WO2006075596A1 - Procede servant a produire un compose acide 2-allylcarboxylique - Google Patents

Procede servant a produire un compose acide 2-allylcarboxylique Download PDF

Info

Publication number
WO2006075596A1
WO2006075596A1 PCT/JP2006/300183 JP2006300183W WO2006075596A1 WO 2006075596 A1 WO2006075596 A1 WO 2006075596A1 JP 2006300183 W JP2006300183 W JP 2006300183W WO 2006075596 A1 WO2006075596 A1 WO 2006075596A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
bond
chemical
group
Prior art date
Application number
PCT/JP2006/300183
Other languages
English (en)
Japanese (ja)
Inventor
Hideki Matsuda
Makoto Nakazawa
Koichi Kanehira
Original Assignee
Kuraray Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kuraray Co., Ltd. filed Critical Kuraray Co., Ltd.
Priority to JP2006552923A priority Critical patent/JPWO2006075596A1/ja
Publication of WO2006075596A1 publication Critical patent/WO2006075596A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
    • C07C47/21—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation

Definitions

  • the present invention relates to a method for producing a 2-arylcarboxylic acid compound.
  • a 2-arylcarboxylic acid compound obtained by the present invention such as 2-aryloctanoic acid, is an (R) -2-propyloctanoic acid useful as a therapeutic or preventive agent for neurodegenerative diseases caused by abnormal function of astrocytes. It is useful as a synthetic intermediate (see WO99Z058513 pamphlet).
  • a method for producing a 2-arylcarboxylic acid compound for example, 2-aryloctanoic acid
  • (1) a method of reacting octanoic acid and allylpromide in the presence of a basic substance see Non-Patent Document 1)
  • (2) a method in which malonic acid diester and allylpromide are reacted in the presence of a base, and further hexylpromide is reacted, followed by hydrolysis and decarboxylation see Non-Patent Document 2.
  • Non-Patent Document 1 Journal of the Chemical Society, Perkin Transactions 1 (1998), p. 1373- 1382
  • Non-Patent Document 2 Chemical & Pharmaceutical Bulletin, 1976, No. 24, No. 3, p. 538-540 Disclosure of the Invention
  • an object of the present invention is to solve the above problems and to use 2-arylcarboxylic acid compound.
  • the object is to provide a method which can be produced industrially advantageously in a yield, and a novel synthetic intermediate therefor.
  • a bond having a solid line and a dotted line force represents a single bond or a double bond
  • X is a formyl group
  • a bond consisting of a solid line and a dotted line represents a single bond or a double bond
  • X is a formyl group or the above dialkoxymethyl group
  • Y represents a hydrogen atom
  • X is the above trialkoxymethyl group.
  • ⁇ represents an alkoxy group represented by the formula (wherein represents an alkyl group or an aryl group having a carbon number to)
  • —arylcarbonyl compound (hereinafter referred to as “)” is represented by the following formula: [0011]
  • a 2-arylcarbonyl compound [hereinafter referred to as 2-arylcarbonyl compound (II-1)] is obtained. Then, the 2-arylcarbonyl compound (II 1) is oxidized, The method for producing a 2-arylcarboxylic acid compound (III) according to 1);
  • the 2-arylcarboxylic acid compound can be produced industrially advantageously in good yield.
  • Powerful 2-arylcarboxylic acid compounds such as 2-aryloctanoic acid are useful as therapeutic or preventive agents for neurodegenerative diseases caused by astrocyte dysfunction (R ) —Useful as an intermediate for the synthesis of 2-propyloctanoic acid.
  • X in the compound (I) is a formyl group, a dialkoxymethyl group represented by the formula CH (OR 1 ), or
  • X is a formyl group or di
  • Y of the arylcarbonyl compound ( ⁇ ) is a hydrogen atom, and the conversion to the arylcarbonyl compound ( ⁇ ) force to the arylcarboxylic acid compound (III) is performed by an oxidation reaction.
  • X is a trialkoxymethyl group
  • Y is an alkoxy group represented by the formula —OR 2 , and the conversion to the arylcarbonyl compound ( ⁇ ) force to the arylcarboxylic acid compound (III) is carried out by a hydrolysis reaction. .
  • Examples of the alkyl group having 16 carbon atoms represented by R 1 and R 2 include, for example, methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, tert-butyl group, n Examples include pentyl group, isopentyl group, neopentyl group, n-xyl group, cyclopropyl group, cyclobutyl group, cyclopentyl group, and cyclohexyl group.
  • compound (I) is compound (1-1)
  • Y of 2-arylcarbonyl compound ( ⁇ ) is a hydrogen atom
  • 2-arylcarbonyl compound ( ⁇ ) is 2 —Arylcarbonyl compound ( ⁇ —1).
  • reaction step 1 a step in which compound (1-1) is reacted in the presence of an acid catalyst and allylic alcohol to obtain 2-arylcarbonyl compound ( ⁇ -1).
  • Reaction step 1 includes a reaction (hereinafter referred to as “reaction A”) in which a compound (1-1) and a allylic alcohol are also obtained in the presence of an acid catalyst (hereinafter referred to as “reaction A”), a dialylacetal compound Via a reaction (hereinafter referred to as “Reaction B”) in which (IV) is dearylated alcohol, followed by Claisen rearrangement to give 2-arylcarbonyl compound (II 1) It is a process. First, reaction A will be described.
  • the acid catalyst used in Reaction A for example, inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid; strong acids such as acetic acid, succinic acid, maleic acid, benzoic acid, terephthalic acid, and trifluoroacetic acid; rubonic acid; methane Examples thereof include sulfonic acids such as sulfonic acid, toluenesulfonic acid, and trifluoromethanesulfonic acid; acidic salts such as pyridine and toluenesulfonic acid; acidic ion-exchange resin.
  • inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid
  • strong acids such as acetic acid, succinic acid, maleic acid, benzoic acid, terephthalic acid, and trifluoroacetic acid
