KR20150121159A - Method for producing 4-halosenecioic acid derivative - Google Patents

Abstract

It is an object of the present invention to provide a method for producing a 4-halenesic acid derivative at a high yield and at low cost. A process for producing a compound represented by the general formula (2): wherein R is as defined above (wherein R is as defined above), which comprises reacting an allyl alcohol derivative represented by the general formula (1) And X represents a halogen atom). ≪ / RTI >

Description

METHOD FOR PRODUCING 4-HALOSENECIOIC ACID DERIVATIVE [0002]

The present invention relates to a process for the production of 4-halenesicic acid derivatives useful as intermediates in the production of pesticides.

The 4-halenesic acid derivative can be converted into a Wittig-Horner reagent by reaction with triethyl phosphite, and thus is useful as an agrochemical intermediates (for example, Patent Document 1, Patent Document 2 , Non-Patent Document 1).

As a process for producing a 4-halenenic acid derivative, there is disclosed a process for producing a 4-halenenic acid derivative by a halogenation reaction of a 3-methylcrotonic acid ester (see, for example, Non-Patent Document 1). According to this method, since the polyhalogenated product is obtained as a by-product, it is difficult to say that it is an efficient method. A process for producing a 4-halenesioic acid derivative using ethyl diethylphosphonoacetate and α-haloacetone as a starting material has also been disclosed (see, for example, Non-Patent Document 2) . On the other hand, a method of converting a secondary allyl alcohol into a primary allyl halide with the potential of a double bond using a halogenating agent has been reported. However, in general, as a product, there is a method in which a primary allyl halide and an allyl substituent A mixture of halogenated allyl halides in the presence of a halogen is provided (see, for example, Non-Patent Document 3).

There has been no report on the production method of halogenating a 4-halenesioic acid derivative using the allyl alcohol derivative of the present invention as a raw material.

International Publication No. 2012/147831 WO 94/24082

Tetrahedron, 42, 2635-2642 (1986) Organic Reactions, 25, 73-253 (1977) Tetrahedron, 63, 2712-2723 (2007)

In the conventional 4-halenesic acid derivative production method, by-products are generated, resulting in a problem that the total yield is low and the production cost is high. It is an object of the present invention to provide a process for producing a 4-halenesicioic acid derivative at a high selectivity and a high yield using an inexpensive raw material.

DISCLOSURE OF THE INVENTION The inventors of the present invention have made intensive investigations in view of the above problems and have found that a 4-halosenesiic acid derivative can be produced from an allyl alcohol derivative represented by the general formula (1) at a high selectivity and a high yield , Thereby completing the present invention.

That is, the present invention provides a compound represented by the general formula (1):

(2), wherein the allyl alcohol derivative represented by the general formula (2): wherein R represents a protecting group, is reacted with a halogenating agent.

(Wherein R has the same meaning as defined above and X represents a halogen atom).

The present invention also relates to a compound represented by the general formula (1):

(3), wherein the allyl alcohol derivative represented by the general formula (3): (wherein R represents a protecting group) is reacted with a halogenating agent at a temperature of 10 ° C or lower.

(Wherein R has the same meaning as defined above and X represents a halogen atom).

The present invention also relates to a compound represented by the general formula (3):

(2), wherein the allyl halide derivative represented by the general formula (2): wherein R represents a protecting group and X represents a halogen atom, is reacted with a halide at a temperature higher than 10 ° C.

(Wherein R and X have the same meanings as defined above).

By halogenating the allyl alcohol derivative (1) according to the present invention, the 4-halenesioic acid derivative (2) useful as a production intermediate of the pesticide can be produced with high selectivity and high yield. Further, the method of the present invention is excellent in industrial and economical aspects because it does not use expensive raw materials and has high selectivity and yield.

Hereinafter, the present invention will be described in detail. First, terms used in the present specification and claims will be described. Each term has the following significance, unless otherwise indicated.

