JP2003277346A - Method for producing optically active sulfonamide compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a sulfonamide compound useful as an intermediate for synthesizing physiologically active, compounds such as medicines and the like in good enanthioselectivity. <P>SOLUTION: This method for producing the optically active sulfonamide compound comprises a process for reacting a ketone compound with hydroxylamine to produce the oxime compound, a process for subjecting the oxime compound to a sulfonylimination reaction to produce the sulfonimide compound, and an asymmetrical reduction process for reacting the obtained sulfonimide compound with a hydride reagent in the presence of an optically active cobalt complex catalyst. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for enantioselectively producing an optically active sulfonamide compound useful as a synthetic intermediate or drug substance for a physiologically active compound such as a drug.

[0002]

BACKGROUND OF THE INVENTION Optically active sulfonamide compounds are important compounds used as synthetic raw materials and intermediates for pharmaceuticals. For example, in Japanese Patent Laid-Open No. 10-195038,
Formula (c) having both thromboxane A ₂ antagonism and leukotriene D ₄ antagonism:

[0003]

[Chemical 6]

(In the formula, R ¹ is a straight-chain or branched-chain alkyl group having 4-8 carbon atoms, or a straight-chain or branched-chain group having 4-8 carbon atoms substituted with one or more fluorine atoms. Is an alkyl group, R ² is a hydrogen atom or a lower alkyl group, and R ³ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a nitro group.). Is disclosed. This sulfonamide compound is a compound which is expected to be effective as a platelet aggregation inhibitor, an antithrombotic agent, an antiasthma agent and an antiallergic agent, and is under development. It has been reported that this compound can be produced according to the process represented by the following reaction formula (I) (Japanese Patent Laid-Open No. 2001-2001).
11033). Reaction formula (I):

[0005]

[Chemical 7]

According to this method, the ketone compound represented by the formula (a) is asymmetrically reduced to be converted into the optically active alcohol represented by the formula (f), and the hydroxyl group of the alcohol is substituted to substitute nitrogen. By introducing the group, the target compound represented by the formula (c) can be synthesized. However, in this step, the alcohol compound represented by the formula (f), the trifluoroacetic acid ester compound represented by the formula (g), the azide compound represented by the formula (h), etc. are passed through and the compound represented by the formula (c) is represented. Since a functional group which is not contained in the target substance is introduced and eliminated, the number of steps is increased and the method is not always efficient. Further, there is a problem in safety in using the azide compound represented by the formula (h) and having a risk of explosion.

[0007]

The object of the present invention is to solve the problems in the prior art, to use a safe and simple method with a small number of steps, and enantioselectively with the above formula (c) in a high yield. It is to provide a method for producing the indicated sulfonamide compound.

[0008]

Means for Solving the Problems As a result of intensive studies by the present inventors, as a result of a simple method involving a step of carrying out an asymmetric reduction reaction of a sulfonimide compound, an enantioselective purpose with excellent yield was obtained. It was found that a product was obtained, and the above-mentioned object was achieved.

That is, the present invention provides the following reaction formula (II):

[0010]

[Chemical 8]

As shown in (1), the step (1) of converting the ketone compound represented by the formula (a) into a sulfonimide compound (step 1), and (2) the sulfonimide compound represented by the formula (b) is not generated. A method for producing a sulfonamide compound represented by the formula (c), which comprises a step (step 2) of simultaneous reduction reaction. In the step 2, it is preferable to carry out the asymmetric reduction reaction using a hydride reagent in the presence of an optically active cobalt complex catalyst.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The method for producing the sulfonamide compound of the present invention (hereinafter referred to as "the method of the present invention") will be described in detail below. [Step 1: Reaction of Sulfonyliminating Ketone Compound] Formula (a):

[0013]

[Chemical 9]

From the ketone compound represented by the formula (b):

[0015]

[Chemical 10]

Step 1 for producing the sulfonimide compound represented by can be carried out by the following existing methods (method 1) to (method 3). (Method 1) A ketone compound represented by the formula (a) is reacted with hydroxyamine or a salt thereof in a solvent in the presence of a base to give a compound of the formula (k):

[0017]

[Chemical 11]

An oxime compound represented by the formula (1):

[0019]

[Chemical 12]

A benzenesulfinyl chloride compound represented by: or a compound of formula (m):

[0021]

[Chemical 13]