  • rubonic acid methane Examples thereof include sulfonic acids such as sulfonic acid, toluenesulfonic acid, and tri
  • Carbonic acid is preferably used, and maleic acid is particularly preferably used.
  • the amount of the acid catalyst to be used is not particularly limited, but is usually from 0.000001 to 1 mol based on 1 mol of the compound (1-1), from an economical viewpoint, it is preferably 0.001.
  • the range of -0.5 mol is more preferred.
  • the range of 0.001-0. 1 mol is more preferred.
  • the amount of allylic alcohol used in reaction A is preferably in the range of 0.1 to 50 mol per mol of compound (I 1), and is preferably in the range of 0.2 to 20 mol. Is more preferably in the range of 0.5 to 10 moles.
  • Reaction A can be carried out in the presence or absence of a solvent.
  • Solvents that can be used are not particularly limited as long as they do not adversely affect the reaction.For example, aromatic hydrocarbons such as toluene, xylene, and mesitylene; aliphatic hydrocarbons such as hexane, heptane, and octane; dichloroethane, black benzene And halogenated hydrocarbons such as diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, diglyme, triglyme and the like.
  • the amount used is not particularly limited, but it is usually preferable that the amount is in the range of 0.1 to 10 times the mass of the compound (I 1), and easy post-treatment. From this viewpoint, the range of 0.2 to 5 times the mass is more preferable.
  • the reaction temperature of the reaction A is usually in the range of 20 to 120 ° C, and from the viewpoint of the reaction rate, the selectivity of the reaction and the stability of the diallyl acetal compound (IV), 80 to 120 ° C. A range of C is preferred.
  • the reaction pressure is not particularly limited, but is usually in the range of 0.1 to 500 kPa, preferably in the range of 1 to 200 kPa.
  • the reaction time varies depending on the type and amount of the acid catalyst used, the reaction temperature, the reaction pressure, etc., but is usually in the range of 30 minutes to 40 hours.
  • the method for carrying out reaction A is not particularly limited.
  • compound (I 1), aryl alcohol, an acid catalyst and, if necessary, a solvent are mixed and reacted at a predetermined temperature and a predetermined pressure. It can be implemented from Sako.
  • the reaction may be carried out while removing powerful water.
  • the method for removing water is not particularly limited.
  • a dehydrating agent that does not adversely affect the reaction such as molecular sieves is added to the reaction system, or the reaction with the solvent in the reaction system is carried out.
  • the method of distilling by boiling and the like can be mentioned.
  • the thus obtained diallyl acetal compound (IV) can also be separated and purified by the reaction mixture force by a method generally used in the separation and purification method of organic compounds. For example, it can be purified by adding water to the reaction mixture, removing the acid catalyst to the aqueous layer, separating and obtaining the organic layer, and distilling the organic layer.
  • the reaction mixture obtained in the above reaction A can be used as it is in the following reaction B described later without separation and purification, and in obtaining a 2-arylcarbonyl compound ( ⁇ -1). This is a more preferable and simple method.
  • 1,1-Diaryloxy-7-otaten is a novel compound.
  • the acid catalyst used in the reaction B is not particularly limited, and examples thereof include the same acid catalysts used in the reaction A described above. Among these, carboxylic acid is preferably used from the viewpoints of easy availability and influence on the reaction apparatus, and maleic acid is particularly preferable.
  • the amount of the acid catalyst used is not particularly limited, but is usually in the range of 0.0001 to 1 mol per mol of diallyl acetal compound (IV). The range of 0001 to 0.5 mol is more preferable. The range of 0.0005-0. 1 mol is more preferable.
  • the diallyl acetal compound (IV) obtained in Reaction A is separated from the reaction mixture and purified. Without being added to the reaction B (preferred embodiment for carrying out the present invention), since the acid catalyst is already present in the reaction system, there is no particular need to add it. There is no problem.
  • Reaction B can be carried out in the presence or absence of a solvent.
  • the powerful solvent include the same solvents as those that can be used in Reaction A, as long as they do not adversely affect the reaction.
  • the amount used is not particularly limited, but usually it is preferably in the range of 0.1 to 10 times the mass with respect to the diarylacetal compound (IV).
  • the diallyl acetal compound (IV) obtained in the reaction A is subjected to the reaction B without being separated and purified from the reaction mixture (preferred embodiment for carrying out the present invention).
  • the solvent may already be present in the reaction mixture, it is not particularly necessary to add it further, but it may be added if necessary.
  • the reaction pressure in the reaction B is preferably in the range of 0.1 to 500 kPa, more preferably in the range of 1 to 50 kPa, from the viewpoint of allowing the reaction to proceed smoothly.
  • the reaction temperature is preferably in the range of 120 to 180 ° C, more preferably in the range of 130 to 170 ° C.
  • the reaction time varies depending on the type of acid catalyst, amount used, reaction temperature, reaction pressure, and the like. Usually, the reaction time is in the range of 30 minutes to 48 hours.
  • the method for carrying out reaction B is not particularly limited.
  • the diaryl acetal compound (IV) when the diaryl acetal compound (IV) is separated and purified, the diaryl acetal compound (IV), an acid catalyst and It can be carried out by mixing the solvent as necessary and reacting at a predetermined temperature and pressure.
