JP2002193919A - Sulfone derivative and method for producing the same - Google Patents

Abstract

(57) Abstract: Provided is a sulfone derivative and a method for producing the same. SOLUTION: General formula (1) (Wherein, Ar is an aryl group which may have a substituent,
R ¹ represents a hydrogen atom or a protecting group for a hydroxyl group, and a wavy line represents one of E / Z geometric isomers or a mixture thereof. ) And a general formula (2) (Wherein, Ar represents the same meaning as described above) and a sulfone represented by the general formula (3): (Wherein, X represents a halogen atom, R represents a hydroxyl-protecting group, and wavy lines represent the same meaning as described above). For producing sulfone derivatives.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a sulfone derivative useful as an intermediate of a pharmaceutical, feed additive or food additive, for example, an intermediate of a retinol derivative, and a method for producing the same.

[0002]

2. Description of the Related Art Conventionally, a sulfone derivative represented by the following general formula (1) of the present invention has not been known. Further, the present inventors have disclosed in
As disclosed in JP-A-222479, a novel intermediate which is an important intermediate of retinol by a coupling reaction between a sulfone represented by the following general formula (2) and an allyl halide derived from a C10 alcohol (eg, geraniol). However, as a method for producing retinol, it has been desired to develop a more excellent production method from the viewpoints of the price of raw materials, purification of intermediates, and the number of steps.

[0003]

Under these circumstances, the present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have accomplished the present invention. That is, the present invention relates to the general formula (1) (Wherein, Ar is an aryl group which may have a substituent,
R ¹ represents a hydrogen atom or a protecting group for a hydroxyl group, and a wavy line represents one of E / Z geometric isomers or a mixture thereof. )); And a general formula (2) (Wherein, Ar represents the same meaning as described above) and a sulfone represented by the general formula (3): (Wherein X represents a halogen atom, R represents a hydroxyl-protecting group, and wavy lines represent the same meanings as described above), and reacted with an allyl halide derivative represented by the following formula in the presence of a base: It is intended to provide a method for producing the sulfone derivative represented by (1).

[0004]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. R in the sulfone derivative represented by the general formula (1)
¹ represents a hydrogen atom or a hydroxyl-protecting group, and R in the compound represented by the general formula (3) represents a hydroxyl-protecting group. Such hydroxyl-protecting groups include, for example, formyl, acetyl, ethoxyacetyl, fluoroacetyl,
Difluoroacetyl, trifluoroacetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, bromoacetyl, dibromoacetyl, tribromoacetyl,
Propionyl, 2-chloropropionyl, 3-chloropropionyl, butyryl, 2-chlorobutyryl, 3-chlorobutyryl, 4-chlorobutyryl, 2-methylbutyryl, 2-ethylbutyryl, valeryl, 2-methylvaleryl, 4-methylvaleryl, hexanoyl, isobutyryl, isovaleryl, Pivaloyl, benzoyl, o-chlorobenzoyl, m-chlorobenzoyl, p-chlorobenzoyl, o-hydroxybenzoyl, m-hydroxybenzoyl, p-hydroxybenzoyl, o-acetoxybenzoyl, o-methoxybenzoyl, m-methoxybenzoyl, p Acyl groups such as -methoxybenzoyl and p-nitrobenzoyl; silyls such as trimethylsilyl, triethylsilyl, t-butyldimethylsilyl and t-butyldiphenylsilyl , Tetrahydropyranyl,
Alkoxymethyl groups such as methoxymethyl, methoxyethoxymethyl and 1-ethoxyethyl, benzyl groups, p-
Methoxybenzyl group, t-butyl group, trityl group, methyl group, 2,2,2-trichloroethoxycarbonyl group,
An allyloxycarbonyl group and the like are mentioned, and an acyl group is usually preferably used.