In the present invention, " protecting group " means a protecting group which can be cleaved by a chemical method such as hydrolysis, hydrolysis, electrolysis, and photo decomposition commonly used in organic synthesis chemistry. In particular, the term " protecting group " relating to R of the present invention means a protecting group which is a protecting group for a carboxyl group, and which can be cleaved by other chemical methods without being cleaved under the reaction conditions of the production method of the present invention. Such protecting groups are well known to those skilled in the art by reference, for example, in Organic Synthesis Chemistry, such as Protective Groups in Organic Synthesis (T.W. Greene et al., John Wiley & Sons, Inc.). Typically, R is an alkyl group having 1 to 6 carbon atoms or an aralkyl group having 7 to 19 carbon atoms.

In the present invention, the "alkyl group having 1 to 6 carbon atoms" alone or in combination with another term means a monovalent group of a straight or branched aliphatic saturated hydrocarbon having 1 to 6 carbon atoms, Propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl and hexyl. The "alkoxy group having 1 to 6 carbon atoms" means a group R'O- (wherein R 'is an alkyl group having 1 to 6 carbon atoms), and a methoxy group, ethoxy group, propyloxy group, An isobutyloxy group, a sec-butyloxy group, a tert-butyloxy group, and a hexyloxy group.

In the present invention, "aryl" or "aryl of 6 to 18 carbon atoms" means a monovalent group of an aromatic hydrocarbon having 6 to 18 carbon atoms, and examples thereof include a phenyl group, a naphthyl group and an anthryl group. Also included are those in which the monovalent group of the aromatic hydrocarbon is substituted by an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a halogen atom, or the like. Methylphenyl group (o-tolyl group), 4-methylphenyl group (p-tolyl group), 2,4-di-t- 4-methoxyphenyl group, 4-chlorophenyl group, and the like.

In the present invention, the "aralkyl group having 7 to 19 carbon atoms" means an arylalkyl group having 7 to 19 carbon atoms (wherein the aryl moiety is aryl having 6 to 18 carbon atoms and the alkyl moiety is an alkyl group having 1 to 6 carbon atoms) Benzyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1-anthrylmethyl group, 2-anthrylmethyl group, 9-anthrylmethyl group and the like.

Examples of the "halogen atom" in the present invention include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

Next, the manufacturing method of the present invention will be described in detail. The method for producing the 4-halenesicioic acid derivative (2) of the present invention is as shown in the following scheme.

(Wherein R and X have the same meanings as defined above)

Step 1 is a step of reacting an allyl alcohol derivative (1) with a halogenating agent to prepare a 4-halenesioic acid derivative (2).

The allyl alcohol derivative (1) as a starting material of the production method of the present invention can be synthesized in accordance with a known method (for example, Japanese Patent Application Laid-open No. 60-179147).

In the reaction of the step 1, a halogenating agent selected from a fluorinating agent, a chlorinating agent, a brominating agent and an iodinating agent is used in accordance with the aimed 4-halenesioic acid derivative (2). The halogenating agent is known to a person skilled in the art and can be a reagent described in a literature or a reference document (for example, Comprehensive Organic Transformations; Wiley-VCH; p689-697 (1999)). Such reagents are commercially available or can be prepared from commercially available reagents.

Examples of the fluorinating agent include N, N-diethyl-1,1,2,3,3,3-hexafluoropropylamine, (2-chloro-1,1,2-trifluoroethyl) Nitrogen-containing fluorinating agents; Phosphorus-containing fluorinating agents such as triphenylphosphine difluoride, diphenylphosphine trifluoride and the like; Sulfur-containing fluorinating agents such as diethylamino trifluoride, bis (2-methoxyethyl) amino sulfur trifluoride and the like; Hydrogen fluoride, hydrogen sulfide pyridinium salts, and the like.

