JP2022034093A - Method of producing alkane iodide derivative - Google Patents

Abstract

To provide a method of producing an alkane iodide derivative capable of producing an alkane iodide derivative even in a nonpolar solvent.SOLUTION: The method of producing an alkane iodide derivative includes: contacting an alkane derivative represented by the following formula (1) where, in the formula, R1-R3 are an alkyl group, an aralkyl group, or a hydrogen atom, and X is a group selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, a mesyloxy group, and a tosyloxy group, with an alkali metal iodide salt in an organic solvent in the presence of 4 substituted ammonium halide to produce an alkane iodide derivative substituted with iodine for X of the above formula (1).SELECTED DRAWING: None

Description

The present invention relates to a novel method for producing an alkane iodide derivative. More specifically, the present invention relates to a novel method for producing an alkane iodide derivative capable of producing an alkane iodide derivative even in a non-polar solvent.

The alkane iodide derivative is an extremely useful compound as a raw material for synthesizing various bioactive compounds including pharmaceuticals (Non-Patent Document 1). As the main synthetic method, a method of contacting an alkali metal iodide salt with an alkane derivative having a leaving group (leaving group: chlorine, bromine, tosiloxy group, mesiloxy group) is known as a Finkelstein reaction. This reaction utilizes the difference in solubility of halogenated alkali metal salts in polar solvents such as acetone. For example, NaI is soluble in acetone, but NaBr is practically insoluble in acetone. From this, the equilibrium shifts in the direction in which RI is produced, and the halogen exchange reaction from bromide (R-Br) to iodide (RI) proceeds.

The Finkelstein reaction has been widely used as a general synthetic method for alkane iodide derivatives, including large-scale industrial production methods.

However, in order to realize the difference in solubility of the above-mentioned halide alkali metal salts, the reaction solvent is limited to polar solvents such as acetone and 2-butanone (Non-Patent Documents 2 and 3), and in non-polar solvents. It was impossible in principle to carry out this reaction. Therefore, when the obtained alkane iodide derivative is used in the next step or reaction, it may not be usable unless it is replaced with a solvent or the alkane iodide derivative is isolated.

Journal of The American Chemical Society 2002, 124, 12424-12425 Journal of The American Chemical Society 20011, 123, 11586-11593 The Journal Organic Chemistry 2002, 67, 746-771

Therefore, an object of the present invention is to provide a method for producing an alkane iodide derivative capable of producing an alkane iodide derivative even in a non-polar solvent.

The present inventors have made extensive studies to solve the above problems. As a result, they have found that an alkane derivative having a leaving group can be contacted with an alkali metal iodide salt in the presence of a tetra-substituted ammonium salt to produce an alkane iodide derivative even in a non-polar solvent. The invention was completed.

That is, the present invention has the following equation (1).

(In the formula, R ¹ to R ³ may contain at least one group selected from a halogen atom, an ester group, a carboxyl group, an amide group, a nitrile group, a nitro group, an aldehyde group and a ketone group, and may contain an alkyl group. Alternatively, it is an aralkyl group or a hydrogen atom, and ^R1 to R3 may be the same group or different groups ^, respectively ^, and ^R1 to R3 may be an alkyl group or an aralkyl group. , May be bonded to each other to form a ring. X is a group selected from a fluorine atom, a chlorine atom, a bromine atom, a mesiloxy group or a tosiloxy group.)
The alkane derivative represented by
In an organic solvent,
Expressed by the following equation (2)

(In the formula, R ⁴ to R ⁷ are alkyl groups or aralkyl groups, which may be the same group or different groups, respectively. X is a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. , A hydroxyl group, or a hydrogen sulfate group.)
In the presence of a tetra-substituted ammonium salt
React by contacting with alkali metal iodide,
The following formula (3)

(In the formula, R ¹ to R ³ have the same meaning as those in the above formula (1).)
It is a method for producing an alkane iodide derivative, which produces an alkane iodide derivative represented by.

