WO2001016118A1 - Processes for the preparation of optically active oxazolidinone compounds - Google Patents

Abstract

A process for preparing optically active oxazolidinone compounds useful as intermediates for the preparation of β blocker from optically active tris(2,3-epoxyalkyl) isocyanurate compounds. Specifically, a process of reacting an optically active tris(2,3-epoxyalkyl) isocyanurate represented by general formula (1) with a compound represented by general formula (2): R1XH and thus obtaining an optically active oxazolidinone compound represented by general formula (3).

Description

 Description Method for producing optically active oxazolidinone compound

 The present invention provides an optically active oxazolidinone compound, which is useful as an intermediate for the production of / 9-blockers, oxazolidinone antibacterial agents, etc., from an optically active tris- (2,3-epoxyalkyl) -isocyanurate compound. How to do it. Background art

 Tetrahedron, vol. 43, No. 11, page 2505 (1989) describes a method for synthesizing optically active oxazolidinone compounds, but the process is long and not necessarily effective. It cannot be said that it is a simple manufacturing method.

 Tetrahedron Letters, Vol. 37, No. 44, pp. 7937 (1996), describes a method for producing an optically active oxazolidinone compound, but the method for producing an optically active oxazolidinone compound is described. The use of a base and twice the amount of a chiral epoxy compound, which is not always an effective method of production, is described in Chemistry Letters, page 1245 (1991). A method for obtaining chiral oxazolidinone from glycidol and benzyl isocyanate is described, but the compound obtained by this method is a 4-hydroxymethyl form, which is different from the compound of the present invention.

 Tetrahedron, Vol. 54, No. 14, pp. 3465 (1998) states that N- (2,3-epoxypropyl) carbamate and racemic oxazolidino from amines. The method for producing styrene is described in Tetrahedron Letters, No. 12, p. 809 (1971), as a racemic material from phenyldaricidyl ether and isocyanate. A method for producing oxazolidinone is described, but no description is given for an optically active substance.

Also, US Pat. No. 3,446,814 discloses a racemic trisux (2,3- A method for producing oxazolidinone from monoisocyanurate and phenols has been described. So far, optically active oxazolidinone has been produced from optically active tris- (2,3-epoxypropyl) isocyanurate. There is no known method.

 It is known that oxazolidinone compounds are easily converted to amino alcohol by hydrolysis. For example, Journal of Organic Chemistry), Vol. 62, No. 13, page 4449 (1997), and Journal of American Chemistry. I (J ournalof Am erican C hemistry)

It is described in Vol. 105, p. 499 (1983).

 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 an i-blocker or an oxazolidinone antibacterial agent. The oxazolidinone compound of the present invention can be easily converted to the above-mentioned production intermediate aminopropanol derivative by hydrolysis. -Broc is a wide-ranging therapeutic drug from the treatment of angina and arrhythmias, to hypertension, thyroid dysfunction, pheochromocytoma, cardiovascular disease, neuropsychiatry and anesthesia. Has been used as In addition, the oxazolidinone antibacterial agent Linez 0

11d (trade name: Zyvox) is known to have high efficacy against microbial infections caused by noncomycin-resistant staphylococci, streptococci, anaerobic bacteria and tuberculosis bacteria.

The present inventors have conducted various studies to solve the above problems, and as a result, have found that an optically active tris (2,3-epoxyalkyl) monoisocyanurate compound and phenols, thiophenols, and anilines can be used in the presence of a base. The present inventors have found that an optically active oxazolidinone compound useful as an intermediate for the production of β-blocker and oxazolidinone-based antibacterial agents and the like can be easily produced by reacting the compound with the compound (1), thereby completing the present invention. Tris- (2,3-epoxyalkyl) monoisocyanurate used as a raw material in the present invention has a relatively small number of asymmetric centers, three in a molecule, and has relatively high purity due to good crystallinity. It is easy to react with phenols, thiophenols, and anilines, and has a mild and mild optically available characteristic. High purity oxazolidinone compound can be obtained under the conditions, disclosure of the invention