A nitrogen-containing chlorinating agent such as (1-chloro-2-methyl-1-propenyl) dimethylamine as a chlorinating agent; Chlorine / triaryl phosphine, N-chlorosuccinic imide / triarylphosphine, 1,3-dichloro-5,5-dimethylhydantoin / triarylphosphine, carbon tetrachloride / triarylphosphine, chlorine / phosphorous triaryl Containing chlorine such as N-chlorosuccinic acid imide / triaryl phosphite, 1,3-dichloro-5,5-dimethylhydantoin / triaryl phosphorous acid, carbon tetrachloride / triaryl phosphorus trioxide, phosphorus trichloride, issue; Sulfur-containing chlorinating agents such as N-chlorosuccinic acid imide / dimethyl sulfide, p-toluenesulfonic acid chloride, methanesulfonic acid chloride, thionyl chloride and the like; Chlorine, trimethylsilyl chloride, zinc chloride, titanium chloride, hydrogen chloride, and the like.

Nitrogen-containing brominating agents such as (1-bromo-2-methyl-1-propenyl) dimethylamine as a brominating agent; Bromine / triarylphosphine, N-bromosuccinimide / triarylphosphine, 1,3-dibromo-5,5-dimethylhydantoin / triarylphosphine, carbon tetrabromide / triarylphosphine, Bromine / triaryl phosphite, N-bromosuccinimide / triaryl phosphite, 1,3-dibromo-5,5-dimethylhydantoin / triaryl phosphite, triaryl carbon tetrabromide / triaryl phosphite, Phosphorus-containing brominating agents such as phosphorus pentabromide, phosphorus pentabromide, phosphorus pentabromide, phosphorus pentabromide, Sulfur-containing brominating agents such as N-bromosuccinic acid imide / dimethyl sulfide, thionyl bromide and the like; Bromine, trimethylsilyl bromide, aluminum bromide, titanium bromide, hydrogen bromide and the like.

A nitrogen-containing iodinating agent such as (1-iodo-2-methyl-1-propenyl) dimethylamine as an iodinating agent; Iodine / triarylphosphine, N-iodosuccinic acid imide / triarylphosphine, 1,3-diiodo-5,5-dimethylhydantoin / triarylphosphine, carbon tetraiodide / triarylphosphine, Containing iodine such as iodine / triaryl phosphite, N-iodosuccinic acid imide / triaryl phosphite, 1,3-diiodo-5,5-dimethylhydantoin / triaryl phosphite, triaryl iodide / issue; Sulfur-containing iodinating agents such as N-iodosuccinic acid imide / dimethyl sulfide and thionyl iodide; Iodine, trimethylsilyl iodide, magnesium iodide, zinc iodide, hydrogen iodide, and the like.

Examples of the triarylphosphine usable as the halogenating agent include triphenylphosphine, tri (p-tolyl) phosphine, tris (4-methoxyphenyl) phosphine, tris (4-chlorophenyl) . From the viewpoint of good yield, it is preferable to use triphenylphosphine. Examples of triaryl phosphites usable as the halogenating agent include triphenyl phosphite, phosphorous tri (p-tolyl), and phosphorous tri (2,4-di-t-butylphenyl). From the viewpoint of good yield, it is preferable to use triphenyl phosphite and phosphorous acid tri (p-tolyl).

Commercially available products such as chlorine / triarylphosphine, bromine / triarylphosphine and iodine / triarylphosphine may be used, but those formed in the system from triarylphosphine and chlorine, bromine or iodine, that is, The preparation may be used as it is. Similarly, commercially available products such as chlorine / phosphorous triaryl bromine / phosphorous triaryl and iodine / phosphorous triaryl may be used, but those formed in the system from triaryl phosphite and chlorine, bromine or iodine, It may be used as it is.

Examples of the halogenating agent include nitrogen-containing halogenating agents (that is, nitrogen-containing fluorinating agents, nitrogen-containing chlorinating agents, nitrogen-containing brominating agents, nitrogen-containing iodinating agents) Containing brominating agent, phosphorus containing iodinating agent) and at least one member selected from the group consisting of sulfur-containing halogenating agents (i.e., sulfur-containing fluorinating agents, sulfur-containing chlorinating agents, sulfur- desirable.

From the viewpoint of the yield, the production method of the 4-halenesioic acid derivative of the general formula (2) in which the halogenating agent is a brominating agent and X is a bromine atom is preferred.

