained under the conditions.

Optically active tris used in the present invention
(2,3-epoxyalkyl) -isocyanurate is
It is preferable that the purity is high due to the nature of the use, specifically, the purity is preferably 90% or more, more preferably 95%.
That is all. The optical purity of the raw material is important because it affects the optical purity of the target substance, and is preferably 80%.
e. e. As described above, more preferably, the optical purity is 90% e. e.
That is all.

Although there is no particular limitation on the method of purification, for example, optically active tris- (2,3-epoxypropyl) -isocyanurate can be purified by recrystallization using a solvent such as methanol. It is possible to purify.

In the above formula, R ¹ is a phenyl group as an aromatic hydrocarbon group, a naphthyl group as an organic group comprising a heterocyclic ring, indole, benzothiophene, 3,4-dihydro-
Those having a skeleton of 2 (1H) -quinolinone, pyridine or the like are preferable.

It is desirable that the steps (A) and (B) are diluted with a solvent and reacted under milder conditions. The solvent may be inert to the reaction, for example, toluene,
Aromatic hydrocarbons such as chlorobenzene, dioxane, dimethoxyethane, ethers such as tetrahydrofuran,
Methanol, ethanol, 2-methoxyethanol, 2
Alcohols such as ethoxyethanol, halogenated hydrocarbons such as dichloroethane and chloroform, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, and tertiary compounds such as pyridine and triethylamine.
Secondary amines, amides such as N, N-dimethylformamide, sulfur compounds such as dimethylsulfoxide, nitro compounds such as nitroethane and nitrobenzene, esters such as ethyl acetate, water, and mixtures thereof are used. The reaction temperature can be between -78 ° C and the boiling point of the solvent. Preferably, the reaction is performed between room temperature (20 ° C.) and the boiling point of the solvent. In addition, these solvents can be used using a solvent in which the steps (A) and (B) are the same, or using different solvents.

Accordingly, the present invention provides a first method in which the steps (A) and (B) are carried out continuously, and the step (A) in which the adduct (4) is isolated and purified, and then purified with a preferred solvent (B). There is a second method of performing the step.

The compound of the formula (2) which is one of the starting materials used in the production method of the present invention includes, for example, phenol, naphthol, guaiacol (2-methoxyphenol),
-Cyclopentylphenol, aniline, 3-fluoro-4-morpholinoaniline, 3-hydroxy-4-morpholino-1,2,5-thiadiazole, thiophenol, diphenylphosphite, and the like, but the invention is not limited thereto. It is not limited.

The amount of the formula (2) used in the present invention is not particularly limited, but is preferably 3 to 1 mol of tris- (2,3-epoxyalkyl) -isocyanurate.
It is used in the range from mol to 100 mol, more preferably from 3 mol to 30 mol.

In the step (A) of reacting the optically active tris- (epoxyalkyl) -isocyanurate of the formula (1) with a phenol or aniline represented by the formula (2), a catalyst may be used if necessary. Can be. It can use any catalyst that promotes the reaction of the epoxy compound. For example, examples of the acid catalyst include Lewis acids such as aluminum chloride, tin chloride, boron trifluoride, and 3 (trifluoromethanesulfonic acid) ytterbium. In addition, inorganic salts such as sodium bromide, lithium bromide and calcium chloride, inorganic oxides such as titanium oxide and silica, and onium salts such as tetraethylammonium bromide and triphenylethylphosphonium bromide can be mentioned. .

On the other hand, the catalyst used in the step B for decomposing the optically active tris- (epoxyalkyl) -isocyanurate adduct represented by the formula (4) is preferably a basic substance or an onium salt. . These can be used alone or in combination.