Ar in the compound represented by the general formula (1) or (2) represents an aryl group which may have a substituent. Examples of the aryl group include a phenyl group and a naphthyl group. , A C1 to C5 linear or branched alkyl group, a C1 to C5 linear or branched alkoxy group, a halogen atom, a nitro group and the like. Specific examples of the substituent Ar include phenyl, naphthyl, o-tolyl, m-tolyl, p-tolyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-chlorophenyl, m-chlorophenyl and p-toluene.
Chlorophenyl, o-bromophenyl, m-bromophenyl, p-bromophenyl, o-iodophenyl, m-
Examples include iodophenyl, p-iodophenyl, o-fluorophenyl, m-fluorophenyl, p-fluorophenyl, o-nitrophenyl, m-nitrophenyl, p-nitrophenyl and the like.

X in the allyl halide derivative represented by the general formula (3) represents a halogen atom, and specific examples thereof include a chlorine atom, a bromine atom and an iodine atom.

The sulfones (2), which are the starting compounds of the present invention, are prepared, for example, by the method described in Chem. Lett. 479 (1975), and the allyl halide derivative (3) is prepared, for example, in US Pat. No. 4,175,204. According to the method described in this document, it can be simply produced from isoprene in two steps.

The sulfone derivative represented by the general formula (1) comprises a sulfone represented by the general formula (2) and a sulfone derivative represented by the general formula (3)
By reacting with an allyl halide derivative represented by the formula in the presence of a base. Examples of the base used in the above reaction include alkyllithium, alkali metal alkoxide, alkali metal amide, and alkali metal hydride.
Butyllithium, s-butyllithium, t-butyllithium, sodium methoxide, potassium methoxide, lithium methoxide, sodium ethoxide, potassium ethoxide, lithium ethoxide, potassium tert-butoxide, sodium tert-butoxide, lithium tert-butyl Butoxide, sodium t-amylate, potassium t-amylate, lithium amide, potassium amide, sodium amide, lithium diisopropylamide, sodium hexamethyldisilazide, potassium hexamethyldisilazide,
Lithium hexamethyldisilazide, sodium hydride,
Potassium hydride, lithium hydride and the like can be mentioned. These may be used in combination of two or more bases such as, for example, a combination of sodium t-butoxide and sodium hydride. For example, sodium t-butoxide may be prepared from t-butanol and sodium hydride. The above-mentioned bases may be used in the form of the respective bases described above, for example, in the system or in the system of lithium diisopropylamide from diisopropylamine and n-butyllithium. The amount of the base to be used is generally 0.5 to 3 based on the sulfones (2).
It is about mole times.

When an alkali metal hydride is used as the base, a compound having active hydrogen can be added as an additive. Examples of the compound having active hydrogen include alcohols, amines, sulfones, and sulfoxides. Specifically, for example, n-butyl alcohol, s-
Butyl alcohol, t-butyl alcohol, t-amyl alcohol, aniline, diisopropylamine, dimethyl sulfone, dimethyl sulfoxide and the like. The amount of the additive to be used is usually about 0.1 to 3 times by mole to the sulfones (2), but the amount of the solvent may be used. These may be used alone or in combination of two or more. Further, as an activator of an anion, a compound having a coordination property to an alkali metal, for example, a crown ether or tetramethylethylenediamine may be added, and as an activator of an allyl halide, halogen exchange is induced. For example, an alkali metal iodide or tetraalkylammonium iodide may be added.

The above reaction is usually carried out in an organic solvent, and the solvent used is acetonitrile, N, N-
Dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, sulfolane, 1,3-
Aprotic polar solvents such as dimethyl-2-imidazolidinone, 1-methyl-2-pyrrolidinone, diethyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, anisole, diglyme, triglyme,
Examples thereof include ether solvents such as tetraglyme, alcohol solvents such as t-butanol, and hydrocarbon solvents such as n-hexane, cyclohexane, n-pentane, benzene, toluene, and xylene. These may be used alone or in a mixture of two or more. Further, it is desirable to select an optimum solvent depending on the type of the base to be used.

