JPH03176463A - Pyrrolidinol derivative and its production - Google Patents

Abstract

NEW MATERIAL:A sulfonic acid ester of 4-amino-1-halo-2-butanol expressed by formula I (X is Cl or Br; R is substituted or unsubstituted lower alkyl, phenyl or benzyl) or salt thereof. USE:Useful as an intermediate for synthesizing 3-pyrrolidinol derivative useful as a raw material for medicine, etc. A sulfonic acid ester of 4-holo-3- hydroxybutanenitrile capable of readily preparing is subjected to reduction under acidic conditions and then subjected to cyclization treatment under basic conditions to synthesize the 3-pyrrolidinol derivative. PREPARATION:A sulfonic acid ester of 4-halo-3-hydroxybutanenitrile expressed by formula II is subjected to reduction under acidic conditions to provide the compound expressed by formula I. The above-mentioned reduction is carried out by a catalytic reduction in the presence of a catalyst of Raney nickel, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a 3-pyrrolidinol derivative and a method for producing the same. 3-pyrrolidinol derivatives (hereinafter also referred to as compound (I[) and compound (IID), respectively) represented by - formula (■): and - formula (scream) are compounds useful as raw materials for medicines, etc. - Formula (I): The compound represented by (hereinafter also referred to as compound (1)) is
- It is an important intermediate in producing the compound represented by formula (I[) and circle. The present invention provides a blind method for producing these compounds.

[Prior art and problems to be solved by the invention] Compounds CI) and (Il) produced by the present invention are novel compounds that have not been synthesized to date.Therefore, there is no knowledge regarding their production method. .Compound (2
), for example, a compound where R is methyl is 1,
1,2,4- derived from 2,4-butanetriol
A method of reacting tris(methanesulfonoxy)butane with benzylamine is known (Japanese Patent Application Laid-open No. 63-414
(See Publication No. 52).

However, in this method, the raw material or 2.4-
Butanetriol is expensive and cannot be described as an industrial manufacturing method. The purpose of the present invention is to obtain 3
- To provide compounds useful as pyrrolidinol derivatives and intermediates for their synthesis in a simple and economical manner.

[Means for Solving the Problems] The present inventors have developed a simple and efficient 3-
As a result of intensive studies aimed at establishing an industrial production method for pyrrolidinol derivatives, it was discovered that 3-pyrrolidinol sulfonic ester can be produced by reducing the sulfonic ester of 4-halo-3-hydroxybutanenitrile, which can be easily done manually. , discovered that ■-benzyl-3-pyrrolidinol sulfonic ester can be produced by reacting 3-pyrrolidinol sulfonic ester with benzaldehyde, and that these reactions can be carried out by an industrially advantageous catalytic reduction reaction, The present invention has now been completed.

That is, the present invention is represented by the formula (I): (wherein, 4-Amino-[-halo 2-butanol sulfonic acid ester or salt thereof, -Formula (■): H (wherein R represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or a benzyl group) )
A sulfonic acid ester of 3-pyrrolidinol or a salt thereof, represented by the formula N: (wherein, The sulfonic acid ester of 4-halo 3-hydroxybutanenitrile represented by the formula (I
f): A method for producing a sulfonic acid ester of 3-pyrrolidinol or a salt thereof, which is characterized by converting it into a compound represented by the formula C, in which R is the same as above) - Formula N: (wherein, X is a chlorine atom) or a bromine atom, and R represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or a benzyl group) (hereinafter also referred to as compound N) A sulfone of 4-amino-1-halo-2-butanol, characterized in that it undergoes a reduction reaction under acidic conditions to convert into a compound represented by the general formula (I): (wherein X and R are the same as above) A method for producing an acid ester or a salt thereof, general formula (I): (wherein, 4-
A sulfonic acid ester of amino-l-halo-2-butanol or a salt thereof is cyclized under basic conditions to convert it into a compound represented by the formula (■):■ (wherein R is the same as above) A process for producing a sulfonic acid ester of 3-pyrrolidinol or a salt thereof, and the general formula (■): (wherein R is a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or a benzyl group) )
A sulfonic acid ester of 3-pyrrolidinol or a salt thereof represented by 3-pyrrolidinol or a salt thereof is subjected to a catalytic reduction reaction in the presence of a metal catalyst to convert it into a compound represented by (wherein R is the same as above) The present invention relates to a method for producing a sulfonic acid ester of benzyl-3-pyrrolidinol or a salt thereof.