Among the brominating agents, especially bromine / triarylphosphine, N-bromosuccinimide / triarylphosphine, 1,3-dibromo-5,5-dimethylhydantoin / triarylphosphine, bromine / Triaryl phosphoric acid, triaryl N-bromosuccinic acid imide / triaryl phosphorous acid, 1,3-dibromo-5,5-dimethylhydantoin / triaryl phosphorous acid, phosphorus tribromide, phosphorus pentabromide and phosphorus oxybromide It is preferred to use at least one phosphorus containing brominating agent selected. Examples of the brominating agent include bromine / triphenylphosphine, N-bromosuccinic acid imide / triphenylphosphine, 1,3-dibromo-5,5-dimethylhydantoin / triphenylphosphine, bromine / Triphenyl, N-bromosuccinic acid imide / triphenyl phosphite, 1,3-dibromo-5,5-dimethylhydantoin / triphenyl phosphite, bromine / phosphorous acid tri (p- tolyl), N-bromosuccinic acid It is more preferable to use imide / phosphorous acid tri (p-tolyl) and 1,3-dibromo-5,5-dimethylhydantoin / phosphorous acid tri (p-tolyl).

The molar ratio of the allyl alcohol derivative (1) to the halogenating agent is preferably 1: 1 to 1: 5. Among them, 1: 1 to 1: 3 is more preferable in terms of good yield.

In the reaction of Step 1, the reaction can be carried out in the presence of a base in order to improve the yield. Examples of the base that can be used include metal hydrides such as sodium hydride, potassium hydride and calcium hydride; Aromatic amines such as imidazole, pyridine, 2,6-lutidine, s-collidine; Cyclic amines such as N-methylpyrrolidine and N-methylpiperidine; Aliphatic amines such as tri (C ₁ -C ₄ alkyl) amines including ethyldiisopropylamine, triethylamine and tributylamine; And inorganic salts such as sodium hydroxide, potassium hydroxide and potassium carbonate. In view of good yield, it is preferred to use aromatic amines or aliphatic amines, and it is also preferred to use pyridine or tri (C ₁ -C ₄ alkyl) amines.

The amount of the base to be used is preferably about 1 to 5 moles per 1 mole of the allyl alcohol derivative (1).

In the reaction of Step 1, a halide of the same halogen species as that of the halogenating agent to be used may be added in order to improve the yield. The halide is not particularly limited as long as it is capable of supplying a halide ion. An aqueous solution of a hydrogen halide such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, or hydroiodic acid; Halides of alkali metals or alkaline earth metals such as lithium, sodium, potassium, magnesium and calcium; Halides of transition metals such as zinc and copper; Amines such as aliphatic amines, aromatic amines, or hydrohalide hydrohalides of ammonia; And quaternary ammonium: NR " ₄ ⁺ (wherein R" each independently represents an alkyl group or an aryl group having 1 to 6 carbon atoms). Thus, specifically, when a fluorinating agent is used as the halogenating agent, examples of the halide include lithium fluoride, sodium fluoride, potassium fluoride, ammonium fluoride, tetrabutylammonium fluoride, and the like. When a chlorinating agent is used as the halogenating agent, examples of the halide include lithium chloride, sodium chloride, potassium chloride, ammonium chloride, tetrabutylammonium chloride and the like. When a brominating agent is used as the halogenating agent, examples of the halide include lithium bromide, sodium bromide, potassium bromide, ammonium bromide, tetrabutylammonium bromide, and the like. When an iodinating agent is used as the halogenating agent, examples of the halide include lithium iodide, sodium iodide, potassium iodide, lithium iodide, ammonium iodide and tetrabutylammonium iodide. Halides of alkali metals or halides of quaternary ammonium are preferred, and halides of lithium, sodium, potassium or tetra (C ₁ -C ₄ alkyl) ammonium are more preferred.

The amount of the halide to be used is preferably about 0.01 to 5 mol per 1 mol of the allyl alcohol derivative (1).