The reaction temperature can be arbitrarily selected within the range of -78 ° C. to the boiling point of the solvent, but it is desirable to select an optimum reaction temperature depending on the type of the starting compound, base and solvent used. When the base to be used is of a type in which hydrogen is extracted from the substrate by an equilibrium reaction to generate an anion (for example, an alkoxide of an alkali metal), the temperature of anionization (reaction between the base and the sulfones (2)) is increased. By setting the temperature and setting the reaction temperature with the allyl halide derivative (3) low, the yield can also be improved. The reaction time varies depending on various conditions such as the starting compound used, the base, the solvent and the reaction temperature, but is usually in the range of about 5 minutes to 24 hours.

The reaction is preferably carried out under non-oxygen conditions, and is preferably carried out in an inert gas (nitrogen, argon) atmosphere, and the solvent used is preferably sufficiently degassed. Further, as a stabilizer, an antioxidant such as 3,5-di-tert-butyl-4-hydroxytoluene (BHT), 2- & 3-tert-butyl-4-hydroxyanisole (BHA), vitamin E, and ethoxyquin is added. More preferred. After the reaction, the sulfone derivative (1) can be produced by ordinary post-treatments such as extraction, washing, crystallization, and various kinds of chromatography. Depending on the reaction conditions, about 10 to 30% of the alcohol in which R ¹ is a hydrogen atom in the sulfone derivative (1) may be obtained, but can be reprotected by a conventional method.

The sulfone derivative (1) of the present invention (in which a protecting group is introduced when R ¹ is a hydrogen atom) can be derived into retinol according to the following scheme. That is, the sulfone derivative (1) is subjected to a sulfonation reaction using an alkali metal aryl sulfinate to obtain an allyl sulfone derivative (4), and the disulfone derivative obtained by reacting the allyl sulfone derivative (3) with the derivative Retinol can be easily obtained by reacting (5) with a base. INDUSTRIAL APPLICABILITY The sulfone derivative (1) of the present invention can be an important intermediate of retinol useful as a pharmaceutical, feed additive, or food additive.

[0014]

The use of the sulfone derivative (1) of the present invention is advantageous in that retinol can be derived in a short process using isoprene, which is less expensive than C10 alcohols.

[0015]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto.

(Embodiment 1) A solution of 224 mg (2 mmol) of potassium t-butoxide dissolved in 6 ml of DMF was cooled to -60 ° C, and 585 mg of sulfone (I) (2 mmol) was added.
A solution of l) in DMF (4 ml) was added dropwise over 20 seconds. After the addition, the mixture was kept at the same temperature for 30 minutes. Then, allyl halide (II) (9
(6%) A solution of 215 mg (1 mmol) in DMF (4 ml) was added dropwise at the same temperature for 5 minutes, and the mixture was stirred for 3 hours. After the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The obtained organic layer was sequentially washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude product as a yellow oil. When the obtained crude product was quantified by high performance liquid chromatography, the sulfone derivatives (III) and (IV) were obtained in yields of 71.2% and 15.4%, respectively. Sulfone derivative (III) ¹ H-NMR δ (CDCl ₃ ) 0.73 (3H, s), 0.99 (3H, s), 1.25-1.64 (7H, m), 1.97-
2.04 (8H, m), 2.37 (3H, m), 2.54-2.96 (2H, m), 3.74-
3.87 (1H, m), 4.37 (2H, d, J = 7Hz), 5.29 (1H, t, J = 7H
z), 7.23 (2H, d, J = 8 Hz), 7.69 (2H, d, J = 8 Hz) sulfone derivative (IV) ¹ H-NMR δ (CDCl ₃ ) 0.82 (3H, s), 1.04 (3H, s ), 1.22-1.57 (4H, m), 1.30 (3
H, s), 2.00 (3H, s), 2.03-2.24 (2H, m), 2.33 (1H, br.
s), 2.42 (3H, m), 2.59 (1H, dd, J = 7Hz, 14Hz), 2.99 (1
H, dd, J = 7Hz, 14Hz), 3.91 (1H, t, J = 7Hz), 3.99 (2H,
d, J = 7Hz), 5.40 (1H, t, J = 7Hz), 7.31 (2H, d, J = 8Hz),
7.75 (2H, d, J = 8Hz)