[Example] In the present invention, there are three types of compounds (1) and (11): racemic form, fR) form, and (S) form. Any of the sulfonic acid esters of halo 3-hydroxybutanenitrile can be synthesized by using the racemic form, the (R) form, and the IS) form, and these are also included in the present invention.

In the present invention, the substituent R is specifically a methyl group, a trifluoromethyl group, an ethyl group, a phenyl group, a p-
Examples include methylphenyl group and benzyl group.

First, a method for producing 4-amino-1-halo-2-butanol sulfonic acid ester (1) and 3-pyrrolidinol sulfonic acid ester (1) will be described.

Regarding the method for producing the sulfonic acid ester N of 4-halo 3-hydroxybutanenitrile, which is the starting material, 4-
It can be obtained by reacting halo-3-hydroxybutanenitrile with a sulfonic acid halide (title of the invention related to the present inventors' invention: "Sulfonic acid ester of 4-halo-3-hydroxybutanenitrile and its production method") Specification (filed on November 1, 1999)
reference).

The reduction of 4-halo 3-hydroxybutanenitrile sulfonic acid ester (2) can also be carried out using a metal hydride, such as lithium aluminum hydride, diborane, aluminum hydride, etc., but as a simpler method,
For example, the reaction may be carried out by a catalytic reduction reaction, and metal catalysts such as Raney metals or alloys, palladium-based catalysts, platinum-based catalysts, rhodium-based catalysts, ruthenium-based catalysts, etc. can be suitably used. More specifically, Raney nickel (Raney Ni), Raney cobalt (Raney Co), Raney copper (Raney
eyCu), platinum oxide (PtOz), o-dium/alumina (Rh/N 203), palladium carbon (P
d/c), rhodium carbon (Rh/C), ruthenium carbon (Ru/C), Raney nickel-chromium (Rane
y N1-Cr), nickel poride (Ni2B), etc., and these can be used alone or as a mixture of two or more. The amount of the catalyst may be 0.1 to 25% (weight %, same hereinafter) based on the sulfonic acid ester N of 4-halo 3-hydroxybutanenitrile. As the solvent, any solvent used in normal catalytic reduction reactions can be used without particular limitation, such as methanol, ethanol, l-propanol, 2-propanol, 1-butanol, water, acetic acid, dioxane, Solvents such as benzene, toluene, hexane, and cyclohexane can be used alone or as a mixture of two or more. The amount of solvent is not particularly limited, but in consideration of reaction efficiency, it may be used 0.5 to 20 times (by weight) the amount of the raw material. The hydrogen pressure is preferably 1 to 50 kg/Cd, particularly 2 to 1
0 kg/cJ is preferred. The reaction temperature is 20-150℃,
Particularly preferred is 20 to 100°C. In addition, the reaction is 1 to 1
It will be held at 00 hours. At this time, the reaction product is mainly a sulfonic acid ester (I) of 4-amino-1-halo-2-butanol, which is a primary amine, or a salt thereof, depending on the catalyst used, reaction temperature, time, and base preparation of the reaction system. In some cases, a cyclized 3-pyrrolidinol sulfonic acid ester (I) or a salt thereof is mainly obtained.

In particular, when the reduction is carried out under acidic conditions, the sulfonic acid ester of 4-amino-1-halo-2-butanol is mainly reduced, and when the reduction is carried out under neutral or basic conditions, it is mainly 3-pyrrolidinol. sulfonic acid esters tend to be converted.

The acids used at this time include hydrochloric acid, sulfuric acid, acetic acid, p-
Toluenesulfonic acid and the like, and bases include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate, or organic bases such as triethylamine, trimethylamine, and pyridine. The amount of acid used is 1. 0 for compound N
．． 1 to 2 equivalents may be used. Moreover, the amount of the base to be used may be 0.1 to 3 equivalents relative to the compound N.

The sulfonic acid ester of 4-amino-1-halo-2-butanol (1) was cyclized with stirring under basic conditions to form 3.
- It can also be a sulfonic acid ester (If) of pyrrolidinol, and if the reduction reaction product is obtained as a mixture of compounds (1) and (II), it can be cyclized in the same manner under basic conditions. This can be used as a sulfonic acid ester of 3-pyrrolidinol. In this cyclization reaction, reaction conditions such as the solvent and base used, reaction temperature, and reaction time may be selected in the same manner as described above.