In the present invention, the organic solvent is preferably a non-polar solvent. Further, it is preferable to bring it into contact with an alkali metal iodide salt in the presence of water.

According to the method for producing an alkane iodide derivative of the present invention, an alkane derivative having a leaving group is brought into contact with an alkali metal iodide salt in the presence of a tetra-substituted ammonium salt, so that a non-polar solvent can be used as the solvent. Alkane iodide derivatives can be produced. In the conventional method, an alkane iodide derivative could not be obtained when a non-polar solvent was used as the solvent.

According to the method for producing an alkane iodide derivative of the present invention, an alkane iodide derivative can be obtained even if a non-polar solvent is used. Therefore, it is necessary to replace the solvent or isolate the alkane iodide derivative in order to use it so far. It can be used in the same steps and reactions without these operations, and is an extremely useful method for producing synthetic materials for various physiologically active compounds including pharmaceuticals, and the industrial utility value of the present invention is high. Very expensive.

The present invention is a method for producing an alkane iodide derivative, which comprises contacting the alkane derivative with an alkali metal iodide salt in the presence of a tetra-substituted ammonium salt in an organic solvent to produce the alkane iodide derivative. Hereinafter, the present invention will be described in detail.

(Alkane derivative)
In the present invention, the alkane derivative is represented by the following formula (1).

It is a compound represented by.

In the formula (1), R ¹ to R ³ are a halogen atom, an ester group (-COO-), a carboxyl group (-COOH), an amide group (-CONH-), a nitrile group (-CN), and a nitro group (-CN). -NO ₂ ), an alkyl group or an aralkyl group or a hydrogen atom which may contain at least one group selected from an aldehyde group (-CHO) and a ketone group (-CO-). R ¹ to R ³ may be the same group or different groups, respectively. Further, when at least two of R ¹ to R ³ are an alkyl group or an aralkyl group, they may be bonded to each other to form a ring.

The alkyl group preferably has 1 to 20 carbon atoms, and the aralkyl group preferably has 7 to 20 carbon atoms. The halogen atom, ester group, carboxyl group, amide group, nitrile group, nitro group, aldehyde group and ketone group may be substituted anywhere in the alkyl group or the aralkyl group. When the ester group, amide group and ketone group are substituted on the aromatic ring of the aralkyl group, the group attached to the other bond of these groups is not particularly limited, but an alkyl group or an aralkyl group is preferable. When the alkyl group or aralkyl group having R ¹ to R ³ has the above-mentioned group, the carbon number thereof also includes the carbon number of the above-mentioned group.

X is a group selected from a fluorine atom, a chlorine atom, a bromine atom, a mesiloxy group (-OMs) or a tosiloxy group (-OTs).

The alkane derivative represented by the formula (1) is the following formula (1A).

(In the formula, R is an alkyl group having 1 to 6 carbon atoms or an aralkyl group having 7 to 11 carbon atoms, and X is a chlorine atom or a bromine atom.)
In the case of 5-halogenovaleric acid ester represented by, the following formula (3A) useful for introducing a side chain into an intermediate for biotin synthesis by the method of the present invention.

(In the formula, R is synonymous with that in the above formula (1A).)
5-Iodine valeric acid ester represented by can be produced.

In the formula (1A), R is an alkyl group having 1 to 6 carbon atoms or an aralkyl group having 7 to 11 carbon atoms, and is preferably an alkyl group having 1 to 4 carbon atoms.

As the alkane derivative represented by the formula (1), a compound represented by the following chemical formula can be mentioned as preferable.

(Organic solvent)
In the present invention, an alkane derivative represented by the formula (1) is produced in an organic solvent. The organic solvent is not particularly limited as long as it does not inhibit the reaction, but a low-polarity or non-polar organic solvent is preferable.