Examples of the basic substance include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
Inorganic bases such as sodium bicarbonate and potassium bicarbonate,
Metal hydrides such as sodium hydride, metal alkoxides such as potassium t-butoxide, organometallic amides such as lithium diisopropylamide, organometallic compounds such as n-butyllithium pyridine, 4-dimethylaminopyridine, triethylamine, diethylisopropylamine, An organic base such as dimethylbenzylamine can be used.
Preferably, an inorganic base such as sodium hydroxide or potassium hydroxide, or an organic base such as dimethylbenzylamine is used.

The onium salt used in the present invention is
Examples thereof include ammonium salts, phosphonium salts, arsonium salts, stibonium salts, oxonium salts, sulfonium salts, selenonium salts, stannonium salts, and iodonium salts. Among them, the use of a quaternary ammonium salt or a tertiary sulfonium salt is preferable because side reactions can be suppressed, and quaternary ammonium salts can be reacted under mild conditions and have relatively good yield and purity. Is particularly preferred because

Next, onium salts used in the present invention will be specifically exemplified. Preferred as the quaternary ammonium salt are, for example, triethylbenzylammonium halide, triethylbenzylammonium halide, trioctylmethylammonium halide, tributylbenzylammonium halide, trimethylbenzylammonium halide, tetramethylammonium halide, halogen And tetrabutylammonium halide. Furthermore, 1,8-diaza-8-benzylbicyclo (5,4,0) undecene-7, 1,5-diaza-bicyclo (4,3,0) nonene-5 or 1-methylimidazole, 1-benzylimidazole and the like Also preferred are ammonium salts obtained by reacting an imidazole compound or an amine compound such as pyridine or a substituted pyridine represented by picoline with a halogenated hydrocarbon such as benzyl halide, methyl halide or ethyl halide. Examples of such catalysts include:

Preferred examples of the quaternary phosphonium salt include tetraalkylphosphonium halides such as tetra-n-butylphosphonium halide and tetra-n-propylphosphonium halide, and triethylbenzylphosphonide halide. Trialkylbenzylphosphonium halides, such as triphenylbenzylphosphonium halide, triphenylmethylphosphonium halide, triphenylethylphosphonium halide, etc. Examples thereof include halogenated tetraphenylphosphonium, halogenated tolylyl monoarylphosphonium, and halogenated tolylyl monoalkylphosphonium.

As an example of the halogen used as a counter ion of the onium salt in the present invention, a chlorine ion (C
l ^-), a bromine ion (Br ^-), iodide ion (I ^-) or the like can be exemplified as suitable. The quaternary ammonium salt can be converted to a hydroxyl group (OH ⁻ ) by treating it with an alkali such as NaOH to form a base, which can also be preferably used.

When the steps (A) and (B) are performed continuously, the compound of the formula (1), the compound of the formula (2) and the catalyst used in the step (B) are simultaneously added to a solvent. Can react.

In one specific embodiment of the present invention, X is an oxygen atom in the optically active tris- (2,3-epoxyalkyl) -isocyanurate of the formula (1) and the compound of the formula (2). By reacting a hydroxyl group-containing compound with a base or an onium salt, an optically active oxazolidinone compound in which X is an oxygen atom in the formula (3) can be produced.

The optically active tris- (2,2) of the formula (1)
3-epoxyalkyl) -isocyanurate is reacted with an amine compound in which X is NR ³ (particularly NH) in the compound of the formula (2) in the presence of a base or an onium salt. An optically active oxazolidinone compound in which X is NR ³ (particularly NH) can be produced.

The optically active tris of the formula (1)
In (2,3-epoxyalkyl) -isocyanurate, optically active tris- (2,3) in which R ² is a hydrogen atom
-Epoxypropyl) -isocyanurate and formula (2)
A compound having a hydroxyl group or an amino group, wherein X is an oxygen atom or NH, in the presence of a base or an onium salt, and also in the formula (3), X is an oxygen atom or N
An optically active oxazolidinone compound consisting of H can be produced.

In a particularly preferred embodiment, the optically active tris- (2,3-epoxypropyl) -isocyanurate of the formula (1) is used in a solvent in the presence of a phenol or aniline of the formula (2) and a base or an onium salt. The optically active oxazolidinone compound of the formula (3) can be synthesized by the following reaction.