The reduction reaction can be carried out, for example, by stirring in methanol in the presence of a catalytic amount of Raney cobalt at a hydrogen pressure of 1 to 10 kg/cj at a temperature of 20 to 100°C for 5 to 30 hours. However, 3-pyrrolidinol sulfonic acid ester (1) tends to be obtained as the main product. Alternatively, the reaction may be carried out, for example, in the presence of a catalytic amount of palladium on carbon in methanol under acidic conditions at a hydrogen pressure of 1 to
Under 10kg/cJ, temperature 20-100℃, 5
When done by stirring for ~30 hours, the sulfonic acid ester of 4-amino-l-halo-2-butanol (
1) tends to be obtained as the main product.

The salts of 3-pyrrolidinol sulfonic acid ester (W) and 4-amino-1-halo-2-butanol sulfonic acid ester [1) include hydrochloride, sulfate,
Examples include acetate and p-toluenesulfonate.

Isolation of the product can be easily achieved by distillation, crystallization, or silica gel column chromatography purification after conventional post-treatments such as filtration of the catalyst, but isolation operations do not necessarily need to be limited to these. Therefore, various methods used for ordinary separation and purification can be applied.

Next, a method for producing sulfonic acid ester of l-benzyl-3-pyrrolidinol (Ifl) will be explained.

The raw material 3-pyrrolidinol sulfonic acid ester (
Ii) can be obtained by the method described above, but it can be used in its free form, or its salts such as hydrochloride or sulfate, or these salts can be neutralized with an appropriate base. The mixture of sulfonic acid ester and salt of 3-pyrrolidinol can be used as is. Examples of the base used for neutralization include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate, and organic bases such as triethylamine, trimethylamine, and pyridine. These may be used alone or in a mixture of two or more, and it is particularly preferable to use sodium hydroxide, potassium hydroxide, or a mixture thereof.

In the reaction, first, sulfonic acid ester of 3-pyrrolidinol is mixed in a solvent, preferably cooled to 0 to 10°C, and then benzaldehyde is added.

Here, in order to improve the reaction rate, hydrochloric acid, sulfuric acid, acetic acid,
p-) One or more acids such as luenesulfonic acid and zinc chloride may be added, and one or more dehydrating agents such as anhydrous sodium sulfate, anhydrous magnesium sulfate, and anhydrous potassium carbonate may be added. The amount of acid and dehydrating agent added is 0, OI to 1 relative to the sulfonic acid ester of 3-pyrrolidinol.
Equivalent amounts are preferred.

Next, after adding a metal catalyst, a catalytic reduction reaction is performed to produce a sulfonic acid ester of l-benzyl-3-pyrrolidinol.

The amount of benzaldehyde used is preferably 1 to 3 moles per sulfonic acid ester of 3-pyrrolidinol.

As the metal catalyst, Raney metals or alloys, palladium-based catalysts, platinum-based catalysts, rhodium-based catalysts, ruthenium-based catalysts, etc. can be suitably used.

More specifically, Raney nickel (formerly Raney), Raney cobalt (Raney Co
), Raney Cu, platinum oxide (Pt0
2) , Odium/Alumina (J?h/ /V 20
, palladium carbon (Pd/C), rhodium carbon (
Rh/C), ruthenium carbon (Ru/C), Raney nickel-chromium (Raney N1-Cr), nickel poride (N12B), etc., and these can be used alone or as a mixture of two or more. .

The amount of catalyst used may be 0.1 to 25% based on compound (It). As the solvent, any solvent used in ordinary catalytic reduction reactions can be used without any particular restrictions, such as methanol, ethanol, 1-propanol, 2-propanol, etc.
-Solvents such as propatool, 1-butanol, water, acetic acid, dioxane, benzene, toluene, hexane, and cyclohexane can be used alone or as a mixture of two or more.

The amount of solvent is not particularly limited, but in consideration of reaction efficiency, it may be used 0.5 to 20 times (by weight) the amount of compound (II).

The catalytic reduction reaction is carried out in the presence of a metal catalyst, preferably under a hydrogen pressure of 1 to 10 kg/cj, preferably at a temperature of 20 to 10 kg/cj.
0°C, particularly preferably 20-50°C, preferably 1-50°C
This can be carried out by stirring for 100 hours, particularly preferably for 1 to 50 hours.