(Example 2) 224 mg of potassium t-butoxide
(2 mmol) dissolved in 6 ml of DMF was cooled to −20 ° C.
A solution of 585 mg (2 mmol) of sulfone (I) in DMF (4 ml) was added dropwise over 20 seconds, and the mixture was kept at the same temperature for 5 minutes. −60 ° C
And then allyl halide (II) (96%) 215 mg
A solution of (1 mmol) in DMF (3 ml) was added dropwise at the same temperature over 5 minutes and stirred for 3 hours. After the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The obtained organic layer was sequentially washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude product as a yellow oil. When the obtained crude product was quantified by high performance liquid chromatography, the sulfone derivative (III) was obtained in a yield of 99.5%.

Example 3 Sodium t-butoxide 116
A solution of mg (1.2 mmol) in 6 ml of DMF was cooled to 0 ° C., and a solution of 876 mg (3 mmol) of sulfone (I) in 4 ml of DMF was added.
The solution was dropped for 20 seconds, kept at the same temperature for 5 minutes, and then cooled to -20 ° C. Then, 215 mg of allyl halide (II) (96%) (1 m
mol) in DMF (3 ml) was added dropwise over 5 minutes at the same temperature and stirred for 3 hours. After the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The obtained organic layer was sequentially washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude product as a yellow oil. When the obtained crude product was quantified by high performance liquid chromatography, the sulfone derivative (III) was obtained with a yield of 65.9%.

Example 4 Sulfone (I) 585 mg (2 mmol)
Was dissolved in 6 ml of tetrahydrofuran (THF), cooled to -60 ° C, and sodium hexamethyldisilazide was dissolved.
1.16 ml (1.2 mmol) of a 0.96 mol / l THF solution was added dropwise over 20 seconds, and the mixture was kept at the same temperature for 30 minutes. Then allyl halide
(II) A solution of 215 mg (1 mmol) (96%) in THF (3 ml) was added dropwise at the same temperature over 5 minutes, and the mixture was stirred for 3 hours. After the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The obtained organic layer is a saturated aqueous solution of sodium hydrogen carbonate,
The extract was washed successively with saturated saline, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude product as a yellow oil. When the obtained crude product was quantified by high performance liquid chromatography, the sulfone derivative (III) was obtained at a yield of 70.
Obtained at 0%.

Example 5 Except that the 0.96 mol / l THF solution of sodium hexamethyldisilazide in Example 4 was replaced with a 1.0 mol / l THF solution of lithium diisopropylamide, the same reaction and post-treatment were performed. Was. When the obtained crude product was quantified by high performance liquid chromatography, the sulfone derivative (III) was obtained in a yield of 59.4%.

Example 6 Sodium hydride (60%, oil suspension) (80 mg, 2 mmol) was suspended in DMF (5 ml), t-butanol (88.9 mg, 1.2 mmol) was added, and the mixture was heated and stirred at 50 ° C. for 2 hours. Then, 585 mg (2 mmol) of sulfone (I) and 4 mg (0.02 mmol) of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) were added to D.
An MF (3 ml) solution was added dropwise at the same temperature, and the mixture was stirred for 3 minutes.
After cooling to −20 ° C., allyl halide (II) (96%) 215 mg (1 mmo
A solution of l) in DMF (2 ml) was added dropwise over 1 minute, and the mixture was stirred at the same temperature for 2 hours. After the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The obtained organic layer was sequentially washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated saline solution,
After drying over anhydrous magnesium sulfate, the solvent was distilled off to obtain a crude product as a yellow oil. When the obtained crude product was quantitatively analyzed by high performance liquid chromatography,
The sulfone derivative (III) was obtained in a yield of 59.5%.