  • reaction condition If the reaction temperature and reaction pressure are set to the predetermined values in reaction B, the reaction A can be transferred to the reaction B.
  • Reaction B from the viewpoint of yield, it is preferable to carry out the reaction while removing the by-produced aryl alcohol as the reaction proceeds, and the resulting 2-arylcarbonyl compound is also produced.
  • the separation and purification of the 2-arylcarbolyl compound ( ⁇ -1) from the reaction mixture thus obtained can be carried out by a method generally used in the separation and purification of organic compounds. For example, after adding a solvent and water to the obtained reaction mixture, the aqueous layer is removed, the solvent is appropriately distilled off from the organic layer, and the residue can be further distilled. Further, the residue can be directly subjected to the oxidation reaction described later without purification.
  • reaction step 2 a step of oxidizing the 2-arylcarbonyl-compound ( ⁇ -1) obtained by the above method to obtain a 2-arylcarboxylic acid compound (III) (hereinafter referred to as "reaction step 2"). Will be described).
  • an oxidizing agent generally used for converting aldehydes to carboxylic acids can be used.
  • strong oxidizing agents include oxygen; peroxyhydrogen; organic peracid compounds such as formic acid, peracetic acid, m-peroxybenzoic acid; sodium chlorite, sodium bromate
  • Metal halide salts such as potassium chlorite and potassium bromite
  • metal hypohalite salts such as sodium hypochlorite, sodium hypobromite, potassium hypochlorite and potassium hypobromite
  • Halogenate metal salts such as sodium chlorate, sodium bromate, potassium chlorate and potassium bromate
  • permanganate metal salts such as sodium permanganate and potassium permanganate
  • acid chrome silver oxide
  • silver oxide examples thereof include metal oxides such as ruthenium oxide.
  • reaction step 2 As an example of the reaction step 2, a case where a metal halous acid salt is used as an oxidizing agent will be described.
  • the metal halous acid salt is from the viewpoint of availability.
  • Sodium chlorite is preferably used.
  • the amount of metal phosphite or metal salt of rogenic acid it is usually preferred to be in the range of 0.1 to 20 moles per mole of 2-arylcarbonyl compound ( ⁇ -1). More preferably, it is in the range of 0.5 to 10 mol, and more preferably in the range of 0.8 to 5 mol.
  • a halogen scavenger When the reaction step 2 is performed using a metal halous acid salt, it is preferable to add a halogen scavenger to the reaction system in order to suppress a halogenation reaction as a side reaction.
  • the halogen scavenger include resorcinol, 2-methyl 2-butene, dimethyl sulfoxide and the like.
  • the amount used is not particularly limited, but it is usually in the range of 0.1 to 50 mol with respect to 1 mol of the diarylcarbol compound (11-1). A preferred range is 0.5 to 20 moles, and a more preferred range is 0.8 to 10 moles.
  • Reaction step 2 is preferably performed in the presence of a solvent.
  • the solvent is not particularly limited as long as it does not adversely affect the reaction, for example, aromatic hydrocarbons such as toluene, xylene, mesitylene, etc .; aliphatic hydrocarbons such as hexane, heptane, octane; dichloroethane, black benzene, etc.
  • alcohols such as methanol, ethanol, isopropanol, and t-butanol
  • ethers such as diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, diglyme (diethylene glycol dimethyl ether) and triglyme (triethylene glycol dimethyl
  • the amount of solvent used it is usually preferred that the amount is in the range of 0.1 to 100 times the mass of 2-arylcarbonyl compound (II-1). From the viewpoint of simplicity, the range of 0.2 to 50 times mass is more preferable, and the range of 0.5 to 30 times mass is more preferable.
  • Reaction step 2 is preferably carried out under acidic conditions, more preferably in the range of pH 2-6.
  • an acidic compound such as phosphoric acid, sodium dihydrogen phosphate, potassium dihydrogen phosphate into the reaction system.
  • an acidic compound such as phosphoric acid, sodium dihydrogen phosphate, potassium dihydrogen phosphate
  • 2-aryl carbo-louis compound (11-1) 1 It is preferably in the range of 0.1 to 20 mol, more preferably in the range of 0.5 to 10 mol, and even more preferably in the range of 0.8 to 5 mol. preferable.
  • the reaction temperature is preferably in the range of 0 to 100 ° C, in view of the reaction rate, the selectivity of the reaction, and the stability of the target product, in the range of 10 to 70 ° C. Is more preferable.
  • the reaction pressure is preferably in the range of 0.1 to 500 kPa, more preferably in the range of 1 to 200 kPa.
  • the reaction time varies depending on the type and amount of metal halite (oxidizer), halogen scavenger, acidic compound, type and amount of solvent, reaction temperature, reaction pressure, etc. ⁇ 24 hours range.
  • the method for carrying out the reaction step 2 is not particularly limited.
  • a 2-arylcarbonyl compound (II 1), an oxidizing agent, a solvent, and optionally a halogen scavenger and Z or an acidic compound are mixed,
  • the reaction can be carried out at a temperature and under a predetermined pressure.
  • the separation and purification of the diarylcarboxylic acid compound ( ⁇ ) from the reaction mixture thus obtained can be carried out by a method generally used in the separation and purification of organic compounds.
  • a basic compound such as sodium hydroxide and potassium hydroxide is added to the reaction mixture to make it basic, and then concentrated, and water and an organic solvent such as hexane, toluene, diisopropyl ether are added.