At this time, the reaction product depends on the catalyst species used, the presence or absence of addition of acid, etc., and the base preparation of the 3-pyrrolidinol sulfonic acid ester used as the substrate.
- Obtained as a sulfonic acid ester of pyrrolidinol or a salt thereof, or a mixture thereof.

Examples of the salt of sulfonic acid ester (III) of 1-benzyl-3-pyrrolidinol include hydrochloride, sulfate, acetate,
Examples include p-toluenesulfonate.

Isolation of the product can be easily achieved by distillation, crystallization, or silica gel column chromatography purification after conventional post-treatments such as filtration of the catalyst, but the isolation procedure is not necessarily limited to these methods. There is no need to limit it, and various methods commonly used for separation and purification can be applied.

Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited only to the Examples.

Reference Example 1 (Synthesis of 4-chloro-3-p-toluenesulfonyloxybutanenitrile) 10.0 g of 4-chloro-3-hydroxybutanenitrile
24 ml of 1-pyridine was dissolved in 40 ml of methylene chloride, and 28.7 g of p-toluenesulfonyl chloride was added under water cooling. After stirring at room temperature for 21 hours, 1 ml of water was added under water cooling, and the mixture was stirred for 1 hour. After adding methylene chloride to the reaction solution and separating the aqueous layer, the organic layer was washed with a saturated aqueous copper sulfate solution, water, saturated aqueous sodium bicarbonate, and saturated brine, dried, filtered, and concentrated under reduced pressure to obtain 22.7 g of a crude product. I got it. This was purified by silica gel column chromatography (200 g of silica gel, hexane: ethyl acetate - 85:15 (volume ratio, same below))
18.7 g of the target product was obtained (yield: 82%).

Example 1 (Synthesis of 4-chloro-ap-toluenesulfonyloxybutylamine) 3.00 g of 4-chloro-3-p-toluenesulfonyloxybutanenitrile obtained in Reference Example 1 was dissolved in methanol 3
1.5 f of 5% palladium on carbon powder and 1.15 ml of concentrated hydrochloric acid were added, and the mixture was stirred at 50°C for 15 hours under a hydrogen pressure of 7 kg/cJ. After filtering the reaction solution,
Concentrate solution a to obtain 3,7 containing mainly 4-chloro-3-p toluenesulfonyloxybutylamine hydrochloride.
g of crude product was obtained. This was purified by silica gel column chromatography (30 g of silica gel, acetone) to obtain 2.0 g of 4-chloro-3-p-)luenesulfonyloxybutylamine hydrochloride (yield 58%).

Rr value and 'II- of the obtained compound in TLC
The NMR DJ determination results are shown below.

R1' value: 0.6 (Developing solvent l-butanol: ethyl acetate: acetic acid: water-1: 1: 1: 1)'ll-
NMR (90 MIIz, CD (J3 + D20
) δppm (internal standard TMS): 1.76-2.50 (11,2H), 2.29 (s, 3
H), 2.61-3.15 (m, 211), 3.27 (
d, J-51z, 2H), 5.22(br,,lH),
7.10 (d, J-8Jlz, 211) 7.71 (d
, JJIIz, 211).

Reference Example 2 (Synthesis of benzamide of 4-chloro-3-p-toluenesulfonyloxybutylamine) 219 mg of 4-chloro-a-p-)luenesulfonyloxybutylamine hydrochloride obtained in Example 1 was added to 2 ml of pyridine. Dissolve and cool with water, benzoyl chloride 0,2
3 ml was added dropwise. After stirring for 2.5 hours under water cooling,
Water was added to the reaction solution and stirred for 30 minutes. The reaction solution was mixed with water.
Pour into ether, separate the ether layer, wash the organic layer with saturated copper sulfate, aqueous solution, water, saturated aqueous sodium bicarbonate, and saturated brine,
Drying, filtration, and concentration under reduced pressure gave a crude product. this,
Purified by silica gel column chromatography (silica gel 30 g 1 hexane:ethyl acetate - 3:1) to 188
mg of 4-chloro-a-p-)luenesulfonyloxybutylamine benzamide was obtained (yield 83%).

Rr value of the obtained compound in TLC, 1:2 cm
' and 1H-NMR measurement results are shown below.