Examples of the organic solvent include esters such as ethyl acetate, methyl acetate, butyl acetate and isopropyl acetate, nitriles such as acetonitrile and propionitrile, hydrocarbons (THF), 2-methyl THF, 1,4-dioxane and tert-butyl. Ethers such as methyl ether, cyclopentylmethyl ether, dimethoxyethane, diglyme, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, aromatic hydrocarbons such as toluene and xylene. , Hexane, and aliphatic hydrocarbons such as heptane can be mentioned. Preferred are non-polar solvents such as ethyl acetate, butyl acetate, THF, 2-methyl THF, 1,4-dioxane, tert-butylmethyl ether, dimethoxyethane, chloroform, chlorobenzene, toluene and xylene. These organic solvents can be used alone or as a mixed solvent thereof.

The amount of the organic solvent used is not particularly limited. It is preferable to use 1 to 100 times the volume of the organic solvent, and more preferably 2 to 10 times the volume of the alkane derivative represented by the formula (1). When a mixed solvent is used as the reaction solvent, the total amount of the mixed solvent may satisfy the above range.

(4-substituted ammonium salt)
In the present invention, the tetra-substituted ammonium salt is represented by the following formula (2).

It is a compound represented by. When the tetra-substituted ammonium salt is not present in the reaction system, the reaction does not proceed or is slow, and the desired alkane iodide derivative represented by the formula (3) cannot be efficiently produced.

In the formula (2), ^R4 to ^R7 are alkyl groups or aralkyl groups, and may be the same group or different groups, respectively. Further, it is preferable that at least three of R ⁴ to R ⁷ are alkyl groups.

The alkyl group preferably has 1 to 20 carbon atoms, and more preferably 1 to 4 carbon atoms. The aralkyl group preferably has 7 to 20 carbon atoms, and more preferably 7 to 10 carbon atoms.

X is a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, or a hydrogen sulfate group, and is preferably a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, or a hydrogen sulfate group.

Examples of the tetra-substituted ammonium salt represented by the formula (2) include tetra-n-butylammonium iodide (TBAI), tetramethylammonium iodide (TMAI), tetra-n-butylammonium bromide (TBAB), and tetra-n-. Butylammonium chloride (TBAC), Tetramethylammonium chloride (TMAC), Tetra-n-butylammonium fluoride (TBAF), Tetra-n-butylammonium hydrogen sulfate, benzyltrimethylammonium iodide, benzyltrimethylammonium bromide, benzyltrimethyl Preferred examples include ammonium chloride, benzyltrimethylammonium fluoride, benzyltrimethylammonium hydrogen sulfate, tetraethylammonium iodide, tetraethylammonium bromide, tetraethylammonium chloride, tetraethylammonium fluoride, and tetraethylammonium hydrogen sulfate.

The amount of the tetra-substituted ammonium salt represented by the formula (2) is not particularly limited. It is preferable to use 0.001 to 1 mol, and more preferably 0.005 to 0.1 mol, with respect to 1 mol of the alkane derivative represented by the formula (1).

(Alkali metal iodide)
In the present invention, the alkali metal iodide salt is not particularly limited, but it is preferable to use sodium iodide from the viewpoint of reactivity with the tetrasubstituted ammonium salt and the price.

The amount of the alkali metal iodide used is not particularly limited. It is preferable to use 1 to 5 mol, and more preferably 1 to 2 mol, with respect to 1 mol of the alkane derivative represented by the formula (1).

(water)
In the present invention, it is preferable that water is present in the reaction system because the reaction rate is improved. The water is not particularly limited, and tap water, ion-exchanged water, distilled water and the like can be used. The amount of water used is not particularly limited, and it is preferable to use 0.001 to 1 times the volume of the organic solvent, and more preferably 0.005 to 0.1 times the volume. By setting the amount of water used in this range, the reaction rate is improved, and the target alkane iodide derivative represented by the formula (3) can be produced in a shorter time.

(Manufacturing of alkane iodide derivative)
In the present invention, an alkane derivative is reacted by contacting it with an alkali metal iodide salt in the presence of a tetra-substituted ammonium salt in an organic solvent to produce an alkane iodide derivative. The reaction can be carried out by mixing each component.