A method for obtaining a sulfonimide compound represented by the formula (b) by reacting with a benzenesulfonyl cyanide compound represented by (Dale L. Bage)
r, J. Org. Chem. 1992, 57, 4
777. ). (Method 2) By reacting a ketone compound represented by the formula (a) with a hexamethyldisilazane lithium salt previously treated with n-butyllithium in a solvent,
Formula (n):

[0023]

[Chemical 14]

A trimethylsilylimine compound represented by formula (j) is produced, and the obtained trimethylsilylimine compound represented by formula (n) is added to a solvent of formula (j):

[0025]

[Chemical 15]

A method for obtaining a sulfonimide compound represented by the formula (b) by reacting with a sulfonyl chloride compound represented by (Gunda I. Georg, J. et al.
Org. Chem. , 1995, 60 (22), 7
366. ). (Method 3) In the presence of tetraethoxysilane in a solvent, a ketone compound represented by the formula (a) is prepared by the formula (o):

[0027]

[Chemical 16]

A method for obtaining a sulfonimide compound represented by the formula (b) by reacting with a benzenesulfonamide compound represented by (Brian E. Lov.
e, Synlett. 1994, 493. ). In formula (a), formula (b), formula (c), formula (k), and formula (n),
R ¹ is a linear or branched alkyl group having 4 to 8 carbon atoms, or 4 carbon atoms substituted with one or more fluorine atoms.
~ 8 represents a straight chain or branched chain alkyl group.

Examples of the linear or branched alkyl group having 4 to 8 carbon atoms include n-butyl group, sec-butyl group, tert-butyl group, n-pentyl group, 1-methylbutyl group and 2- Methylbutyl group, 3-methylbutyl group, 1-ethylbutyl group, n-hexyl group, 2-methylpentyl group, 3-methylpentyl group, 4-methylpentyl group, n-heptyl group, 2-methylhexyl group, 3-methyl Hexyl group, 4-methylhexyl group, 5-methylhexyl group, n-octyl group, 2-methylheptyl group, 3
-Methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, 6-methylheptyl group and the like can be mentioned.

Examples of the linear or branched alkyl group having 4 to 8 carbon atoms in which one or more fluorine atoms are substituted include, for example, 4-fluorobutyl group, 5-fluoropentyl group and 6-fluoro group. Hexyl group, 4,4-difluorobutyl group, 5,5-difluoropentyl group, 6,6-
Difluorohexyl group, 4,4,4-trifluorobutyl group, 5,5,5-trifluoropentyl group, 6,6
6-trifluorohexyl group, 7,7,7-trifluoroheptyl group, 4,4,4-trifluoro-3-methylbutyl group, 5,5,5-trifluoro-4-methylpentyl group, 6,6 , 6-trifluoro-5-methylhexyl group, 3,3,4,4,4-pentafluorobutyl group,
4,4,5,5,5-pentafluoropentyl group, 5,
5,6,6,6-pentafluorohexyl group, 6,6
7,7,7-pentafluoroheptyl group, 3,3,4
4,5,5,5-heptafluoropentyl group, 4,4
5,5,6,6,6-heptafluorohexyl group, 5,
5,6,6,7,7,7-heptafluoroheptyl group,
3,3,4,4,5,5,6,6,6-nonafluorohexyl group, 4,4,5,5,6,6,7,7,7-nonafluoroheptyl group, 3,3,3 4, 4, 5, 5, 6,
6,7,7,7-undecafluoroheptyl group, 3,
3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl group, 4,4,4-trifluoro-3-trifluoromethylbutyl group,

5,5,5-trifluoro-4-trifluoromethylpentyl group, 6,6,6-trifluoro-5
-Trifluoromethylhexyl group, 3,4,4,4-tetrafluoro-3-trifluoromethylbutyl group, 4,
5,5,5-tetrafluoro-4-trifluoromethylpentyl group, 5,6,6,6-tetrafluoro-5-trifluoromethylhexyl group, 3,3,4,5,5,5
-Hexafluoro-4-trifluoromethylpentyl group, 4,4,5,6,6,6-hexafluoro-5-trifluoromethylhexyl group, 3,4,4,5,5,5
-Hexafluoro-3-trifluoromethylpentyl group, 3,3,4,4,5,6,6,6-octafluoro-5-trifluoromethylhexyl group, 5,5,5-trifluoro-4,4 -Bis (trifluoromethyl) pentyl group, 6,6,6-trifluoro-5,5-bis (trifluoromethyl) hexyl group, 4,4,5,5,6
6,6-heptafluoro-3,3-bis (trifluoromethyl) hexyl group and the like can be mentioned.