Rr value: 0.4 (developing solvent hexane: ethyl acetate)
1:1) 1370, 1200, 1190, 950'II-NMR
(90MIIz, CD(J3)δppm (internal standard TMS): 1.73-2.29 (a, 2H), 2.3
9 (S, 3H), 3.06-3.89 (m, 211),
3.48 (d, J-511z, 211), 4.67-5
．． 00 (m, IH), 6.76-7.15 (m, LH)
, 7.20-7.80 (m, 5H), 7.67-8.0
0 (m, 4H).

From the above results, it was confirmed that the substance obtained in Example 1 was 4-chloro-ap-toluenesulfonyloxybutylamine.

Example 2 (Synthesis of 3-p-toluenesulfonyloxypyrrolidine) 3.00 g of 4-chloro-3-p-toluenesulfonyloxybutanenitrile obtained in Reference Example 1 was mixed with methanol 1
Dissolve in 5ml, add 330■ of Raney cobalt, 7
Stirred at 60 °C for 12 h under hydrogen pressure of kg/cj. After filtering the reaction solution, the filtrate is concentrated to mainly contain 3-p.
-) 3.1 g of crude product containing luenesulfonyloxypyrrolidine hydrochloride was obtained. This was purified by silica gel column chromatography (30 g of silica gel, 1 acetone:ethanol - 4:1 to 1:1) to give a concentration of 1.50
g of ap-toluenesulfonyloxypyrrolidine hydrochloride was obtained (yield 49%).

Rr value and '+1− of the obtained compound in TLC
The NMR measurement results are shown below.

Rr value: 0.7 (Developing solvent l-butanol: ethyl acetate: acetic acid: water 1; 1: 1: 1) 'II-
NMR (90MHz, CDC#s) δppa+
(Internal standard TMS): 1.89-2.77 (Im, 2H), 2.40 (s,
3H), 3.06-3.80 (m, 4H), 5.14 (
br, s, IH), 7.33 (d; J=8Hz, 211
), 7.77 (d, J-8Hz.

211), 8.7-10.8 (br,, 2H).

Example 3 (Synthesis of l-benzyl-3-p-toluenesulfonyloxypyrrolidine) -3-p-)luenesulfonyloxypyrrolidine hydrochloride obtained in Example 2 600 μ, benzaldehyde 600
Dissolve ■ in 10ml of methanol and 15ml of Raney nickel.
After adding 0 ■, 20% NaOH in methanol solution 0.1
ml was added to adjust the pH to 7.5.

After stirring for 12 hours at 30° C. under a hydrogen pressure of 2 kg/cj, the reaction solution was filtered and the filtrate was concentrated, yielding 17 g of crude product. This was purified by silica gel column chromatography (30 g of silica gel, hexane:ethyl acetate - 3:1) to give 575 μl of 1-benzyl-3-p-
Toluenesulfonyloxypyrrolidine was obtained (yield 80
%).

The measurement results of Elareta Compound (7) ν""-"H-NMR and IIax (") and elemental analysis are shown below.

, neat ctll-1: 1600.1500.
1460.1370.1180゜aX 00 1H-NMR (90MHz, CDCl5) δppm (
Internal standard TMS): 1.66-2.38 (m, 2H)
, 2.32 (s, 3H), 2.52-2.89 (m, 4
H), 3.57 (S, 2H)', 4.98 (m, LH)
, 7.28 (s, 5H), 7.18-7.48 (d, 2
H), 7.80 (d, J-8Hz, 2H) elemental analysis value:
(as Cl8 H2+ N 038) Calculated value (%
): C85,23H8,39N 4.23 Measured value (%): C65,3511[i,2ON
4.01 From the above results, the substance obtained in Example 2 is 3-p
- It was confirmed that it was toluenesulfonyloxypyrrolidine.

Example 4 (Synthesis of 3-p-toluenesulfonyloxypyrrolidine) 500 mg of 4-chloro-3-p-toluenesulfonyloxybutylamine hydrochloride (1,34
Dissolve wmol) in 5 ml of methanol and add 20% Na
Add 0.4ml of methanol solution of 011 and incubate at 25℃ for 2 hours.
Stirred for 4 hours. After adding 0.35 ml of 6N hydrochloric acid aqueous solution under water cooling, the reaction solution was concentrated, and the resulting crude product was purified by silica gel column chromatography (silica gel Lo
g, acetone:ethanol-4:1 to 1:1) to obtain 3-p-toluenesulfonyloxypyrrolidine hydrochloride 264B (yield 71%).

Rf' value in TLC of the obtained compound and 1H
-NMR measurement results were the same as in Example 2.