  • the organic layer and the aqueous layer are separated, and the aqueous layer is acidified with dilute hydrochloric acid or the like and then extracted with the organic solvent described above.
  • the extract is concentrated and further distilled to obtain a high purity 2-
  • a arylcarboxylic acid compound ( ⁇ ) can be obtained.
  • 2-aryl-7-otatenic acid is a novel compound.
  • compound (I) is compound (I 2)
  • Y of 2-arylcarbonyl compound ( ⁇ ⁇ ) is a hydrogen atom
  • 2-arylcarbonyl compound ( ⁇ ) is 2 —Arylcarbonyl compound (II-1).
  • reaction step ⁇ 2-arylcarbonyl compound ( ⁇ -1)
  • the acid catalyst used in the reaction step ⁇ there are no particular restrictions on the acid catalyst used in the reaction step ⁇ , and the same catalysts as those used in the reaction A in the above-mentioned reaction step 1 can be mentioned. Among them, viewpoints such as availability and influence on the reaction apparatus It is preferable to use carboxylic acid, and it is particularly preferable to use maleic acid.
  • the amount of the acid catalyst to be used is not particularly limited, but it is usually from an economical viewpoint that it is preferably in the range of 0.0001-0. 5 mol with respect to 1 mol of the compound (1-2). A force in the range of 0.001 to 0.1 mol is preferred, and a range of 0.0005 to 0.05 mol is more preferred.
  • the amount of allylic alcohol used in the reaction step ⁇ is preferably in the range of 0.1 to 20 moles relative to 1 mole of compound (I 2), in the range of 0.2 to 10 moles. More preferably, it is more preferably in the range of 0.5 to 5 moles.
  • the reaction step ⁇ can be performed in the presence or absence of a solvent.
  • solvents are not particularly limited as long as they do not adversely affect the reaction, for example, aromatic hydrocarbons such as toluene, xylene and mesitylene; aliphatic hydrocarbons such as hexane, heptane and octane; dichloroethane and black benzene And halogenated hydrocarbons such as diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, diglyme (diethylene glycol dimethyl ether), and ethers such as triglyme (triethylene glycol dimethyl ether).
  • the amount used is not particularly limited. Generally, it is preferable that the amount is in the range of 0.1 to 10 times the mass of the compound (I 2). From the viewpoint, it is more preferably in the range of 0.2 to 5 times mass.
  • the reaction pressure in the reaction step ⁇ is preferably in the range of 0.1 to 500 kPa, more preferably in the range of 1 to 200 kPa, from the viewpoint of allowing the reaction to proceed smoothly.
  • the reaction temperature is preferably in the range of 120 to 200 ° C, more preferably in the range of 130 to 180 ° C. preferable.
  • the reaction time varies depending on the type of acid catalyst, amount used, reaction temperature, reaction pressure, etc. Usually, it is in the range of 30 minutes to 48 hours.
  • the method for carrying out the reaction step ⁇ is not particularly limited.
  • the compound (I 2), an acid catalyst and a solvent as necessary are mixed, and aryl alcohol is added dropwise at a predetermined temperature and a predetermined pressure. It can be carried out by reacting.
  • the reaction step 1 from the viewpoint of the yield of the 2-arylcarbonyl compound ( ⁇ -1), the formula I ⁇ OH generated as a by-product as the reaction proceeds (wherein R 1 is as defined above)
  • the reaction may be carried out while distilling off the alcohol indicated by It is also possible to carry out the reaction while distilling the produced 2-arylcarbonyl compound ( ⁇ -1).
  • Separation and purification of the 2-arylcarbonyl compound (II-1) from the reaction mixture containing the 2-arylcarbonyl compound ( ⁇ -1) thus obtained is generally performed in the separation and purification of organic compounds. It can be implemented by the method used. For example, after adding a solvent and water to the obtained reaction mixture, the aqueous layer is removed, and the residue obtained by appropriately distilling off the solvent from the obtained organic layer can be purified by further distillation. In addition, the organic layer can be directly subjected to an acid-acid reaction described later.
  • a step of obtaining a 2-arylcarboxylic acid compound ( ⁇ ) by acidifying the 2-arylcarboxyl compound (II-1) obtained by the above method (hereinafter referred to as reaction step 2, and 1) is the same as Reaction Step 2 in the case where X is a formyl group.
  • the production method of the compound (I 2) which is a raw material of the present invention, is not particularly limited. And trimethyl orthoacetate are reacted and then neutralized, and the low boiling point compound is distilled off.
  • the compound (I2) with higher purity can be obtained by appropriately applying a usual method for separating and purifying organic compounds such as distillation.
  • the compound (I) is the compound (1-3)
  • Y of the 2- arylcarbonyl compound ( ⁇ ) is represented by the formula —OR 2 (wherein R 2 is as defined above)
  • the 2-arylcarbonyl compound (II) is an arylcarbonyl compound (II 2).
  • reaction step 1 ⁇ the step of obtaining the 2-arylcarbonyl compound (II 2) by reacting the compound (1-3) in the presence of an acid catalyst and allylic alcohol (hereinafter referred to as reaction step 1 ⁇ ) will be described. To do.
  • the acid catalyst used in reaction step 1 there are no particular restrictions on the acid catalyst used in reaction step 1 to, and examples thereof include the same ones used in reaction A in reaction step 1 described above. Of these, viewpoints such as availability, influence on the reaction apparatus, etc. It is preferable to use carboxylic acid, and maleic acid is particularly preferable.
  • the amount of the acid catalyst to be used is not particularly limited, but is usually in the range of 0.00001-0. 5 mol with respect to 1 mol of the compound (1-3). A force in the range of 0001 to 0.1 mol is preferred, and a range of 0.0005 to 0.05 mol is more preferred.