The solvent that can be used in the reaction of Step 1 may be any solvent that does not inhibit the reaction. Specific examples include ether solvents such as tetrahydrofuran, diethyl ether, 1,4-dioxane, methyl-tert-butyl ether, 1,2-dimethoxyethane and cyclopentyl methyl ether; Hydrocarbon solvents such as hexane, pentane and cyclohexane; Aromatic hydrocarbon solvents such as benzene, toluene, xylene, and mesitylene; Halogenated aromatic hydrocarbon solvents such as chlorobenzene, dichlorobenzene and trichlorobenzene; Amide solvents such as N, N-dimethylformamide, N-methyl-2-pyrrolidone and 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidone; Alcohol solvents such as methanol and ethanol; Dimethyl sulfoxide, water and the like. Two or more of these solvents may be mixed and used. Among them, it is preferable to use halogenated aromatic hydrocarbon solvents such as chlorobenzene and dichlorobenzene in view of good yield.

Although the reaction temperature is not particularly limited, it can be usually carried out at a temperature appropriately selected from the range of -78 ° C to 180 ° C. From the viewpoint of the reaction rate, the range of from above 10 DEG C to 130 DEG C is preferable, and the range from room temperature (about 20 DEG C) to 100 DEG C is more preferable.

There is no particular limitation on the method of isolating the object from the solution after the reaction. For example, the object can be obtained by a general method such as solvent extraction, column chromatography, preparative thin layer chromatography, preparative liquid chromatography, recrystallization or sublimation.

Step 2 is a step of reacting an allyl alcohol derivative (1) with a halogenating agent at a temperature of 10 ° C or lower to prepare an allyl halide derivative (3). The reaction conditions such as a halogenating agent, a base and a solvent, and preferred embodiments thereof are in accordance with Step 1, except that the temperature condition and the halide are not added.

The method for isolating an object from the solution after the reaction in Step 2 is also not particularly limited. For example, an object can be obtained by a general method such as solvent extraction, column chromatography, preparative thin layer chromatography, and preparative liquid chromatography.

Step 3 is a step of reacting an allyl halide derivative (3) with a halide at a temperature higher than 10 캜 to prepare a 4-halenesioic acid derivative (2). The halides that can be used correspond to the halides exemplified in Step 1. The amount of the halide to be used is preferably 0.01 to 5 mol per 1 mol of the allyl halide derivative (3).

The reaction solvent that can be used is the solvent exemplified in Step 1, but it is preferable to use an amide-based solvent such as N, N-dimethylformamide or N-methyl-2-pyrrolidone. The reaction temperature can be set at a temperature appropriately selected from a range of more than 10 ° C to 180 ° C. And more preferably in the range of room temperature (about 20 ° C) to 100 ° C.

Example

Hereinafter, the present invention will be described more specifically by way of examples, but the present invention is not limited to these examples. In the following examples, the gas chromatograph (GC) used for the purity measurement and the measurement conditions thereof are shown.

Device: GC-2010 (Shimatsu Seisakusho Co., Ltd.)

Column: ULTRA1 (Agilent Technologies)

25m x I.D.0. 32 mm, 0.52 탆df

Column temperature: 100 占 폚? [10 占 폚 / min]? 280 占 폚

Injection temperature: 300 ° C

Carrier gas: Helium gas

Detector: Hydrogen Ionization Detector (FID)

The measurement conditions of the NMR spectra of the compounds isolated in the examples are as follows.

Apparatus: AVANCE 400 (Bruker)

And a solution prepared by mixing the compound with chloroform (manufactured by Cambridge Isotope Laboratories, Inc., containing 0.05% TMS) was prepared and subjected to ¹ H-NMR measurement.

[Example 1] Preparation of ethyl 4-bromocenesioate

2.8 g (9 mmol) of triphenyl phosphite was added to 10 mL of chlorobenzene, cooled to 5 캜 or lower, and 1.4 g (9 mmol) of bromine was added dropwise. After 30 minutes of reaction, a mixed solution of 1 g (7 mmol) of ethyl 2-hydroxy-3-methyl-3-butenoate, 0.9 g (9 mmol) of triethylamine and 2 mL of chlorobenzene was added dropwise. After completion of the dropwise addition, the reaction was carried out at 80 DEG C for 1 hour. When the reaction rate was confirmed by GC, the intended ethyl 4-bromoseneceinate was 94% (mixture of E-isomer and Z-isomer).