In the present invention, the step (C) of hydrolyzing the adduct of tris- (2,3-epoxyalkyl) -isocyanurate of the formula (4) obtained in the step (B) is carried out to carry out the step (5) ) Is obtained.

Further, a step (C ′) of hydrolyzing the optically active oxazolidinone compound represented by the formula (3) is carried out,
An optically active amino alcohol represented by the formula (5) is obtained.

The catalyst used in the steps (C) and (C ') includes a basic substance or an acidic substance. Examples of the basic substance include inorganic bases such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate, and cesium carbonate, sodium methoxide, sodium ethoxide, and potassium t-type. Organic bases such as metal alkoxides such as butoxide, pyridine, 4-dimethylaminopyridine, triethylamine, diethylisopropylamine, and dimethylbenzylamine can be used.
Preferably, an inorganic base such as sodium hydroxide or potassium hydroxide is used. Examples of the acidic substance include inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, and nitric acid, organic acids such as formic acid, acetic acid, methanesulfonic acid, trifluoroacetic acid, and trifluoromethanesulfonic acid, Nafion, and Amberlyst. And other cation exchange resins.

As the solvent in the steps (C) and (C ′), the same solvent as the solvent used in the steps (A) and (B) can be used.

[0056]

EXAMPLES Next, the contents of the present invention will be described specifically with reference to examples, but the present invention should not be limited to these.

Example 1 Preparation of (5R) -5- (1-naphthyloxymethyl) -oxazolidin-2-one 140 mg of powdery potassium hydroxide, (2R, 2R ′, 2
R ")-Tris- (2,3-epoxypropyl) -isocyanurate (optical purity 99% ee or more) 6.18
g, 9.0 g of α-naphthol to 50 g of monochlorobenzene.
Then, the mixture was heated and refluxed with stirring. After reacting for 2 hours, the mixture was allowed to cool to room temperature, and the generated crystals were collected by filtration. The crystals were washed with ethanol and dried to obtain 13.38 g of the title compound.
(Melting point: 157.6-158.0 ° C, yield: 88%) was obtained as white crystals.

The specific rotation of the above crystal is [α] _D ²⁰ -1
3.96 ° (c = 0.80, EtOH).

The literature values of the title compound are as described in Tetrahedron, Vol.
According to page 05 (1987), [α] _D -12.1 °
(C = 0.46, EtOH).

Example 2 Preparation of (5S) -5- (1-naphthyloxymethyl) -oxazolidin-2-one 30 mg of powdery potassium hydroxide, (2S, 2S ′, 2
S ")-Tris- (2,3-epoxypropyl) -isocyanurate (optical purity 99% ee or more) 1.02
g, 1.5 g of α-naphthol and 20 parts of monochlorobenzene.
Then, the mixture was heated and refluxed with stirring. After reacting for 2 hours, the mixture was allowed to cool to room temperature, and the generated crystals were collected by filtration. The crystals were washed with ethanol and dried to give the title compound (2.04 g).
(Melting point: 156.2-156.6 ° C., yield: 81%) was obtained as white crystals.

The specific rotation of the above crystal is [α] _D ²⁰ +1
3.25 ° (c = 0.80, EtOH).

The literature values of the title compound are as described in Tetrahedron, Vol.
According to page 05 (1987), [α] _D + 12.2 °
(C = 0.80, EtOH).

Example 3 Preparation of (5S) -5- (phenylaminomethyl) -oxazolidine-2-one Step A): (2S, 2S ′, 2
Preparation of S ")-tris- (2-hydroxy-3-phenylaminopropyl) -isocyanurate In 11.2 g of aniline and 10 ml of ethanol were added (2S, 2
1.2 g of S ′, 2S ″)-tris- (2,3-epoxypropyl) -isocyanurate (having an optical purity of 99% ee or more) was added, and the mixture was stirred at room temperature for one day. Excess aniline was removed, and the obtained crude product was subjected to column chromatography (CHCl ₃ / MeOH = 98).
/ 2) to give 1.9 g (yield 81%) of the title compound as a glassy compound.