  • the amount of allylic alcohol used in the reaction step ⁇ is preferably in the range of 0.1 to 20 mol per mol of compound (I 3), and in the range of 0.2 to 10 mol. More preferably, it is more preferably in the range of 0.5 to 5 moles.
  • the reaction step ⁇ can be carried out in the presence or absence of a solvent.
  • solvents are not particularly limited as long as they do not adversely affect the reaction, for example, aromatic hydrocarbons such as toluene, xylene and mesitylene; aliphatic hydrocarbons such as hexane, heptane and octane; dichloroethane and black benzene And halogenated hydrocarbons such as diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, diglyme (diethylene glycol dimethyl ether), and ethers such as triglyme (triethylene glycol dimethyl ether).
  • the amount used is not particularly limited. Generally, it is preferable that the amount is in the range of 0.1 to 10 times the mass of the compound (I 3). From the viewpoint, it is more preferably in the range of 0.2 to 5 times mass.
  • the reaction pressure at ⁇ is preferably in the range of 0.1 to 50 OkPa, more preferably in the range of 1 to 200 kPa, from the viewpoint of allowing the reaction to proceed smoothly.
  • the reaction temperature is preferably in the range of 120 to 200 ° C, more preferably in the range of 130 to 180 ° C.
  • the reaction time varies depending on the type and amount of acid catalyst used, reaction temperature, reaction pressure, etc., but is usually in the range of 30 minutes to 48 hours.
  • the method for carrying out the reaction steps 1 to is not particularly limited. For example, the compound (I 3), an acid catalyst and a solvent as necessary are mixed, and allylic alcohol is added dropwise at a predetermined temperature and a predetermined pressure. It can be carried out by reacting.
  • reaction step 1 ⁇ from the viewpoint of the yield of 2-aryl carbo-louis compound ( ⁇ -2), by-product as the reaction proceeds, the formula I ⁇ OH (wherein R 1 is as defined above).
  • the reaction may be carried out while removing the alcohol represented by). It is also possible to carry out the reaction while distilling the generated 2-aryl carbo-louis compound ( ⁇ -2).
  • Separation and purification of the biarylcarbo-Louis compound ( ⁇ -2) from the reaction mixture thus obtained can be carried out by a method generally used in separation and purification of organic compounds. For example, after adding a solvent and water to the obtained reaction mixture, the aqueous layer is removed, and the residue obtained by distilling off the solvent as appropriate from the obtained organic layer can be further purified. In addition, the organic layer or the reaction mixture is not purified, but can be directly subjected to the hydrolysis reaction described later.
  • reaction step 2 the 2-arylcarbonyl compound ( ⁇ -2) obtained by the above method is hydrolyzed to obtain 2-arylcarboxylic acid compound (III) (hereinafter referred to as reaction step 2 "). ) Will be explained.
  • Examples of basic compounds include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; carbonates such as sodium carbonate and potassium carbonate; sodium hydrogen carbonate and potassium hydrogen carbonate And hydrogen carbonates.
  • the amount of the basic compound used is usually in the range of 0.1 to 20 mol with respect to 1 mol of 2-arylcarbol compound ( ⁇ -2). More preferably, it is in the range of 0.5 to 10 mol, more preferably in the range of 0.8 to 5 mol.
  • the amount of water used is usually 0. 1 mol of 2-arylcarbonyl compound ( ⁇ -2).
  • the range of 1 to 50 mol is preferred.
  • Reaction steps 2 to are preferably performed in the presence of a solvent.
  • Solvents that can be used are not particularly limited as long as they do not adversely affect the reaction.For example, aromatic hydrocarbons such as toluene, xylene, and mesitylene; aliphatic hydrocarbons such as hexane, heptane, and octane; dichloroethane, black benzene, etc.
  • Halogenated hydrocarbons such as methanol, ethanol, isopropanol, and t-butanol; ethers such as diisopropyl ether, dibutyl ether, tetrahydrofuran, dioxane, diglyme, and triglyme; -tolyl compounds such as acetonitrile, benzo-tolyl, and the like; Examples include amido compounds such as formamide and dimethylacetamide. Among these, it is preferable to use alcohol. Although there is no particular limitation on the amount of solvent used, it is usually preferred that the 2-allylcarbonyl compound (II-2) is in the range of 0.1 to LOO times mass. From the viewpoint of simplicity, the range of 0.2 to 20 times mass is more preferable, and the range of 0.5 to 10 times mass is more preferable.
  • the reaction temperature in the reaction steps 2 to is preferably in the range of 0 to 150 ° C.
  • the reaction pressure is in the range of 0.1 to 500 kPa, and more preferably in the range of 1 to 200 kPa.
  • the reaction time varies depending on the type and amount of the basic compound used, the amount of water used, the reaction temperature, the reaction pressure, etc., but is usually in the range of 10 minutes to 24 hours.
  • the method for carrying out reaction steps 2 to is not particularly limited, for example, 2-arylcarbonyl compound (II 2) or 2-arylcarbonyl compound (II-) obtained by post-treatment of reaction step ⁇ '. It can be carried out by mixing an organic layer containing 2), a basic compound, water and preferably a solvent and reacting them under a predetermined temperature and a predetermined pressure.