R ² represents a hydrogen atom or a lower alkyl group. Examples of the lower alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, a tert-butyl group and the like.

R ³ represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy or a nitro group. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

As the lower alkyl group, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-
Examples thereof include a butyl group, a sec-butyl group and a tert-butyl group. The lower alkoxy group includes methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, sec-butoxy group, tert-group.
Examples thereof include butoxy group.

[Step 2: Asymmetric reduction reaction of sulfonimide compound] By reacting the compound represented by the formula (b) obtained in the step 1 with a hydride reagent in the presence of an optically active cobalt complex catalyst, the formula ( c):

[0036]

[Chemical 17]

A sulfonamide compound represented by can be obtained.

As the optically active cobalt complex used as a catalyst, the following general formula (d) disclosed in JP-A-9-151143:

[0039]

[Chemical 18]

An optically active cobalt (II) complex represented by the following is used.

In the general formula (d) representing the optically active cobalt complex, R ⁴ and R ⁵ are different groups, and each is a hydrogen atom, a linear or branched alkyl group, an aryl group or an aromatic heterocyclic group. It is a cyclic group, and these may have a substituent. Examples of the linear or branched alkyl group include a methyl group, an ethyl group, an n-propyl group,
Isopropyl group, n-butyl group, sec-butyl group, t
A typical example is an ert-butyl group.

Typical examples of the aryl group are substituted or unsubstituted aromatic hydrocarbon groups such as phenyl group and naphthyl group. The aromatic heterocyclic group, a furyl group, a thienyl group, a pyridyl group, a pyrrolyl group, an oxazolyl group, an isoxazole group, a thiazolyl group, an isothiazolyl group, an imidazolyl group, a pyrazolyl group, a pyrimidyl group,
Representative examples are a pyridazinyl group, a pyralidinyl group, a quinolyl group, an isoquinolyl group and the like.

Further, two R ^{4 s} or two R ^{5 s} may be bonded to each other to form a ring.
They may be bonded to each other via a group such as — (CH ₂ ) ₄ — to form a ring such as a 6-membered ring.

Further, R ⁶ , R ⁷ and R ⁸ may be the same or different and each is a hydrogen atom, a linear or branched alkyl group, a linear or branched alkenyl group, an aryl group or an aromatic heterocyclic group. It is a ring group, an acyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, or an aralkyloxycarbonyl group, which may have a substituent. As the linear or branched alkyl group,
Typical examples are methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group and tert-butyl group.

Typical linear or branched alkenyl groups are vinyl and 2-propenyl groups. As the aryl group, a substituted or unsubstituted aromatic hydrocarbon group such as a phenyl group and a naphthyl group is typical. As the aromatic heterocyclic group, a furyl group, a thienyl group, a pyridyl group, a pyrrolyl group, an oxazolyl group, an isoxazole group,
Representative examples are substituted or unsubstituted aromatic heterocyclic groups such as thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, pyrimidyl group, pyridazinyl group, pyraridinyl group, quinolyl group and isoquinolyl group.

As the acyl group, an acetyl group, a trifluoroacetyl group, a propionyl group, a butyryl group, an isobutyryl group, a pivaloyl group or another aliphatic acyl group, a benzoyl group, a 3,5-dimethylbenzoyl group, 2,4,6 -Trimethylbenzoyl group, 2,6-dimethoxybenzoyl group, 2,4,6-trimethoxybenzoyl group, 2,6-
Aromatic acyl groups such as diisopropoxybenzoyl group, 1-naphthylcarbonyl group, 2-naphthylcarbonyl group and 9-anthrylcarbonyl group are typical.

Typical examples of the alkoxycarbonyl group include methoxycarbonyl group, ethoxycarbonyl group, n
Examples include -butoxycarbonyl group, n-octyloxycarbonyl group, cyclopentyloxycarbonyl group, cyclohexyloxycarbonyl group, cyclooctyloxycarbonyl group and tert-butoxycarbonyl group.

A typical example of the aryloxycarbonyl group is a phenoxycarbonyl group. Representative examples of the aralkyloxycarbonyl group include a benzyloxycarbonyl group and a phenethyloxycarbonyl group.