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

で表される光学活性トリス一 （2 , 3—エポキシアルキル） 一イソシァヌレー ト と、 式 （2) R 'XHで表される化合物とを反応して得られる、 Equation (1)

Which is obtained by reacting an optically active tris- (2,3-epoxyalkyl) -isocyanurate represented by the formula (2) with a compound represented by the formula (2) R′XH,

Equation (3):

Expression (3

(In the above formula, * indicates an asymmetric carbon, X indicates 0, NR ³ , PR ³ , and S, and R ¹ is at least one atom selected from the group consisting of 0, S, N, and P Is an organic group having 1 to 36 carbon atoms, wherein R ² and R ³ are H or carbon atoms which may contain one or more atoms selected from the group consisting of 0, S, N and P R ′, R ² and R ³ may be the same or different, each representing an organic group of 1 to 36.) A method for producing an optically active oxazolidinone compound represented by the formula:

 As a second viewpoint, the following (A) process and (B) process:

Step (A): An optically active tris (2,3-epoxyalkyl) represented by the formula (1) A) reacting one isocyanurate with a compound represented by the formula (2) R'XH to obtain a compound represented by the formula (4):

Equation (4)

(In the above formula, * represents an asymmetric carbon, X represents 0, NR ³ , PR ³ , and S, and R ′ represents at least one atom selected from the group consisting of 0, S, N, and F. Is an organic group having 1 to 36 carbon atoms, wherein R ² and R ³ are H or 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of 0, S, N and P. R ', R ² and R ³ may be the same or different, respectively, to obtain a tris- (2,3-epoxyalkyl) -isocyanurate adduct represented by the formula: Process, and

 Step (B): a step of decomposing the optically active tris- (2,3-epoxyalkyl) -isocyanurate adduct obtained in step (A), comprising an optically active oxazolidinone represented by the formula (3): A method for producing a compound,

 As a third aspect, the method for producing an optically active oxazolidinone compound according to the second aspect, wherein a Lewis acid, an inorganic salt, an inorganic oxide, or an ionic salt is added as a catalyst to the step (A),

 As a fourth aspect, the method for producing an optically active oxazolidinone compound according to the second aspect, wherein a base or an ionic salt is used as a catalyst in the step (B),

As a 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,

As a sixth aspect, any one of the first to fifth aspects in which X is an oxygen atom A method for producing an optically active oxazolidinone compound according to the description,

Manufacturing method of the as seventh aspect, X is a first aspect to optically active Okisazorijinon compound of placing serial to any one of the fifth aspect is NR ^3,

As an eighth aspect, the optics according to any one of the first to fifth aspects, wherein X is 0 and R ¹ is an optionally substituted aromatic ring or an optionally substituted heterocyclic ring. A method for producing an active oxazolidinone compound,

As a ninth aspect, the optics according to any one of the first to fifth aspects, wherein X is NH and R ¹ is an optionally substituted aromatic ring or an optionally substituted heterocyclic ring. A method for producing an active oxazolidinone compound,

As a tenth aspect, there is provided a method for producing an optically active oxazolidinone compound according to any one of the first to fifth aspects, wherein R ² is hydrogen and X is an oxygen atom. A method for producing an optically active oxazolidinone compound according to any one of the first to fifth aspects, wherein R ² is hydrogen and X is NH; and, as a second aspect, a second aspect to a first aspect. Formula (5) obtained by hydrolyzing the compound of Formula (4) obtained in any one of the processes of the aspect:

H

 Equation (5)

¹

¹

(In the above formula, * represents an asymmetric carbon, X represents 0, NR ³ , PR ³ , and S, and R ¹ represents one or more atoms selected from the group consisting of 0, S, N, and P. An organic group having 1 to 36 carbon atoms which may be contained, wherein R ² and R ³ are H or 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of 0, S, N and P And RR ² and R ³ may be the same or different, respectively.) A method for producing an optically active amino alcohol compound represented by the formula:

 As a thirteenth aspect, a formula obtained from any one of the first to the first aspects is used.