¹ H-NMR (ppm, CDCl ₃ ): 3.
07 (dd, 1H, J = 13 Hz, 5 Hz), 3.18
(Dd, 1H, J = 13 Hz, 3 Hz), 3.54 (b
s, 2H), 3.88 (d, 1H, J = 11 Hz),
4.05-4.23 (m, 2H), 6.60 (d, 1
H, J = 8 Hz), 6.72 (t, 1H, J = 8H)
z), 7.15 (t, 1H, J = 8 Hz) Step B): (5S) -5- (phenylaminomethyl)-
Preparation of oxazolidin-2-one 0.6 g of (2S, 2S ′, 2S ″)-tris- (2-hydroxy-3-phenylaminopropyl) -isocyanurate, 0.2 ml of sodium hydroxide in 8 ml of ethanol
g was added and heated to reflux with stirring. After reacting for 1 hour, the mixture was allowed to cool to room temperature, neutralized with 1N hydrochloric acid, and the solvent was distilled off. After removing insolubles with ethanol, the mixture was concentrated to obtain a crude product. The crude product was washed with ethyl acetate to give 0.32 of the title compound.
g (melting point 161.2-161.7 ° C, yield 53%) as white crystals. [Α] _D ²⁰ -15.6 ° (c = 0.
11, EtOH).

¹ H-NMR (ppm, CDCl ₃ + DMS
Od-6): 2.97-3.20 (m, 2H), 3.2
0-3.38 (m, 2H), 3.78-3.90 (m, 2H)
1H), 4.60 (bs, 1H), 6.11 (bs, 1
H), 6.61 (d, 1H, J = 8 Hz), 6.62
(T, 1H, J = 8 Hz), 7.11 (t, 1H, J =
Example 4 (2S) -1- (1-naphthyloxy) -3-amino-
Preparation of 2-propanol 2.43 g of (5S) -5- (1-naphthyloxymethyl) -oxazolidin-2-one, 10 ml of ethanol and 10 ml of water were added with 1.7 g of sodium hydroxide,
The mixture was heated under reflux with stirring. After reacting for 2 hours, the solvent was distilled off, and 1N-HCl ethyl acetate was added and stirred. In the water layer,
After adding 1N-NaOH to make the mixture slightly alkaline, the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain 1.25 g of the desired product (yield: 52%).
The melting point is 121 to 122 ° C, and [α] _D ²⁰ -12.5
° (c = 1.0, 95% EtOH). (Literature value [α] _D -11.0 ° (c = 0.86, EtO
H)).

¹ H-NMR (ppm, CDCl 3):
2.27 (bs, 3H), 2.90-3.00 (m, 1
H), 3.00-3.10 (m, 1H), 4.02-
4.20 (m, 3H), 6.75-6.85 (m, 1
H), 7.30-7.55 (m, 4H), 7.75-
7.85 (m, 1H), 8.20-8.30 (m, 1
H)

[0067]

According to the present production method, an optically active oxazolidinone compound useful as an intermediate for production of a β-blocker or the like can be easily produced from an optically active tris- (epoxyalkyl) -isocyanurate compound as a raw material. can do.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) // C07B 61/00 300 C07B 61/00 300 C07M 7:00 C07M 7:00 (72) Inventor Kazutaka Arai 3-7-1, Kandanishikicho, Chiyoda-ku, Tokyo F-term (reference) in Nissan Chemical Industry Co., Ltd. 4C056 AA01 AB01 AC02 AD01 AE02 AF01 BB04 4H006 AA02 AC41 AC52 AC81 BA02 BA09 BA10 BA11 BA28 BA29 BA30 BA32 BA37 BA44 BA50 BA52 BA53 BA66 BA67 BB11 BB12 BB15 BB17 BB19 BB21 BB22 BB23 BB25 BC10 BJ50 BN10 BP30 BU32 4H039 CA42 CA60 CA71 CG30 CH60