R ⁶ and R ⁷ are connected to each other,
R ⁶ and R ⁷ may form a ring together with the carbon atom to which they are bonded. For example, R ⁶ and R ⁷ are linked to each other, - (CH _{2) 4} - or -CH = CH-CH = CH
In the case of-, a cyclohexane ring or a benzene ring is respectively formed, and the ring such as the cyclohexane ring or the benzene ring formed is, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an n-butyl group. Base,
sec-butyl group, alkyl group such as tert-butyl group, phenyl group, may be substituted with one or more substituents selected from aryl groups such as naphthyl group, the benzene ring is condensed, A condensed polycycle such as a naphthalene ring may be formed.

Specific examples of the optically active cobalt (II) complex represented by the above formula (d) include the following formulas (d-1) to (d).
-9) etc. are mentioned.

[0051]

[Chemical 19]

[0052]

[Chemical 20]

[0053]

[Chemical 21]

[0054]

[Chemical formula 22]

[0055]

[Chemical formula 23]

[0056]

[Chemical formula 24]

[0057]

[Chemical 25]

[0058]

[Chemical formula 26]

[0059]

[Chemical 27]

In the method of the present invention, the following formula (e) obtained by deriving from the optically active cobalt (II) complex represented by the above general formula (d):

[0061]

[Chemical 28]

(In the formula, R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are as defined for the general formula (d), and X ⁻ is
Represents an anion pair capable of forming a salt. The optically active cobalt (III) complex represented by the formula (4) is also effective as a catalyst used in the method of the present invention.

In this general formula (e), X^-As
Is F^-, Cl^-, Br^-, I^-, OH^-, CH₃CO₂ ^-, P
-CH₃C₆H_FourSO₃ ^-, CF₃SO₃ ^-, PF₆ ^-, BF_Four ^-,
BPh_Four ^-, SbF₆ ^-, ClO_Four ^-Etc. are typical.

Specific examples of the optically active cobalt (III) complex represented by the above formula (e) include the following formulas (e-1) to (e-1).
The thing etc. which are represented by (e-3) are mentioned.

[0065]

[Chemical 29]

[0066]

[Chemical 30]

[0067]

[Chemical 31]

The amount of the optically active cobalt complex represented by the general formula (d) or (e) used as a catalyst in the method of the present invention is 0.01 to 20 relative to 1 mol of the compound of the formula (b). Mol%, more preferably 0.5 to
It is 10 mol%.

In the method of the present invention, as the hydride reagent, lithium aluminum hydride, lithium aluminum tri (tert-butoxy) hydride, lithium borohydride, borohydride and borohydride disclosed in JP-A-9-151143 are used. Sodium, potassium borohydride,
Calcium borohydride, ammonium borohydride,
Although any metal hydride such as sodium cyanoborohydride can be used, sodium borohydride is preferable from the viewpoint of operability.

The amount of the hydride reagent used may be 1 to 10 times mol, preferably 1 to 2 times mol, relative to 1 mol of the compound of the formula (b). In the method of the present invention, it is preferable to use a halogen compound as an additive because the optical yield is improved.

The halogen compound used as an additive is trifluoromethylbenzene, dichloromethane, chloroform, carbon tetrachloride, chloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane, methyl dichloroacetate, benzyl chloride, benzal chloride, Dibromomethane,
Examples thereof include bromoform, carbon tetrabromide, bromoethane, 1,2-dibromoethane, methyl iodide, diiodomethane, iodoform and carbon tetraiodide. Among them, dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane, bromoform and iodoform are preferable in that the compound represented by the formula (c) can be obtained with high optical yield and high chemical yield. preferable.

When the above halogen compound is used, the amount used is 0.001-2 with respect to 1 mol of the compound of the formula (b).
It is preferably used in an amount of 0 times mol, particularly 0.01 to 10 times mol. In the above halogen compound, a halogen-based solvent such as dichloromethane, chloroform, carbon tetrachloride or the like may be used as the solvent. In the method of the present invention, it is preferable to use an alcohol compound as an additive because the optical yield is improved.