Example 7 40 mg (1 mmol) of sodium hydride (60%, oil suspension) was suspended in 5 ml of DMF, 99.1 mg (1 mmol) of sodium t-butoxide was added, and the temperature was raised to 40 ° C. Then, 585 mg (2 mmol) of sulfone (I) and 4 mg (0.02 mmol) of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) were added to D.
An MF (3 ml) solution was added dropwise at the same temperature, and the mixture was stirred for 20 minutes. Then, the mixture was cooled to −20 ° C. and stirred for 30 minutes. Then, a solution of 215 mg (1 mmol) of allyl halide (II) (96%) in DMF (2 ml) was added dropwise over 1 minute, and the mixture was stirred at the same temperature for 2 hours. After the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The obtained organic layer is a saturated aqueous solution of sodium hydrogen carbonate,
The extract was washed successively with saturated saline, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude product as a yellow oil. When the resulting crude product was quantitatively analyzed by high performance liquid chromatography, the sulfone derivative (III) was 59.6%
Was obtained in a yield of

Example 8 In a nitrogen atmosphere, 48 mg (1.2 mmol) of sodium hydride (60%, oil suspension) was suspended in 1 ml of dimethyl sulfoxide (DMSO), and the mixture was stirred at room temperature for 3 hours. Then 585 mg (2 mmol) of sulfone (I) in DMSO (6 m
l) The solution was added dropwise at the same temperature and stirred for 1 hour. Next, a solution of 211 mg (1 mmol) of allyl halide (II) (98%) in DMSO (1 ml) was added dropwise over 1 minute, and the mixture was stirred at the same temperature for 5 minutes. After the reaction, water was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off.
Quantitative analysis of the obtained crude product by high performance liquid chromatography showed that the sulfone derivative (III) was obtained at a yield of 37.6%.

Example 9 Sodium t-butoxide 11
A solution of 6 mg (1.2 mmol) dissolved in 6 ml of DMF was cooled to 0 ° C., and a solution of 585 mg (2 mmol) of sulfone (I) in 4 ml of DMF was added.
Drops over 20 seconds, then 15-crown-5 22 mg (0.
1 mmol) and kept warm for 5 minutes. Thereafter, the mixture was cooled to −20 ° C. and 215 mg (1.0 mmol) of allyl halide (II) (96%) in DM
An F (4 ml) solution was added dropwise at the same temperature over 5 minutes, and the mixture was stirred for 3 hours. After the reaction, poured into a saturated aqueous ammonium chloride solution,
Extracted with ethyl acetate. The obtained organic layer was sequentially washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude product as a yellow oil. When the obtained crude product was quantified by high performance liquid chromatography, the sulfone derivative (III) was obtained with a yield of 69.6%.

Example 10 The 15-crown-5 of Example 9 was replaced with 38 mg (0.1 mmol) of tetrabutylammonium iodide.
The reaction and post-treatment were performed in exactly the same manner as in l) except that the reaction was carried out. When the obtained crude product was quantified by high performance liquid chromatography, the sulfone derivative (III) was obtained at a yield of 65.2%.
Was obtained.

(Embodiment 11) A solution of 115 mg (1.2 mmol) of potassium t-butoxide dissolved in 5 ml of DMF was cooled to −20 ° C., and 585 g of sulfone (I) (2 mm
ol) in DMF (3 ml) was added dropwise and stirred at the same temperature for 5 minutes. After cooling to −30 ° C., allyl halide (V) 269 mg (1 m
mol) in DMF (2 ml) was added dropwise and stirred for 2.5 hours.
After the reaction, water was added, and the mixture was extracted with ethyl acetate. After the obtained organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the obtained crude product was purified by silica gel thin-layer chromatography to obtain the sulfone derivative (VI) in a yield.
Obtained at 69.5%. Sulfone (VI) ¹ H-NMR δ (CDCl ₃ ) 0.82 (3H, s), 1.08 (3H, s), 1.39 (3H, s), 1.39-1.70 (4
H, m), 2.03 (3H, s), 2.00-2.22 (2H, m), 2.41 (3H, s),
2.68 (1H, dd, J = 7Hz, 14Hz), 3.05 (1H, dd, J = 7Hz, 14
Hz), 3.93 (1H, t, J = 7Hz), 4.70 (2H, d, J = 7Hz), 5.51
(1H, t, J = 7Hz), 7.27-8.04 (9H, m)