20 mL of water was added to the reaction solution, and the organic layer was separated, and the residue was purified by silica gel column chromatography (ethyl acetate / hexane; 1/2) to obtain 86% of ethyl 4-bromoseneceinate Mixture).

^{1 H-NMR (400㎒, CDCl} 3) E sieve; δ: 5.96 (1H, s ), 4.18 (2H, q, J = 8.0㎐), 3.94 (2H, s), 2.28 (3H, s), 1.29 (2H, s), 4.18 (2H, q, J = 8.0 Hz), 2.05 (3H, s), 1.29 (3H, t, J = 8.0 Hz).

[Example 2-12]

The reactions of Examples 2 to 12 were carried out in the same manner as in Example 1. In Examples 11 to 12, 1.3 equivalents of halide was used for ethyl 2-hydroxy-3-methyl-3-butenoate. Table 1 shows the brominating agent, base, halide, reaction temperature, reaction time, and yield (%) of the target used in the examples.

[Example 13] Preparation of ethyl 4-iodosenehexanoate

2.8 g (9 mmol) of triphenyl phosphite in 10 mL of chlorobenzene was added, and the mixture was cooled to 5 DEG C or lower, and 2.3 g (9 mmol) of iodine was added. After 30 minutes of reaction, a mixed solution of 1 g (7 mmol) of ethyl 2-hydroxy-3-methyl-3-butenoate, 0.9 g (9 mmol) of triethylamine and 2 mL of chlorobenzene was added dropwise. After completion of the dropwise addition, the mixture was reacted at 60 DEG C for 1 hour. When the reaction rate was confirmed by GC, the desired ethyl 4-iodoseneethioate was 30% (mixture of E-isomer and Z-isomer).

^{1 H-NMR (400㎒, CDCl} 3) E sieve; δ: 6.00 (1H, s ), 4.21-4.13 (2H, m), 3.93 (2H, s), 2.32 (3H, s), 1.31-1.24 ( (2H, s), 4.21-4.13 (2H, m), 2.08 (3H, s), 1.31-1.24 (3H, m).

[Example 14] Preparation of ethyl 2-bromo-3-methyl-3-butenoate

2.8 g (9 mmol) of triphenyl phosphite was added to 10 mL of chlorobenzene, cooled to 5 캜 or lower, and 1.4 g (9 mmol) of bromine was added dropwise. After 30 minutes of reaction, a mixed solution of 1 g (7 mmol) of ethyl 2-hydroxy-3-methyl-3-butenoate, 0.9 g (9 mmol) of triethylamine and 2 mL of chlorobenzene was added dropwise. After completion of the dropwise addition, 20 mL of water was added, and the organic layer was separated and purified by silica gel column chromatography (ethyl acetate / hexane; 1/2) to obtain ethyl 2-bromo-3- 69% (mixture of E-isomer and Z-isomer).

^{1 H-NMR (400㎒, CDCl} 3) δ: 5.24 (1H, s), 5.10 (1H, s), 4.91 (1H, s), 4.24 (2H, q, J = 7.2㎐), 1.95 (3H, s), 1.30 (3H, t, J = 7.2 Hz).

[Example 15]

50 mg (0.2 mmol) of ethyl 2-bromo-3-methyl-3-butenoate and 155 mg (0.5 mmol) of TBAB were added to 1 mL of DMF and reacted at room temperature for 24 hours. When the reaction rate was confirmed by GC, the intended ethyl 4-bromoseneceinate was 95% (mixture of E-isomer and Z-isomer).

[Examples 16 and 17]

The reactions of Examples 16 and 17 were carried out in the same manner as in Example 15. Table 2 shows the halide, solvent, reaction temperature, reaction time, and reaction rate (%) of the target used in the examples.