Alcohol compounds are disclosed in JP-A-9-15114.
Methanol, ethanol, n disclosed in JP-A-3
-Propanol, iso-propanol, n-butanol, sec-butanol, tert-butanol, cyclopentanol, cyclohexanol, cycloheptanol or other aliphatic or alicyclic alcohol, phenol,
Aromatic alcohols such as resorcin, polyalcohols such as ethylene glycol and propylene glycol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, propylene glycol monomethyl ether, tetrahydrofurfuryl alcohol, tetrahydropyran-2-methanol, furfuryl alcohol, tetrahydro Any chain or cyclic ether alcohol such as -3-furan-methanol can be used, but in the present invention,
Preferred are methanol, ethanol and tetrahydrofurfuryl alcohol.

The amount used is preferably 0.01 to 100 times mol, particularly 0.1 to 50 times mol, relative to 1 mol of the compound of the formula (b).

In the method of the present invention, the reaction is preferably carried out in the liquid phase. At this time, a solvent may be used if necessary. The solvent used is
Solvents such as aliphatic hydrocarbon solvents, ether solvents, aromatic hydrocarbon solvents, alicyclic hydrocarbon solvents, ester solvents, and halogen solvents disclosed in JP-A-9-151143 are Any of these can be used, but ether solvents such as tetrahydrofuran, aromatic hydrocarbon solvents such as toluene, and ester solvents such as ethyl acetate are preferable.

The reaction temperature is usually preferably -80 to 30 ° C, more preferably -40 to 10 ° C. The reaction pressure can be usually atmospheric pressure, but the reaction may be performed under increased pressure or reduced pressure. The reaction time is usually 1
It is from 0 minutes to 2 hours. For the reaction, samples of the reaction mixture were sequentially taken and subjected to thin layer chromatography (TL
The progress of the reaction can be confirmed by analyzing C) or the like.

The compound of formula (c) obtained by the above reaction can be purified by a combination of known methods such as column chromatography, extraction and recrystallization.

[0078]

EXAMPLES The present invention will now be described in detail with reference to examples, but the present invention is not limited to these examples. In this example, the silica gel chromatography was performed by Merck No. 9385 silica gel was used.

Example 1 Methyl 4- (4-hexanoylphenyl) butyrate (4.7 g, 17 mmol) was added to a reactor.
1.8 g (25 mmol) of hydroxyamine hydrochloride was added, and 20 ml of methanol was added. After 2 g (25 mol) of triethylamine was added dropwise to the reaction solution at room temperature, the mixture was stirred at that temperature for 3 hours. The reaction solution was concentrated under reduced pressure, water was added, and the mixture was extracted with 50 ml of ethyl acetate. The organic layer was dried over sodium sulfate, the sodium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. Silica gel column chromatography
By separating and purifying with (hexane / ethyl acetate = 5/1), 4.4 g (15 mmol) of methyl 4- [4- (1-hydroxyiminohexyl) phenyl] butyrate was obtained.

(Example 2) 2 g of methyl 4- [4- (1-hydroxyiminohexyl) phenyl] butyrate in a reactor
Add (6.9 mmol), replace with nitrogen and carbon tetrachloride 5m
1 was added. Then, 3.8 ml of triethylamine (2
(8 mmol) was added dropwise, and the reaction solution was cooled to 0 ° C. 2.5 g of paratoluenesulfonyl cyanide in the reaction solution
8 ml of a carbon tetrachloride solution of (13.8 mmol) was added dropwise, and the mixture was stirred at that temperature for 1 hour. Then, the temperature was raised to room temperature, and the mixture was stirred at room temperature for 2 hours. Then, 15 ml of water
In addition, extraction was performed with 30 ml of dichloromethane. The organic layer is dried over sodium sulfate, the sodium sulfate is filtered off,
It was concentrated under reduced pressure. The concentrate was separated and purified by silica gel column chromatography (hexane / ethyl acetate = 3/1) to give methyl 4- [4- (1-paratoluenesulfonyliminohexyl) phenyl] butyrate (1.5 g, 3.5 m).
mol) was obtained.