  • the separation and purification of the diarylcarboxylic acid compound ( ⁇ ) from the reaction mixture thus obtained can be carried out by a method generally used in the separation and purification of organic compounds. For example, after concentrating the reaction mixture, water and an organic solvent are added and mixed, and then the aqueous layer is taken out. The aqueous layer is acidified with dilute hydrochloric acid and then with an organic solvent such as hexane, toluene, and diisopropyl ether. By extracting and distilling a powerful extract, A highly pure 2-arylcarboxylic acid compound ( ⁇ ) can be obtained.
  • the production method of the compound (I 3) which is a raw material of the present invention is not particularly limited.
  • octane-tolyl or otaten-tolyl is added in the presence of a solvent such as diisopropyl ether and a salt of hydrogen and a compound.
  • Reaction with an alcohol represented by I ⁇ OH (wherein R 1 is as defined above) at 5-20 ° C for 5-24 hours the precipitated solid is filtered, and the resulting solid is filtered.
  • it can be produced by reacting with an alcohol represented by the formula I ⁇ OH (R 1 is as defined above) in the presence of a solvent such as diisopropyl ether at 20-30 ° C for 5-24 hours. .
  • the organic layer was washed with 100 ml of 5% by mass aqueous sodium hydrogen carbonate solution and then with 100 ml of saturated brine, and then concentrated to obtain 106.8 g of a crude product.
  • the obtained crude product was subjected to gas chromatography [analytical instrument: GC-9A, manufactured by Shimadzu Corporation, column used: G-230 (1. D .: 1.2 mm, Column length: 20 m, membrane thickness: 1.0 m), analysis condition: injection temp. 280 ° C, temperature rise condition: 80 ° C ⁇ (temperature rise in 10 ° CZ minutes) ⁇ 250 ° C (20 minutes) As a result, it was found to contain 1,1-diallyloxyoctane 84. Og (yield 74% based on otatanal).
  • the organic layer was washed with 100 ml of 5% by mass aqueous sodium hydrogen carbonate solution and then with 100 ml of saturated brine, and then concentrated to obtain 105.8 g of a crude product.
  • the obtained crude product was distilled under reduced pressure (116 ° CZ0.7 kPa) to obtain 88.2 g (purity 98.1%, yield 77%) of 1,1 diallyloxy-7-octene having the following physical properties. It was.
  • the solution was dropped into the flask over a period of minutes. After completion of the dropwise addition, the mixture was stirred at 25 ° C for 2 hours.
  • the obtained reaction mixture was adjusted to pHIO or higher by adding 20 mass% aqueous sodium hydroxide solution, concentrated, added with 100 ml of water, washed twice with 100 ml of toluene, and the organic layer was separated. Concentrated hydrochloric acid was added to the aqueous layer, the pH of the aqueous layer was adjusted to 3 or less, and then extracted twice with 50 ml of toluene. The resulting extract was concentrated to obtain 18.9 g of a crude product. The obtained crude product was distilled under reduced pressure (142 ° C / 0.5 kPa) to obtain 15.1 g (purity 99.5%, yield 91%) of 2-aryl 7-otatenic acid having the following physical properties. It was.
  • the pH of the reaction mixture was adjusted to 10 or more by adding 20 mass% aqueous sodium hydroxide solution.
  • the obtained reaction mixture was concentrated, 30 ml of water was added, and the mixture was washed twice with 30 ml of toluene to separate and remove the organic layer.
  • Hydrochloric acid was added to the aqueous layer, and the pH of the aqueous layer was adjusted to 3 or less, followed by extraction twice with 15 ml of toluene, and the resulting extract was concentrated to obtain 6.6 g of a crude product.
  • the obtained crude product was distilled under reduced pressure (138 ° CZ0.5 kPa) to obtain 5.5 g of 2-aryloctanoic acid (purity 99.1%, yield 91%).
  • the precipitated solid was filtered, washed with diisopropyl ether, and then dried under reduced pressure to obtain 21. lg of white solid.
  • 21. lg of the white solid obtained in the above operation 21. lg of the white solid obtained in the above operation, 20.9 g of methanol and 97 ml of diisopropyl ether were placed and stirred at 25 ° C. for 20 hours.
  • the precipitated salt ammonium was filtered off, and the filtrate was concentrated under reduced pressure to obtain 23. lg of a crude product. This crude product was distilled under reduced pressure (86 ° CZ 0.3 kPa) to obtain 19.7 g of trimethyl orthooctanoate (purity 99.9%, yield 51% based on octane-tolyl).
  • Concentrated hydrochloric acid is added to the remaining aqueous layer to adjust the pH of the aqueous layer to 3 or less, followed by extraction twice with 20 ml of toluene. The obtained extract and the previous organic layer are combined and concentrated under reduced pressure. 8.5 g of crude product was obtained. This crude product was distilled under reduced pressure (138 ° CZ0.5 kPa) to obtain 6.8 g of 2-aryloctanoic acid (purity 99.0%, yield 97%).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Il est exposé un procédé servant à produire de façon industriellement avantageuse un acide 2-allylcarboxylique avec un rendement de production élevé. Il est précisément exposé un procédé servant à produire un composé acide 2-allylcarboxylique lequel est caractérisé en ce qu'on fait réagir un composé représenté par la formule (I) en présence d'un catalyseur acide et d'un alcool allylique, ce par quoi on obtient un composé 2-allylcarbonyle représenté par la formule (II), et en ce qu'on convertit ensuite le composé 2-allylcarbonyle ainsi obtenu en un acide 2-allylcarboxylique représenté par la formule (III). (Dans ces formules, les liaisons représentées par une ligne continue et une ligne pointillée représentent une liaison simple ou une double liaison ; X représente un groupe formyle, un groupe dialcoxyméthyle ou un groupe trialcoxyméthyle ; et Y représente un atome d'hydrogène ou un groupe alcoxy.)
PCT/JP2006/300183 2005-01-13 2006-01-11 Procede servant a produire un compose acide 2-allylcarboxylique WO2006075596A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2006552923A JPWO2006075596A1 (ja) 2005-01-13 2006-01-11 ２−アリルカルボン酸化合物の製造方法