This is a method for producing an optically active amino alcohol compound represented by the formula (5) obtained by hydrolyzing the compound (3). BEST MODE FOR CARRYING OUT THE INVENTION

In the compounds of the formulas (2), (3), (4) and (5) of the present invention, X represents 0, NR ³ , PR ³ , and S. 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 0, S, N and P. Force ⁵ is not particularly restricted but includes organic group, preferably an alkyl group, an aliphatic hydrocarbon group, cycloalkyl group, optionally substituted aromatic hydrocarbon group, heterocyclic, alkoxycarbonylalkyl And the like. R ′ is an organic group having 1 to 36 carbon atoms, including the atomic groups exemplified above, and is preferably an organic group having 1 to 18 carbon atoms.

R ² and R ³ represent H or an organic group having 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of 0, S, N and P. The organic group is not particularly limited, but is preferably an aliphatic hydrocarbon group such as an alkyl group or a cycloalkyl group, an aromatic hydrocarbon group, a heterocyclic ring, an alkoxycarbonylalkyl group, or the like. It is. It is an organic group having 1 to 36 carbon atoms comprising the atomic groups exemplified above, and preferably an organic group having 1 to 18 carbon atoms.

More specifically: ', R ² and R ³ are exemplified.

 For example, the alkyl group includes a methyl group, an ethyl group, a propyl group and the like, and the cycloalkyl group includes a cyclopropyl group, a cyclopentyl group and a cyclohexyl group.

 Examples of the aromatic hydrocarbon group include fuunyl and naphthyl.

 Heterocycles include indole, benzothiophene, 1,2,5-thiadiazol, pyridine and the like.

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

In addition, the above-mentioned organic group includes a halogen, an alkyl group, a cycloalkyl group, an alkylamino group, an alkoxy group, an alkylthio group, a cyano group, a nitro group, an alkoxyl group, a hydroxyl group, and an amino group. And may have one or more substituents selected from the group consisting of the same or different substituents. Next, a 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- (epoxyalkylene) -iso-isocyanurate represented by the formula (1): The phenols and anilines represented by (2) are reacted to obtain an optically active tris (epoxyalkyl) -isocyanurate adduct represented by the formula (4). This is a method of decomposing this adduct. 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'XH, and has a high purity optical property under mild conditions. An active oxazolidinone compound can be obtained. Formula (1), which is a starting material of the present method, represents a compound of (2R, 2R,, 2R ") or (2S, 2S ', 2S"). There is no particular limitation. For example, there are asymmetric epoxidation of tris (alkylaryl) isocyanurate and symmetric olefins, and asymmetric resolution method of kinetically resolving a racemic form with an enzyme or the like. _C For example, optically active tris (2,3_epoxypropyl) The isocyanurate is reacted with optically active epichlorohydrin on cyanolic acid, followed by the dropwise addition of an aqueous solution of NaOH while dehydrating and refluxing, whereby a dehydrochlorination reaction takes place, and the desired optically active tris (2) , 3-epoxypropyl) One isocyanurate can be obtained.

Examples of the optically active tris (2,3-epoxyalkyl) isocyanurate used as a raw material in the present invention include a hydrogen atom for R ² and a lower alkyl group such as a methyl group or an ethyl group. (2,3-epoxypropyl) monoisocyanurate and tris (2,3-epoxypropyl-12-methyl) isocyanurate can be exemplified.

Even when R ² is a hydrogen atom during the production process of the present application, 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 high purity optically active oxazolidinone compound can be obtained under the conditions.

The optically active tris- (2,3-epoxyalkyl) monoisocyanurate used in the present invention is preferably of high purity due to the nature of its use. The purity is preferably 0% or more, and more preferably 95% or more. The optical purity of the raw material is important because it affects the optical purity of the target substance, and is preferably S0% e.e. or more, more preferably 90% e.e. or more.

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

In the above formula, R ¹ is a fuunyl group or a naphthyl group as an aromatic hydrocarbon group, and indole, benzothiophene, 3,4-dihydro-12 (1H) 1 as an organic group comprising a heterocyclic ring. Those having a skeleton of quinolinone, pyridine or the like are preferred.