Reference Example 3 (Synthesis of I-benzyl-3-butanoyloxypyrrolidine) 460 μl of l-benzyl-ap-toluenesulfonyloxypyrrolidine obtained in Example 3 and 180 μg of sodium butyrate were dissolved in 1.2 g of acetic acid. , and reacted at 100°C for 12 hours. Methylene chloride was added to the reaction solution, washed with saturated aqueous sodium bicarbonate and saturated brine, dried, filtered, and concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (silica gel 30 g 1 hexane: ethyl acetate-1
:2) to obtain 240 μ of 1-benzyl-3-butanoyloxypyrrolidine (yield 70%).

[Effects of the Invention] According to the present invention, 3-pyrrolidinol derivatives useful as raw materials for pharmaceuticals can be easily, economically and efficiently produced using easily prepared sulfonic acid ester of 4-halo-3-hydroxybutanenitrile. You can wander around the target.

Claims (1)

[Claims] 1. General formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X is a chlorine atom or a bromine atom, and R is a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group or benzyl group) or a salt thereof. 2. The compound according to claim 1, wherein X is a chlorine atom. 3 General formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) (In the formula, R represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or a benzyl group)
A 3-pyrrolidinol sulfonic acid ester or a salt thereof. 4 R is a methyl group, a trifluoromethyl group, an ethyl group,
4. The compound according to claim 1, 2 or 3, which is a phenyl group, p-methylphenyl group or benzyl group. 4. The compound according to claim 1, 2 or 3, wherein 5R is a methyl group or a p-methylphenyl group. 6 General formula (IV): ▲Mathematical formulas, chemical formulas, tables, etc.▼(IV) (In the formula, X is a chlorine atom or a bromine atom, and R is a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or A sulfonic acid ester of 4-halo-3-hydroxybutanenitrile represented by a benzyl group is subjected to a reduction reaction to produce the general formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R 3-pyrrolidinol is the same as above). 7 General formula (IV): ▲Mathematical formulas, chemical formulas, tables, etc.▼(IV) (In the formula, X is a chlorine atom or a bromine atom, and R is a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or The sulfonic acid ester of 4-halo-3-hydroxybutanenitrile represented by (representing a benzyl group) is subjected to a reduction reaction under acidic conditions, and the general formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) ( 4-amino-1-halo-2-, which is converted into a compound represented by the formula (wherein X and R are the same as above)
A method for producing butanol sulfonic acid ester or its salt. 8. The method according to claim 6 or 7, wherein the reduction reaction is carried out using a catalytic reduction reaction in the presence of a metal catalyst. 9. Claim 6 or 7, wherein the reduction reaction is carried out using a catalytic reduction reaction in the presence of at least one selected from the group consisting of a Raney catalyst, a platinum-based catalyst, a rhodium-based catalyst, a ruthenium-based catalyst, and a palladium-based catalyst. Manufacturing method described. 10. The method according to claim 6, wherein the reduction reaction is carried out using a catalytic reduction reaction in the presence of Raney nickel or Raney cobalt. 11 General formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X is a chlorine atom or a bromine atom, and R is a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or A sulfonic acid ester of 4-amino-1-halo-2-butanol or a salt thereof represented by the formula (representing a benzyl group) is cyclized under basic conditions to form the general formula (
II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) A method for producing a sulfonic acid ester of 3-pyrrolidinol or its salt, which is characterized by converting it into a compound represented by (in the formula, R is the same as above) . 12. Claim 6, 7, 8, 9, 10 or 1, wherein X is a chlorine atom and R is a methyl group or p-methylphenyl group.
The manufacturing method described in 1. 13 General formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) (In the formula, R represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted phenyl group, or a benzyl group)
A sulfonic acid ester of 3-pyrrolidinol or its salt represented by 3-pyrrolidinol or its salt is subjected to a catalytic reduction reaction in the presence of a metal catalyst to produce the general formula (III): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) is the same as above). 14. Claim 13: The metal catalyst is at least one selected from the group consisting of Raney catalyst, platinum oxide, rhodium catalyst, ruthenium catalyst, and palladium catalyst.
Manufacturing method described. 15. The method according to claim 13, wherein at least one selected from the group consisting of Raney cobalt, Raney nickel, and Raney copper is used as the metal catalyst. 16. The method according to claim 13, 14 or 15, wherein 16R is a methyl group or a p-methylphenyl group.