The method of mixing each component is not particularly limited, and can be carried out in a reaction vessel equipped with a stirrer. The procedure for adding each component into the reaction vessel is represented by the formula (1) in which the alkali derivative represented by the formula (1), the tetrasubstituted ammonium salt represented by the formula (2) and the organic solvent are previously charged in the reaction vessel. A method is preferable in which the alkane derivative and the tetrasubstituted ammonium salt represented by the formula (2) are dissolved in an organic solvent, and then the alkali metal iodide salt and, if necessary, water are added and mixed while stirring.

The order in which the alkane derivative represented by the formula (1), the tetrasubstituted ammonium salt represented by the formula (2) and the organic solvent are charged into the reaction vessel is not particularly limited, but the organic solvent is first charged and then the formula (1) is stirred. It is preferable to add and dissolve the alkane derivative represented by the above in this order and the tetrasubstituted ammonium salt represented by the formula (2) in this order. The temperature at the time of this addition and dissolution is not particularly limited, and can be carried out in the range of 5 ° C to 200 ° C. More specifically, the temperature is preferably 20 ° C to 150 ° C, more preferably 30 ° C to 120 ° C.

The temperature at the time of adding the alkali metal iodide salt is not particularly limited and may be the same as the above temperature range. After adding the alkali metal iodide salt, the temperature is set to 10 ° C to 200 ° C and the reaction is carried out. More specifically, the temperature is preferably 30 ° C to 140 ° C, more preferably 40 ° C to 120 ° C. By carrying out the reaction in the temperature range, the reaction can proceed in a high yield and in a short time.

The reaction time is not particularly limited, and may be appropriately determined while confirming the conversion rate to the alkane iodide derivative represented by the product formula (3), but is usually 0.5 hours or more 72. It may be less than an hour, preferably 0.5 hours or more and 60 hours or less, and more preferably 1 hour or more and 50 hours or less. If water is also added when the alkali metal iodide salt is added, the reaction rate is improved, and the desired alkane iodide derivative represented by the formula (3) can be produced in a shorter time. In that case, the reaction time is usually 0.5 hours or more and 24 hours or less, preferably 1 hour or more and 10 hours or less, and more preferably 1 hour or more and 4 hours or less.

The reaction atmosphere is also not particularly limited, but is preferably under an inert gas atmosphere and an air atmosphere.

Further, the inside of the reaction system may be under atmospheric pressure, pressurized pressure, or reduced pressure. Above all, it is preferable to carry out under atmospheric pressure.

In the present invention, the following formula (3) is obtained by the above reaction.

The alkane iodide derivative represented by is obtained. In the formula (3), R ¹ to R ³ have the same meaning as those in the formula (1).

The obtained alkane iodide derivative represented by the formula (3) can be separated by the following method. For example, the reaction solution may be washed with an aqueous solution of sodium thiosulfate and water, and the organic layer may be concentrated under reduced pressure.

Further, the obtained alkane iodide derivative represented by the formula (3) can be further purified by a known method such as column separation and recrystallization.

The obtained alkane iodide derivative represented by the formula (3) can be suitably used as a synthetic material for various bioactive compounds including pharmaceuticals.

For example, the alkane iodide derivative represented by the formula (3) is represented by the following formula (3A).

(In the formula, R is synonymous with that in the above formula (1A).)
In the case of 5-iodovaleric acid ester represented by, it can be used in the reaction of introducing a side chain into an intermediate of biotin synthesis.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto, but is a specific example.

(Measurement and quantification of conversion rate of 5-iodoethyl pentanoate)
The conversion rate of ethyl 5-bromoethyl pentanoate (hereinafter, also referred to as Br-TAI) to ethyl 5-iodoethyl pentanoate (hereinafter, also referred to as I-TAI) and the quantification of I-TAI are as follows by gas chromatography. I went under the conditions of.