 It is desirable that the steps (A) and (B) are diluted with a solvent and reacted under milder conditions. The solvent only needs to be inert to the reaction. For example, aromatic hydrocarbons such as toluene and benzene, ethers such as dioxane, dimethyloxetane and tetrahydrofuran, methanol, ethanol, 2- Alcohols such as methoxyethanol and 2-ethoxyethanol; halogenated hydrocarbons such as dichloroethane and chloroform; ketones such as acetone and methyl ethyl ketone; nitriles such as acetonitrile; pyridine; Tertiary amines such as triethylamine, amides such as N, N-dimethylformamide, sulfur compounds such as dimethyl sulfoxide, nitrone compounds such as nitroethane and nitrobenzene, esters such as ethyl acetate, and water Alternatively, a mixture thereof is used. The reaction can be carried out at a temperature between 178 and the boiling point of the solvent. Preferably, it is carried out 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.

 Therefore, the present invention provides a first method in which the steps (A) and (B) are performed continuously, and a step (B) in a preferred solvent after the adduct (4) is isolated and purified in the step (A). The second method is mentioned.

Examples of the compound of the formula (2), which is one of the starting materials used in the process of the present invention, include phenol, naphthol, guaiacol (2-methoxyphenol), 2-cyclopentylphenol, aniline, and 3-fluoro-41-morpholinoa. Diphosphorus, 3-hydroxyl 4-morpholino 1, 2, 5-thiadiazol, chiopheno , Difuunilphosphite, and the like, but the present invention is not limited thereto.

 The amount of the formula (2) used in the present invention is not particularly limited, but is preferably from 3 to 100 mol per 1 mol of tris (2,3-epoxyalkyl) -isocyanurate. More preferably, it is used in the range of 3 mol to 30 mol. In the step (A) of reacting the optically active tris- (epoxyalkyl) -1-isocyanurate of the formula (1) with the phenols and anilines represented by the formula (2), a catalyst can be used if necessary. 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) ittibidium. In addition, inorganic salts such as sodium bromide, lithium bromide, and calcium chloride; inorganic oxides such as titanium oxide and silica; tetraethylammonium bromide; triphenylethylphosphonium bromide; Onion salt. .

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

 Examples of the basic substance include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate; metal hydrides such as sodium hydride; and potassium t. -Metal alkoxides such as butoxide; organometallic amides such as lithium diisopropylamide; organic metal compounds such as n-butyllithium; pyridine; 4-dimethylaminopyridine, triethylamine, and methyl isopropylamide And an organic base such as dimethylbenzylamine. Preferably, an inorganic base such as sodium hydroxide or hydroxylating sphere, or an organic base such as dimethylpentylamine is used.

Examples of the honium salt used in the present invention include an ammonium salt, a phosphonium salt, an arsonium salt, a stibonium salt, an oxonium salt, a sulfonium salt, a selenonium salt, a stannonium salt, and a jordonium salt. Fourth among them The use of a quaternary ammonium salt or a tertiary sulfonium salt is preferable because side reactions can be suppressed, and a quaternary ammonium salt can be reacted under mild conditions, and the yield and purity are relatively high. It is particularly preferable because a good product is obtained.

 Next, specific examples of onium salts used in the present invention are given.

Preferred as the quaternary ammonium salt are, for example, halogenated tribenzylbenzylammonium, norogendanitriethylbenzylammonium, nordogenidanitrioctylmethylammonium, and nordogenidhitritribenzylbenzylammonium. And halogenated trimethylbenzylammonium, halogenated tetramethylammonium, halogenated tetraethylammonium, halogenated tetrabutylammonium, and the like. 1,8-diaza-1 8-benzylbicyclo

(5,4,0) ndene-1,7,1,5-diazabicyclo (4,3,0) none-5 or imidazole, such as 1-methylimidazole, 1-benzylimidazole, etc. Ammonia obtained by reacting a compound such as an amine compound such as a substituted pyridine represented by pyridine, picoline or the like, with a halogenated hydrocarbon such as halogenated benzyl, methyl phenol, methylated chloro or the like. Salts can also be exemplified as suitable catalysts.