Claims (13)

[Claims] (1) Formula (1): Formula (3) obtained by reacting an optically active tris- (2,3-epoxyalkyl) -isocyanurate represented by the formula (2) with a compound represented by R ¹ XH: (In the above formula, * represents an asymmetric carbon, and X represents O, NR ³ , P
R ³ and S are shown, wherein R ¹ has 1 to 1 carbon atoms which may contain one or more atoms selected from the group consisting of O, S, N and P.
36 is an organic group, and R ² and R ³ are H or O, S,
It represents an organic group having 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of N and P, and R ¹ , R ² and R ³ may be the same or different. A method for producing an optically active oxazolidinone compound represented by the formula: 2. The following steps (A) and (B): (A) step: an optically active tris represented by the formula (1):
(2,3-epoxyalkyl) -isocyanurate;
The compound represented by the formula (2) is reacted with a compound represented by R ¹ XH to form a compound represented by the formula (4): (In the above formula, * represents an asymmetric carbon, and X represents O, NR ³ , P
R ³ and S are shown, wherein R ¹ has 1 to 1 carbon atoms which may contain one or more atoms selected from the group consisting of O, S, N and P.
36 is an organic group, and R ² and R ³ are H or O, S,
It represents an organic group having 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of N and P, and R ¹ , R ² and R ³ may be the same or different. A) obtaining an adduct of tris- (2,3-epoxyalkyl) -isocyanurate; and (B) step: the optically active tris- obtained in step (A).
A process for decomposing an adduct of (2,3-epoxyalkyl) -isocyanurate, the method comprising the steps of: producing an optically active oxazolidinone compound represented by the formula (3). 3. The method for producing an optically active oxazolidinone compound according to claim 2, wherein a Lewis acid, an inorganic salt, an inorganic oxide or an onium salt is added as a catalyst to the step (A). 4. The method for producing an optically active oxazolidinone compound according to claim 2, wherein a base or an onium salt is used as a catalyst in the step (B). 5. The method according to claim 1, wherein R ² is hydrogen.
The method for producing an optically active oxazolidinone compound according to any one of the above. 6. The method for producing an optically active oxazolidinone compound according to claim 1, wherein X is an oxygen atom. 7. The method according to claim 1, wherein X is NR ^3.
The method for producing an optically active oxazolidinone compound according to any one of the above. 8. The optical activity according to claim 1, wherein X is O, and R ¹ is an optionally substituted aromatic ring or an optionally substituted heterocyclic ring. A method for producing an oxazolidinone compound. 9. The optical activity according to claim 1, wherein X is NH, and R ¹ is an optionally substituted aromatic ring or an optionally substituted heterocyclic ring. A method for producing an oxazolidinone compound. 10. The method for producing an optically active oxazolidinone compound according to claim 1, wherein R ² is hydrogen and X is an oxygen atom. 11. The method for producing an optically active oxazolidinone compound according to claim 1, wherein R ² is hydrogen and X is NH. 12. The method according to claim 2, wherein
Formula (5) obtained by hydrolyzing the compound of the formula (4) obtained in the production process of the item: (In the above formula, * represents an asymmetric carbon, and X represents O, NR ³ , P
R ³ and S are shown, wherein R ¹ has 1 to 1 carbon atoms which may contain one or more atoms selected from the group consisting of O, S, N and P.
36 is an organic group, and R ² and R ³ are H or O, S,
It represents an organic group having 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of N and P, and R ¹ , R ² and R ³ may be the same or different. A method for producing an optically active amino alcohol compound represented by the formula: 13. The method according to claim 1, wherein
A method for producing an optically active amino alcohol compound represented by the formula (5) obtained by hydrolyzing the compound of the formula (3) obtained in the above section.