Gas Chromatography Analytical Condition Equipment: Agilent Technologies 7820A GC System
Column: HP-5 manufactured by Agilent Technologies (30m x 0.32mm x 0.25μm)
Column temperature: 100-280 ° C 10 ° C / min
Sample introduction temperature: 300 ° C
Detector temperature: 300 ° C
Carrier gas: He, 1.1 mL / min, split 1:60
Detector: Hydrogen flame ionization detector (FID)
Introduced amount: 0.2 μL.

Example 1
The reaction represented by the following formula was carried out to produce an alkane iodide derivative.

Br-TAI (10.0 g, 47.8 mmol) and tetra-n-butylammonium iodide (TBAI, 1.06 g, 2.87 mmol) were dissolved in toluene (50 mL) in a reaction vessel and then at 25 ° C. Sodium iodide (8.6 g, 57.4 mmol) and distilled water (500 μL) were added, and the mixture was stirred at 100 ° C. for 2 hours.

After cooling the reaction solution to room temperature, a part of the reaction solution was taken, dissolved in chloroform, 10% hydrochloric acid was added to separate the layers, and the obtained organic layer was analyzed by gas chromatography. As a result, Br-TAI was transferred to I-TAI. The conversion rate was 99.43%.

The reaction solution was washed with 10% aqueous sodium thiosulfate solution (20 mL) and water (20 mL), and then the organic layer was concentrated under reduced pressure to obtain I-TAI (12.1 g, Br-TAI as a reference). Yield: 99%).

The results of ¹ H-NMR measurement of the obtained I-TAI are shown.
¹ H-NMR (400MHz, CDCl ₃ ) δ: 4.11 (I (CH ₂ ) ₄ CO ₂ CH ₂ CH ₃ , q, J = 7.2Hz) 3.19 (I CH ₂ (CH ₂ ) ₃ CO ₂ Et, t, J = 7.0 Hz) 2.33 (I (CH ₂ ) ₃ CH ₂ CO ₂ Et, t, J = 7.4 Hz) 1.86 (ICH ₂ CH ₂ (CH ₂ )) ₂ CO ₂ Et, m), 1.74 (I (CH ₂ ) ₂ CH ₂ CH ₂ CO ₂ Et, m), 1.26 (I (CH ₂ ) ₂ CO ₂ CH ₂ CH ₃ , t, J = 7.2Hz).

Example 2
After dissolving Br-TAI (1.0 g, 4.78 mmol) and tetra-n-butylammonium iodide (TBAI, 105.9 mg, 0.287 mmol) in toluene (5.0 mL) in a reaction vessel, 25 Sodium iodide (860.1 mg, 5.74 mmol) was added at ° C, and the mixture was stirred at the same temperature for 67 hours. Since the conversion from Br-TAI to I-TAI did not proceed, the temperature was then raised to 100 ° C. and the mixture was stirred for 40 hours.

A part of the reaction solution was taken, dissolved in chloroform, 10% hydrochloric acid was added to separate the solutions, and the obtained organic layer was analyzed by gas chromatography. As a result, the conversion rate of Br-TAI to I-TAI was 93. It was 99%.

Comparative Example 1
Br-TAI (1.0 g, 4.78 mmol) was dissolved in toluene (10 mL), sodium iodide (860.1 mg, 5.74 mmol) was added at 25 ° C., and the mixture was stirred at the same temperature for 67 hours. Then, the temperature was raised to 100 ° C. and the mixture was stirred for 24 hours, but the reaction did not proceed at all.

Example 3
The reaction represented by the following formula was carried out to produce I-TAI from Br-TAI, and the side chain was introduced into a biotin intermediate using the I-TAI.

Br-TAI (10.0 g, 47.8 mmol) and tetra-n-butylammonium iodide (TBAI, 1.06 g, 2.87 mmol) were dissolved in toluene (50 mL) in a reaction vessel and then at 25 ° C. Sodium iodide (8.6 g, 57.4 mmol) and distilled water (500 μL) were added, and the mixture was stirred at 100 ° C. for 2 hours.

After cooling the reaction solution to room temperature, a part of the reaction solution was taken, dissolved in chloroform, 10% hydrochloric acid was added to separate the solutions, and the obtained organic layer was analyzed by gas chromatography. As a result, the conversion rate to I-TAI was 99. It was .43%.