 Preferable quaternary phosphonium salts include halogenated tetraalkylphosphonium, such as halogenated tetra-n-butylphosphonium and halogenated tetra-n-propylphosphonium, and halogenated tetramethylphosphonate. Halogenated trialkyl benzylphosphonium, such as benzylbenzylphosphoric acid, halogenated triphenylmethylphosphonium, halogenated triphenylmethylphosphonium, etc. Alkylphosphonium, hydrogenated triphenylbenzylphosphonium, hydrogenated tetraphenylphosphonium, tritolyl monoarylphosphonated halide, or halogenated tritolylmonoalkylphosphonium Is mentioned.

Examples of the halogen used as a counter ion of the onium salt in the present invention include chloride ion (C 1−), bromide ion (Br—), and iodine ion (I—). it can. The quaternary ammonium salt can be converted to a hydroxyl group (OH—) by converting it with a hydroxyl group such as NaOH to form a base. Yes, and this can also be used as a preference.

 When step (A) and step (B) are performed consecutively, the compound of formula (1), the compound of formula (2) and the catalyst used in step (B) are added simultaneously to the solvent and reacted. Can be.

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

Further, the optically active tris- (2,3-epoxyalkyl) -isocyanurate of the formula (1) and an amine-based compound of the formula (2) wherein X is NR ³ (particularly NH) are used. The reaction is carried out in the presence of a base or an onium salt to produce an optically active oxazolidinone compound in which X is NR ³ (particularly NH) in formula (3).

Then, in the optically active tris- (2,3-epoxyalkyl) -isocyanurate of the formula (1), an optically active tris- (2,3-epoxypropyl) -isocyanurate in which R ² is a hydrogen atom, and the formula (2) In the compound of formula (3), a compound having a hydroxyl group or an amino group, wherein X is an oxygen atom or NH, is reacted in the presence of a base or onium salt. A zolidinone compound can be produced.

 In a particularly preferred embodiment, the optically active tris (2,3-epoxypropyl) monoisocyanurate in 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 oxime. By reacting in the presence of a salt, an optically active oxazolidinone compound of the formula (3) can be synthesized.

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

Further, the step (C) of hydrolyzing the optically active oxazolidinone compound represented by the formula (3) is carried out to obtain the optically active amino alcohol represented by the formula (5). Examples of the catalyst used in the steps (C) and (C,) include a basic substance and an acidic substance. Examples of the basic substance include inorganic bases such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, cesium carbonate, sodium methoxide, sodium methoxide, and potassium. Metal alkoxides such as t-butoxide, and organic bases such as pyridine, 4-dimethylaminopyridine, triethylamine, getyl isopropylamine, and dimethylpendiamine can be used. Preferably, an inorganic base such as sodium hydroxide and 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, naphthion, and amberlyst. Cation exchange resin can be used.

 In addition, the same solvent as used in the steps (A) and (B) can be used as the solvent in the steps (C) and (C,). Next, the content of the present invention will be specifically described with reference to examples, but the present invention should not be limited to these.

 Example 1

 Production of (5R) -1-5- (1-naphthyl xymethyl) oxazolidine-1-one

 Powdered potassium hydroxide 140 mg, (2R, 2R ', 2R ")-tris- (2,3-epoxypropyl) -isocyanurate (optical purity 99% e.e. or more) 6.1 50 ml of benzene with monochrome mouth was added to 8 g and 9.0 g of α-naphthol, and the mixture was heated and refluxed with stirring, allowed to react for 2 hours, allowed to cool to room temperature, and the resulting crystals were collected by filtration. After washing with water, drying was performed to obtain 13.38 g (melting point: 157.6 to 158.0, yield: 88%) of the title compound as white crystals.

The specific rotation of the crystal was [a] D ²⁰ -1 3.96 ° (c = 0.80, EtOH).

The literature value of the title compound is tetrahedron. According to Vol. 3, No. 1, pp. 2505 (1989). ]. It was 12.1 ° (c = 0.446, EtOH).