(Reference Example 1) Under a nitrogen atmosphere, palladium chloride 9 mg (0.05 mmol), p-
178 mg (1 mmol) of sodium toluenesulfinate was suspended in 2 ml of methanol, and 62 mg of triphenyl phosphite (0.2 mg) was suspended.
mmol) and 211 mg (98.3%) of the sulfone derivative (III) (0.5 mmo
A solution of l) in tetrahydrofuran (THF) (2 ml) was added, and the mixture was stirred at room temperature for 1.5 hours, heated to 60 ° C., and stirred for 5.5 hours. After the reaction, water and saturated saline were added, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate. Next, the crude product obtained by distilling off the solvent was quantitatively analyzed by high performance liquid chromatography, and the yield of the allyl sulfone derivative (VII) was 89.1%.

(Reference Example 2) Sodium hydride (60%, oil suspension) 19 mg (0.48 mmol)
Was dissolved in 6 ml of DMF, cooled to 0 ° C., and a solution of 190 mg (0.37 mmol) of the allyl sulfone derivative (VII) in 3 ml of DMF was added dropwise over 20 seconds, and the mixture was kept warm for 20 minutes. Then, 88 mg (0.41 mmol) of allyl halide (II) (96%) in DMF (3 ml)
The solution was added dropwise at the same temperature for 5 minutes, and then naturally warmed to room temperature and stirred for 3 hours. After the reaction, the reaction solution was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The obtained organic layer was sequentially washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off to obtain a crude product as a yellow oil. When the obtained crude product was quantified by high performance liquid chromatography, the yield of the disulfone derivative (VIII) was 94.8%.

(Reference Example 3) Disulfone derivative (VIII) 256 mg (0.4 mmol) was treated with hexane (BHT
After dissolving in 2 ml, 95% potassium hydroxide 240 mg (4
mmol), 7 mg (0.2 mmol) of methanol and 4 mg (0.02 mmol) of benzyltriethylammonium chloride, and the mixture was stirred at 30 ° C. for 18 hours. After the reaction, saturated saline was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was sequentially washed with water and saturated saline, dried over anhydrous sodium sulfate, and then the solvent was distilled off to obtain crude retinol as a red oil. The obtained crude retinol was acetylated by a conventional method and quantified by high performance liquid chromatography. As a result, the yield of retinol acetate (IX) was 91.3%.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Shinzo Seko 2-10-1 Tsukahara, Takatsuki-shi, Osaka Sumitomo Kagaku Kogyo Co., Ltd. F-term (reference) 4H006 AA01 AA02 AC24 AC62 BE90 TA02 TB04 TB32

Claims (7)

[Claims] 1. The general formula (1) (Wherein, Ar is an aryl group which may have a substituent,
R ¹ represents a hydrogen atom or a protecting group for a hydroxyl group, and a wavy line represents one of E / Z geometric isomers or a mixture thereof. ). 2. The general formula (2) (Wherein, Ar represents the same meaning as described above) and a sulfone represented by the general formula (3): (Wherein X represents a halogen atom, R represents a hydroxyl-protecting group, and wavy lines represent the same meanings as described above), and reacted with an allyl halide derivative represented by the following formula in the presence of a base: A method for producing the sulfone derivative represented by (1). 3. The process according to claim 2, wherein the base is an alkyl lithium, an alkali metal alkoxide, an alkali metal amide or an alkali metal hydride. 4. The method according to claim 3, wherein the alkali metal alkoxide is sodium t-butoxide, potassium t-butoxide, sodium t-amylate, or potassium t-amylate. 5. The amide of an alkali metal is lithium diisopropylamide, sodium hexamethyldisilazide,
The production method according to claim 3, wherein the production method is potassium hexamethyldisilazide. 6. The hydride of an alkali metal is sodium hydride, potassium hydride or lithium hydride.
Production method described in 1. 7. The method according to claim 2, wherein R is an acyl group.