(Example 3) 13 mg (0.35 mmol) of sodium borohydride was placed in the reactor, the atmosphere was replaced with nitrogen, 1 ml of tetrahydrofuran was added, and the mixture was cooled to -10 ° C. Optically active cobalt (II) complex having the configuration of (S, S) represented by formula (d-6) in a separate container 1.3 m
g (0.0023 mmol, 1 mol relative to the substrate)
%), Methyl 4- [4- (1-paratoluenesulfonyliminohexyl) phenyl] butyrate 100 mg (0.2
3 mmol) and nitrogen substitution, methanol 28 μl
(0.7 mmol), 18 μl of chloroform (0.2
3 mmol) and 1 ml of tetrahydrofuran,
A solution was prepared. Take the prepared solution in a syringe and
The mixture was added dropwise to a sodium borohydride / tetrahydrofuran suspension that had been cooled to ° C, and the mixture was stirred at -10 ° C for 10 minutes. Then, add 2 ml of saline, and add 15 ml of ethyl acetate.
It was extracted with. The organic layer was dried over sodium sulfate, the sodium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The concentrated liquid was separated and purified by silica gel column chromatography (hexane / ethyl acetate = 4/1) to obtain 90 mg (0.21 mmol) of methyl 4- [4- (1-paratoluenesulfonylaminohexyl) phenyl] butyrate. . The optical purity of this product was determined to be 43% ee by HPLC analysis.

Columns used for HPLC measurement conditions: CHIRALPAK OD-H φ4.6 mm
X 250 mm (manufactured by Daicel Chemical Industries, Ltd.) Mobile phase: Hexane / 2-propanol = 90/10 Column temperature: 35 ° C Flow rate: 0.8 ml / min Detection wavelength: 220 nm

(Examples 4 to 5) In each example, the formula (d-
The reaction was performed in the same manner as in Example 3 except that the type of the cobalt catalyst represented by 6) was changed to the catalyst shown in Table 1.
In each of the examples, methyl 4- [4- (1-paratoluenesulfonylaminohexyl) phenyl] butyrate was quantitatively obtained. The results of analyzing the optical purity of the obtained product are shown in Table 1.

[0084]

[Table 1]

[0085]

According to the method of the present invention, a sulfonamide compound can be produced enantioselectively from a ketone compound with a small number of steps and a simple method. The sulfonamide compound is useful as a synthetic intermediate for bioactive compounds such as pharmaceuticals and agricultural chemicals.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) C07M 7:00 C07M 7:00 F term (reference) 4G069 AA06 AA08 BA27A BA27B BC67A BC67B BE13A BE13B BE36A BE36B CB02 DA02 FA01 4H006 AA02 AC61 AC81 BA20 BA32 BA46 BA61 BE23 4H039 CA99 CB30

Claims (4)

[Claims] 1. Formula (a): (In the formula, R ¹ is a linear or branched alkyl group having 4 to 8 carbon atoms, or a linear or branched alkyl group having 4 to 8 carbon atoms substituted with one or more fluorine atoms. R ² represents a hydrogen atom or a lower alkyl group), and the ketone compound represented by the formula (b): (In the formula, R ¹ and R ² represent the same groups as in the formula (a). R ³
Represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a nitro group. ), And then asymmetrically reduced to give a sulfonimide compound represented by the formula (c): (In the formula, R ¹ , R ² and R ³ represent the same groups as those in the formulas (a) and (b).) A method for producing an optically active sulfonamide compound. 2. In the step of producing a compound represented by the formula (c), the compound represented by the formula (b) is subjected to asymmetric hydride reduction in the presence of an optically active cobalt complex catalyst and a hydride reagent, ) The method according to claim 1, which comprises converting to an optically active sulfonamide compound represented by the formula (1). 3. The optically active cobalt complex catalyst is one of the following:
General formula (d): [Chemical 4] Or general formula (e): [Chemical 5] (In the general formulas (d) and (e), R^FourAnd R⁵Is different
A hydrogen atom, a straight chain or a branched chain, respectively.
-Like alkyl group, aryl group or aromatic heterocyclic group
And these may have a substituent, two R^Four
Two or two R⁵Each other bonds to each other to form a ring
R may⁶, R⁷And R ⁸Are the same
May be different, and may be a hydrogen atom, straight chain or branched chain
Alkyl group, linear or branched alkenyl group,
Aryl group, aromatic heterocyclic group, acyl group, alkoxy group
Rubonyl group, aryloxycarbonyl group or aral
Is a cycloalkyloxy group, which has a substituent
May be. R⁶And R⁷Are connected to each other by R⁶Over
And R⁷Together with the carbon atom to which
It may be formed and the ring is selected from alkyl and aryl groups.
It may be substituted with at least one group selected from the group consisting of: X
^-Represents an anion pair capable of forming a salt. )
The method according to claim 2, which is a compound. 4. The method according to claim 2, wherein sodium borohydride is used as a hydride reagent in the asymmetric hydride reduction reaction.