 Example 2

 Production of (5S) -5- (1-naphthyloxymethyl) oxazolidine-1-one

 Powdered potassium hydroxide 30mg, (2S, 2S ', 2S ")-tris-one (2,3-epoxypropyl) -isocyanurate (optical purity 99% e.e. Or more) 1.02g, a — To 1.5 g of naphthol was added 20 ml of benzene having a monochrome mouth, and the mixture was heated and refluxed with stirring, allowed to react for 2 hours, allowed to cool to room temperature, and the resulting crystals were collected by filtration. Thereafter, drying was performed to obtain 2.04 g (melting point: 156.2-156.6 ° C, yield: 81%) of the title compound as white crystals.

Specific rotation of the crystal was ^{[ «] D 20 + 1 3.} 2 5 ° (c = 0. 8 0, E t OH).

 The literature value of the title compound is [«] according to Tetrahedron (Vol. 43, No. 11, pp. 2505 (1989)). + 12.2 ° (c = 0.80, Et0H).

 Example 3

 (5S) — 5- (Phenylaminomethyl) oxazolidin-2-one Production Step A): (2S, 2S ', 2S ") — Tris-1 (2-hydroxy-3-phenyl) Production of minopropyl) isocyanurate

(2S, 2S ', 2S ")-tris- (2,3-epoxypropyl) -isocyanurate (optical purity 99% e.e. or more) in 11.2 g of aniline and 10 ml of ethanol ) 1. 2 g was added, day was. after the reaction stirred at room temperature, was removed under reduced pressure excess Aniri down, the resulting crude was purified by column chromatography _{(CHC 1 3 / M e OH} = 9 8X2) Then, 1.9 g (yield 81%) of the title compound was obtained as a glassy compound.

Ή -NR (p pm, C DC 1 3): 3. 0 7 (dd, 1 H, J = 1 3 H z, 5 H z), 3. 1 8 (dd, 1 H, J = 1 3 H z, 3 Hz), 3.54 (bs, 2 H), 3.88 (d, 1 H, J = ll Hz), 4.05-4.23 (m, 2 H), 6.60 (d, 1 H, J = 8 Hz), 6.72 (t, 1 H, J = 8 Hz), 7.15 (t, 1 H, J = 8 Hz) )

 Step B): Production of (5S) -5- (phenylaminomethyl) oxazolidin-12-one

(2S, 2S ', 2S ") — Tris (2-hydroxy-13-phenylaminopropyl) monoisocyanurate (0.6 g), ethanol (8 ml), sodium hydroxide (0.2 g), and stirring After heating for 1 hour, the reaction was allowed to cool to room temperature, neutralized with 1N hydrochloric acid, and the solvent was distilled off.The insoluble matter was removed with ethanol, followed by concentration to obtain a crude product. by the washing Ri title compound 0. 3 2 g in. - [.]. (melting point 1 6 1. 2 1 6 1. 7 ° C, yield 3%) as a white crystalline ² ° — 15.6 ° (c = 0.11, 1, E t OH) o

^{1 H - NM R (ppm,} CD C 1 3 + DMS O d - 6): 2. 9 7 - 3. 2 0 (m, 2 H), 3. 20 - 3. 3 8 (m, 2 H) , 3.78-3.90 (m, 1 H), 4.60 (bs, 1 H), 6.11 (bs, 1 H), 6.61 (d, 1 H, J = 8 Hz), 6.62 (t, 1H, J = 8Hz), 7.11 (t, 1H, J = 8Hz)

 Example 4

 (2 S) — 1— (1—naphthyloxy) 1-3-amino-2-propanol

2. Add 1.7 g of sodium hydroxide to 43 g of (5S) — 5— (1-naphthyloxymethyl) oxazolidine — 2-one, 10 ml of ethanol, and 10 ml of water. The mixture was heated under reflux with stirring. After reacting for 2 hours, the solvent was distilled off, and ethyl acetate 1N-HC1 was added and stirred. The aqueous layer was made weakly alkaline by adding 1 N—NaOH and then 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%). Melting point 1 2 1; a 1 2 2, [a] D 2 0 - was 1 2. 5 ° (c = 1. 0, 9 5% E t OH). (Literature value

 11.0 ° (c = 0.86, EtOH)).