The reaction solution was washed with 10% aqueous sodium hydrogen carbonate solution (20 mL), 10% aqueous sodium thiosulfate solution (20 mL), and water (20 mL). The organic layer was concentrated under reduced pressure, and the concentrated residue was quantified by gas chromatography. As a result, it was confirmed that I-TAI was contained in 11.75 g (yield from Br-TAI: 96.0%).

Zinc powder (7.45 g, 114 mmol) is suspended in THF (12.1 mL) and toluene (8.3 mL), and bromine (4.74 g, 29.7 mmol) is added dropwise at 26 to 30 ° C. over 70 minutes. , Stirred at the same temperature for 2 hours. Then, the crude I-TAI (11.75 g, 45.9 mmol) (concentrated residue) prepared above at 47 to 50 ° C. was added dropwise over 1 hour, and the mixture was stirred at 50 to 52 ° C. for 4 hours. Then, the reaction mixture was cooled to 30 ° C. and (4S, 5R) -1,3-dibenzyl-3,3a, 6,6a-tetrahydro-1H-thieno [3,4-d] imidazole-2,4-dione. (Hereinafter also referred to as DTL; 7.47 g, 22.1 mmol), toluene (19 mL) was added, and 10% Pd / C (174.8 mg, 0.165 mmol) of N, N-dimethylformamide (2. 4 mL) Suspension was added and stirred at the same temperature for 17 hours.

After completion of the reaction, 16% hydrochloric acid (24 mL) was added to the reaction solution at 25 ° C., the mixture was stirred at the same temperature for 5 hours, and then filtered. The obtained organic layer was washed with water (30 mL x 3), 10% aqueous sodium hydrogen carbonate solution (50 mL), 10% aqueous sodium thiosulfate solution (50 mL), and water (30 mL). The organic layer was concentrated and ethyl (3aS, 4Z, 6aR) -5- (1,3-dibenzyl-2,3,3a,4,6,6a-hexahydro-2-oxo-1H-thieno [3,4-" d] Imidazole-5-iriden) pentanoart (hereinafter, also referred to as DVE; 9.64 g, yield with respect to DTL: 96.9%) was obtained.

The results of infrared analysis (IR) and ¹ H-NMR measurement of the obtained DVE are shown.
IR (KBr) ν: 2932,1691 cm ^-1 .
^{1 1} H-NMR (400 MHz, CDCl ₃ ) δ: 7.08-6.95 (10H, m), 5.13 (1H, dd, J = 8.0Hz), 4.59 (2H, m), 3 .99-3.72 (6H, m), 2.71-2.62 (2H, m), 1.99-1.95 (2H, m), 1.88-1.72 (2H, m) , 1.45-1.35 (2H, m), 0.96 (3H, dd, J = 8.0Hz).

Example 4
I-TAI was prepared from Br-TAI using tetra-n-butylammonium bromide as a tetra-substituted ammonium salt, and the side chain was introduced into a biotin intermediate using the I-TAI.

Br-TAI (40.0 g, 191 mmol) and tetra-n-butylammonium bromide (TBAB, 3.7 g, 11.5 mmol) were dissolved in toluene (100 mL) in a reaction vessel and then sodium iodide at 25 ° C. (34.4 g, 230 mmol) and distilled water (1.0 mL) were added, and the mixture was stirred at 100 ° C. for 2 hours.

After cooling the reaction solution to room temperature, a part of the reaction solution was taken, dissolved in chloroform, water was added to separate the layers, and the obtained organic layer was analyzed by gas chromatography. As a result, the conversion rate to I-TAI was 98.77. %Met.

The above reaction solution was washed with 10% aqueous sodium hydrogen carbonate solution (50 mL), 10% aqueous sodium thiosulfate solution (50 mL), and water (50 mL), the obtained organic layer was concentrated under reduced pressure, and the concentrated residue was subjected to gas chromatography. As a result of quantification, it was confirmed that I-TAI was contained in 48.4 g (yield from Br-TAI: 99.0%).