[Comparative Example 1]

50 mg (0.2 mmol) of ethyl 2-bromo-3-methyl-3-butenoate was added to 1 mL of DMF, and the mixture was stirred at room temperature for 24 hours. The change was confirmed by GC, but ethyl 4-bromoseneceinate was not produced.

Claims (20)

In general formula (1):

(2), wherein the allyl alcohol derivative represented by the general formula (2): wherein R represents a protecting group, is reacted with a halogenating agent.

(Wherein R has the same meaning as defined above and X represents a halogen atom). The method according to claim 1, wherein the halogenating agent is at least one selected from the group consisting of a nitrogen-containing halogenating agent, a phosphorus-containing halogenating agent, and a sulfur-containing halogenating agent. The process according to claim 1, wherein the halogenating agent is a brominating agent and X is a bromine atom. 4. The method of claim 3 wherein the brominating agent is selected from the group consisting of bromine / triarylphosphine, N-bromosuccinimide / triarylphosphine, 1,3-dibromo-5,5-dimethylhydantoin / triarylphosphine, Bromine / phosphorous triaryl, N-bromosuccinic acid imide / triaryl phosphite, 1,3-dibromo-5,5-dimethylhydantoin / triaryl phosphorous acid, phosphorus tribromide, phosphorus pentabromide, phosphorus oxybromide And at least one phosphorus-containing brominating agent selected from the group consisting of phosphorus-containing brominating agents. 5. The process according to claim 4, wherein the triarylphosphine is triphenylphosphine, tri (p-tolyl) phosphine, tris (4-methoxyphenyl) phosphine or tris (4-chlorophenyl) phosphine. 6. The process according to claim 4 or 5, wherein the triarylphosphine is triphenylphosphine. 5. The method according to claim 4, wherein the triaryl phosphite is triphenyl phosphite, phosphorous tri (p-tolyl), or phosphorous tri (2,4-di-t-butylphenyl). 8. The process according to claim 4 or 7, wherein the triaryl phosphite is triphenyl phosphite or phosphorous acid tri (p-tolyl). 5. The process of claim 4 wherein the brominating agent is bromine / triphenylphosphine, N-bromosuccinimide / triphenylphosphine, 1,3-dibromo-5,5-dimethylhydantoin / triphenylphosphine, bromine / Triphenyl phosphite, N-bromosuccinic acid imide / triphenyl phosphite, 1,3-dibromo-5,5-dimethylhydantoin / triphenyl phosphite, bromine / phosphorous acid tri (p- (P-tolyl) or 1,3-dibromo-5,5-dimethylhydantoin / phosphorous acid tri (p-tolyl). The production method according to any one of claims 1 to 9, wherein the reaction is carried out in the presence of a base. 11. The process according to claim 10, wherein the base is an aromatic amine or an aliphatic amine. 12. The process according to claim 11, wherein the aromatic amine is pyridine. The method of claim 11, wherein the aliphatic amine is a tree (C ₁ ~C ₄ alkyl) amine, method. 14. The production method according to any one of claims 1 to 13, wherein the reaction is carried out in the presence of a halide. 15. The process according to claim 14, wherein the halide is a halide of lithium, sodium or potassium. 15. The process according to claim 14, wherein the halide is a halide of quaternary ammonium. 17. The process according to claim 16, wherein the halide of the quaternary ammonium is tetra (C ₁ -C ₄ alkyl) ammonium halide. In general formula (1):

(3), wherein the allyl alcohol derivative represented by the general formula (3): (wherein R represents a protecting group) is reacted with a halogenating agent at a temperature of 10 ° C or lower.

(Wherein R has the same meaning as defined above and X represents a halogen atom). The general formula (3)

(2), wherein the allyl halide derivative represented by the general formula (2): wherein R represents a protecting group and X represents a halogen atom, is reacted with a halide at a temperature higher than 10 ° C.

(Wherein R and X have the same meanings as defined above). The production method according to claim 19, wherein the allyl halide derivative represented by the general formula (3) is obtained by the production method according to claim 18.