Ή-NMR (ppm, C DC 13): 2.27 (bs, 3 H), 2.90-3.00 (m, 1 H), 3.00—3.10 (m, 1 H), 4.02-4.20 (m, 3 H), 6.75-6.85 (m, 1 H), 7.30—7.55 (m, 4 H), 7.75-7.85 (m, 1 H) , 8.20-8.30 (m, 1 H) Industrial applicability

 By this production method, an optically active oxazolidinone compound, which is useful as an intermediate for the production of /?-Blockers, etc., can be easily converted from an optically active tris- (epoxyalkyl) -iso cyanurate compound as a raw material. A method of manufacturing can be provided.

Claims

Claim formula (1): Expression (1

Which is obtained by reacting an optically active tris (2,3-epoxyalkyl) monoisocyanurate represented by the formula (2) with a compound represented by the formula (2) R'XH, Equation (3): Equation (3)

(In the above formula, * represents an asymmetric carbon, X represents 0, NR ³ , PR ³ , and S, and R ′ represents one or more atoms selected from the group consisting of 0, S, N, and P. An organic group having 1 to 36 carbon atoms which may be contained, wherein R ² and R ³ are H or 1 to 3 carbon atoms which may contain one or more atoms selected from the group consisting of 0, S, N and P R ′, R ² and R ³ may be the same or different.) A process for producing an optically active oxazolidinone compound represented by the formula: 2. Processes (A) and (B) below: Step (A): reacting the optically active tris- (2,3-epoxyalkyl) monoisocyanurate represented by the formula (1) with the compound represented by the formula (2) R'XH Equation (4): Expression (4

(In the above formula, * represents an asymmetric carbon, X represents 0, NR ³ , PR ³ , and S, and R ¹ represents one or more atoms selected from the group consisting of 0, S, N, and P. An organic group having 1 to 36 carbon atoms which may be contained, wherein R ² and R ³ are H or 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of 0, S, N and P R \ R ² and R ³ may be the same or different.) A process for obtaining an adduct of tris (2,3-epoxyalkyl) monoisocyanurate represented by the formula:  Step (B): a step of decomposing the optically active tris- (2,3-epoxyalkyl) -isocyanurate adduct obtained in step (A), comprising an optically active oxazolidinone compound represented by the formula (3): Manufacturing method.  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 ionic 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 ionic salt is used as a catalyst in the step (B). 5. The method for producing an optically active oxazolidinone compound according to any one of claims 1 to 4, wherein R ² is hydrogen.  6. The method for producing an optically active oxazolidinone compound according to any one of claims 1 to 5, wherein X is an oxygen atom. 7. method for producing X is optically active old Kisazorijinon compound according to any one of the range 1 to claims 5 according a NR ^3. 8. X is 0 and R ¹ is an optionally substituted aromatic ring or optionally substituted 6. The method for producing an optically active oxazolidinone compound according to any one of claims 1 to 5, which is a heterocyclic ring. 9. The optical activity according to any one of claims 1 to 5, 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 any one of claims 1 to 5, wherein R ² is hydrogen and X is an oxygen atom. 11. The method for producing an optically active oxazolidinone compound according to any one of claims 1 to 5, wherein R ² is hydrogen and X is NH.  1 2. Formula (5) obtained by hydrolyzing the compound of Formula (4) obtained in the production process of any one of Claims 2 to 11: Formula (5): Formula (5)

R ¹ (In the above formula, * represents an asymmetric carbon, X represents 0, NR ³ , PR ³ , and S, and R ¹ represents one or more atoms selected from the group consisting of 0, S, N, and P. An organic group having 1 to 36 carbon atoms which may be contained, wherein R ² and R ³ are H or 1 to 36 carbon atoms which may contain one or more atoms selected from the group consisting of 0, S, N and P 36, wherein RR ² and R ³ may be the same or different.) A method for producing an optically active amino alcohol compound represented by the formula:  1 3. An optically active amino alcohol compound represented by the formula (5) obtained by hydrolyzing the compound of the formula (3) obtained in the production process of any one of the claims 1 to 11 Manufacturing method.