Zinc powder (29.6 g, 453 mmol) was suspended in THF (48 mL) and toluene (34 mL), and bromine (15.1 g, 94.5 mmol) was added dropwise at 26 to 30 ° C. over 3.5 hours. Then, the crude I-TAI (48.4 g, 189 mmol) (concentrated residue) prepared above at 55 ° C. was added dropwise over 1.5 hours, and the mixture was stirred at 55 ° C. for 3 hours. Then, the reaction mixture was cooled to 30 ° C., DTL (45.1 g, 135 mmol) and toluene (97 mL) were added, and 10% Pd / C (1.24 g, 1.17 mmol) of N, N-dimethyl was added at the same temperature. A suspension of formamide (12 mL) was added and stirred at the same temperature for 15 hours.

After completion of the reaction, 16% hydrochloric acid (108 mL) was added to the reaction solution at 25 ° C., the mixture was stirred at the same temperature for 1 hour, and then filtered. Since the dehydration reaction in the presence of hydrochloric acid to make the side chain an unsaturated linear hydrocarbon side chain was insufficient, 10% hydrochloric acid (30 mL) was further added to the obtained filtrate, and then 3 at 40 ° C. Stir for hours. The obtained organic layer was washed with water (93 mL, 165 mL x 2), 10% aqueous sodium hydrogen carbonate solution (165 mL), 10% aqueous sodium thiosulfate solution (165 mL), and water (93 mL).

After concentrating the organic layer, toluene (80 mL) was added and concentration under reduced pressure was repeated twice. The obtained concentrated residue was dissolved in methanol (100 mL), activated carbon (Serakemu Co., Ltd. Snow A, 1.71 g) was added, and the mixture was stirred at 40 ° C. for 1 hour. The reaction solution was filtered to obtain DVE as a methanol solution (DVE 54.4 g, yield to DTL: 90.7%).

Claims (4)

(In the formula, R ¹ to R ³ may contain at least one group selected from a halogen atom, an ester group, a carboxyl group, an amide group, a nitrile group, a nitro group, an aldehyde group and a ketone group, and may contain an alkyl group. Alternatively, it is an aralkyl group or a hydrogen atom, and ^R1 to R3 may be the same group or different groups ^, respectively ^, and ^R1 to R3 may be an alkyl group or an aralkyl group. , May be bonded to each other to form a ring. X is a group selected from a fluorine atom, a chlorine atom, a bromine atom, a mesiloxy group or a tosiloxy group.)
The alkane derivative represented by
In an organic solvent,
Expressed by the following equation (2)

(In the formula, R ⁴ to R ⁷ are alkyl groups or aralkyl groups, which may be the same group or different groups, respectively. X is a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. , A hydroxyl group, or a hydrogen sulfate group.)
In the presence of a tetra-substituted ammonium salt
React by contacting with alkali metal iodide,
The following formula (3)

(In the formula, R ¹ to R ³ have the same meaning as those in the above formula (1).)
A method for producing an alkane iodide derivative, which comprises producing an alkane iodide derivative represented by. The method for producing an alkane iodide derivative according to claim 1, wherein the organic solvent is a non-polar solvent. The method for producing an alkane iodide derivative according to claim 1, wherein the alkane iodide is brought into contact with an alkali metal iodide salt in the presence of water. The alkane derivative represented by the formula (1) is the following formula (1A).

(In the formula, R is an alkyl group having 1 to 6 carbon atoms or an aralkyl group having 7 to 11 carbon atoms, and X is a chlorine atom or a bromine atom.)
It is a 5-halogenovaleric acid ester represented by
The alkane iodide derivative represented by the formula (3) is represented by the following formula (3A).

(In the formula, R is synonymous with that in the above formula (1A).)
The method for producing an alkane iodide derivative according to any one of claims 1 to 3, which is a 5-iodovaleric acid ester represented by.