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
JP2005-006705 2005-01-13
JP2005006705 2005-01-13
JP2005115025 2005-04-12
JP2005-115025 2005-04-12
JP2005-244028 2005-08-25
JP2005244028 2005-08-25
JP2005295492 2005-10-07
JP2005-295492 2005-10-07

Publications (1)

Publication Number Publication Date
WO2006075596A1 true WO2006075596A1 (fr) 2006-07-20

Family

ID=36677621

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/300183 WO2006075596A1 (fr) 2005-01-13 2006-01-11 Procede servant a produire un compose acide 2-allylcarboxylique

Country Status (2)

Country Link
JP (1) JPWO2006075596A1 (fr)
WO (1) WO2006075596A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102675166A (zh) * 2012-05-11 2012-09-19 山东齐都药业有限公司 用于制备2-丙基庚酸的新中间体、其制备方法及2-丙基庚酸的制备方法
WO2012169475A1 (fr) * 2011-06-08 2012-12-13 第一三共株式会社 Procédé pour produire un composé bicyclique via réarrangement de claisen
JP2014208698A (ja) * 2007-04-11 2014-11-06 第一三共株式会社 ノイラミン酸誘導体の製造方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3907718A (en) * 1974-07-22 1975-09-23 Int Flavors & Fragrances Inc 2-Methyl-4-pentenoic acid ester fragrance
US3976801A (en) * 1972-07-22 1976-08-24 International Flavors & Fragrances Inc. Flavoring compositions containing alkyl esters of 2-methyl-4-pentenoic acid
US4307252A (en) * 1978-10-13 1981-12-22 Ruhrchemie Aktiengesellschaft 2-Propyl-pent-4-en-1-al
JPH07316092A (ja) * 1993-06-01 1995-12-05 Ono Pharmaceut Co Ltd ペンタン酸誘導体、その製造方法およびそれらを含有する薬剤
WO1999058513A1 (fr) * 1998-05-12 1999-11-18 Ono Pharmaceutical Co., Ltd. Nouveaux intermediaires et procedes de preparation de derives d'acide octanoique optiquement actif
WO2000048982A1 (fr) * 1999-02-18 2000-08-24 Ono Pharmaceutical Co., Ltd. Procede de preparation d'acide (2r)-2-propyloctanoique

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3976801A (en) * 1972-07-22 1976-08-24 International Flavors & Fragrances Inc. Flavoring compositions containing alkyl esters of 2-methyl-4-pentenoic acid
US3907718A (en) * 1974-07-22 1975-09-23 Int Flavors & Fragrances Inc 2-Methyl-4-pentenoic acid ester fragrance
US4307252A (en) * 1978-10-13 1981-12-22 Ruhrchemie Aktiengesellschaft 2-Propyl-pent-4-en-1-al
JPH07316092A (ja) * 1993-06-01 1995-12-05 Ono Pharmaceut Co Ltd ペンタン酸誘導体、その製造方法およびそれらを含有する薬剤
WO1999058513A1 (fr) * 1998-05-12 1999-11-18 Ono Pharmaceutical Co., Ltd. Nouveaux intermediaires et procedes de preparation de derives d'acide octanoique optiquement actif
WO2000048982A1 (fr) * 1999-02-18 2000-08-24 Ono Pharmaceutical Co., Ltd. Procede de preparation d'acide (2r)-2-propyloctanoique

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KABUSHIKI KAISHA TOKYO KAGAKU DOJIN: "McMurry Yuki Kagaku (Chu),", KABUSHIKI KAISHA TOKYO KAGAKU DOJIN, XX, XX, no. ED. 4, 1 January 1998 (1998-01-01), XX, pages 747 - 749, XP002999580 *
TAMAO K. ET AL.: "Synthetic Applications of Functionalized Silyl Anions: Aminosilyl Anions as Hydroxy Anion Equivalent", TETRAHEDRON, vol. 52, no. 16, 1996, pages 5765 - 5772, XP004104143 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014208698A (ja) * 2007-04-11 2014-11-06 第一三共株式会社 ノイラミン酸誘導体の製造方法
WO2012169475A1 (fr) * 2011-06-08 2012-12-13 第一三共株式会社 Procédé pour produire un composé bicyclique via réarrangement de claisen
EP2719677A4 (fr) * 2011-06-08 2014-12-03 Daiichi Sankyo Co Ltd Procédé pour produire un composé bicyclique via réarrangement de claisen
JPWO2012169475A1 (ja) * 2011-06-08 2015-02-23 第一三共株式会社 クライゼン転位反応による二環性化合物の製造方法
US9162971B2 (en) 2011-06-08 2015-10-20 Daiichi Sankyo Company, Limited Methods for producing bicyclic compounds via claisen rearrangements
CN102675166A (zh) * 2012-05-11 2012-09-19 山东齐都药业有限公司 用于制备2-丙基庚酸的新中间体、其制备方法及2-丙基庚酸的制备方法
CN102675166B (zh) * 2012-05-11 2014-03-26 山东齐都药业有限公司 用于制备2-丙基庚酸的新中间体、其制备方法及2-丙基庚酸的制备方法

Also Published As

Publication number Publication date
JPWO2006075596A1 (ja) 2008-06-12

Similar Documents

Publication Publication Date Title
US20100267988A1 (en) Processes for preparing intermediate compounds useful for the preparation of cinacalcet
WO2006075596A1 (fr) Procede servant a produire un compose acide 2-allylcarboxylique
JP5211876B2 (ja) 高純度２’−トリフルオロメチルプロピオフェノンの製造方法
JP2011121951A (ja) テトラヒドロピラン−４−オン及びピラン−４−オンの製法
US20190194099A1 (en) Method for producing 3,7-dimethyl-7-octenol and method for producing 3,7-dimethyl-7-octenyl carboxylate compound
US8609886B2 (en) Method for producing high purity terminal olefin compound
EP1720851B1 (fr) Procede de synthese d'heliotropine et de ses derives
JP3795970B2 (ja) α，β−不飽和アルデヒドの製造方法
JP3229408B2 (ja) 新規な４−アミノ−５−ヘキセン酸の製法
CN1334803A (zh) 制备(2s,4r,9s)－八氢－1h－吲哚－2－甲酸的方法及其中间体
JP5115762B2 (ja) ４−ホルミルピペリジンアセタール誘導体の製造方法
JP4800933B2 (ja) シクロプロパンモノアセタール誘導体の製造方法およびその中間体
JP2009155232A (ja) ２−（１−ヒドロキシアルキル）シクロアルカノンとその脱水体との混合物の製造方法
JP3357147B2 (ja) ５−フェニルペンタン酸の製造方法
JP5187534B2 (ja) Ｎ−ｔｅｒｔ−ブトキシカルボニル−４−ホルミルピペリジンの製造方法
JP2000063373A (ja) ４−ヒドロキシメチル−γ−ブチロラクトンの製造方法および該製造方法に有用な中間体並びに該中間体の製造方法
CN115197040A (zh) (6z,9z)-6,9-十二碳二烯-1-炔及其制备方法
JP2003113189A (ja) シクロペンタベンゾフラン誘導体の製造方法及びその製造原料となる新規化合物
JPH0819045B2 (ja) ３―ホルミル―クロトン酸―アルキルエステルの製法
JP2002308815A (ja) ラバンジュラールの製造方法
JPH11189566A (ja) フルオロアルキルカルボン酸の製造方法
JPH08333295A (ja) ６−メチルヘプタン−２−オンの製造方法
JPH093025A (ja) １，６−ジオキシイミノヘキサンの製造方法
JP2002138087A (ja) セサモールギ酸エステル及びセサモールの製造方法
JP2008150301A (ja) ４−ヒドロキシメチルテトラヒドロピラン化合物の製法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2006552923

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06711532

Country of ref document: EP

Kind code of ref document: A1

WWW Wipo information: withdrawn in national office

Ref document number: 6711532

Country of ref document: EP