WO2022014413A1 - Procédé de production de 1,1,3-triméthyl-4-aminoindane optiquement actif - Google Patents

Procédé de production de 1,1,3-triméthyl-4-aminoindane optiquement actif Download PDF

Info

Publication number
WO2022014413A1
WO2022014413A1 PCT/JP2021/025488 JP2021025488W WO2022014413A1 WO 2022014413 A1 WO2022014413 A1 WO 2022014413A1 JP 2021025488 W JP2021025488 W JP 2021025488W WO 2022014413 A1 WO2022014413 A1 WO 2022014413A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
trimethyl
optically active
aminoindane
group
Prior art date
Application number
PCT/JP2021/025488
Other languages
English (en)
Japanese (ja)
Inventor
弘寿 萩谷
Original Assignee
住友化学株式会社
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 住友化学株式会社 filed Critical 住友化学株式会社
Publication of WO2022014413A1 publication Critical patent/WO2022014413A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B57/00—Separation of optically-active compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/82—Purification; Separation; Stabilisation; Use of additives
    • C07C209/86—Separation
    • C07C209/88—Separation of optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C211/57—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems of the carbon skeleton
    • C07C211/60—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems of the carbon skeleton containing a ring other than a six-membered aromatic ring forming part of at least one of the condensed ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

Definitions

  • the present invention relates to a method for producing optically active 1,1,3-trimethyl-4-aminoindane.
  • Patent Document 1 describes that optically active 1,1,3-trimethyl-4-aminoindane is useful as a synthetic intermediate for a compound having a plant disease preventive effect. Further, in Patent Document 1, D-tartaric acid is used to optically resolve the racemic 1,1,3-trimethyl-4-aminoindane to obtain (R) -1,1,3-trimethyl-4-. It is also stated that aminoindane can be obtained.
  • An object of the present invention is to provide a new method for producing optically active 1,1,3-trimethyl-4-aminoindane by a preferential crystallization method with an achiral acid without using an optically active acid. Is.
  • the present invention includes the following inventions.
  • the optically active 1,1,3-trimethyl-4-aminoindan comprises a second step of mixing the acid salt and the base to obtain an optically active 1,1,3-trimethyl-4-aminoindan. Manufacturing method.
  • the optically active 1,1,3-trimethyl-4-aminoindane obtained in the second step is more than the optical purity of the optically active 1,1,3-trimethyl-4-aminoindane used in the first step.
  • the production method according to [1] which is characterized by high optical purity.
  • the optical purity of the optically active 1,1,3-trimethyl-4-aminoindane used in the first step is 40% e. e.
  • the optical purity of the optically active 1,1,3-trimethyl-4-aminoindane obtained in the second step is 89% e. e.
  • Acids are sulfuric acid, sodium hydrogensulfate, potassium hydrogensulfate, sulfamic acid, methanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, phenylphosphate, diphosphate.
  • One or more acids selected from the group consisting of hydrogenphenyl, nitrate, tetrafluoroboric acid, oxalic acid, trifluoroacetic acid, trichloroacetic acid, 2-nitrobenzoic acid, chloroacetic acid, and bromoacetic acid, [1]-[ 4] The manufacturing method according to any one of the above items.
  • the optical purity of 1,1,3-trimethyl-4-aminoindane can be efficiently improved.
  • the present invention is a method for producing optically active 1,1,3-trimethyl-4-aminoindan, wherein the production method is described in the following steps, that is, optically active 1,1,3 in the presence of a solvent.
  • -Mixing trimethyl-4-aminoindane and an achiral acid to precipitate their acid salts (first step), and mixing the acid salts obtained in the first step with a base to obtain optical light.
  • the step (second step) for obtaining an active 1,1,3-trimethyl-4-aminoindan is included.
  • optically active 1,1,3-trimethyl-4-aminoindane the racemic mixture of the R-form, which will be described later, is contained in enantiorich. It means the form of the body or its R body itself.
  • the optically active 1,1,3-trimethyl-4-aminoindane used in the first step has an optical purity of 40% e. e.
  • the optical purity of the optically active 1,1,3-trimethyl-4-aminoindane obtained in the second step tends to be high (usually 89% e.e.). e. Or more, for example, 91% e.e.
  • the optically active 1,1,3-trimethyl-4-aminoindane preferably contains a large amount of R-form in that it is useful as a synthetic intermediate of the compound having a plant disease preventive effect described in Patent Document 1.
  • the optically active 1,1,3-trimethyl-4-aminoindane used in the first step contains a large amount of R-form, usually, the optically active 1,1,3-trimethyl-4-amino obtained in the second step is obtained.
  • Indan contains a lot of R-forms. The structural formulas of the R-form and the S-form of 1,1,3-trimethyl-4-aminoindane are shown below.
  • 2,2,4-trimethyl-1-quinoline is acylated with an optically active acylating agent and then hydrogenated to be optically active.
  • optically active acylating agent examples thereof include a production method in which a 2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline derivative is obtained, further isomerized with sulfuric acid, and then hydrolyzed (for example, JP-A-7-215921). See publication). Further, by asymmetric hydrogenating the 2,2,4-trimethyl-1-quinoline derivative, the above-mentioned optically active 2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline derivative can be obtained.
  • optically active 1,1,3-trimethyl-4-aminoindane obtained by these methods can be provided.
  • the acid may be an achiral acid, and among the optically active 1,1,3-trimethyl-4-aminoindane, a large amount of the optically active salt of the optically active substance can be preferentially precipitated. It may be an acid.
  • an acid having an acid dissociation constant (pKa) of less than 2.8 is usually used.
  • the acid dissociation constant is determined by the equilibrium constant (Ka) of the ionization equilibrium of the acid when the acid dissociation reaction in which hydrogen ions are released from the acid, or the dissociation constant (pKa) which is a negative common logarithm thereof. It is an index showing the strength of acid expressed.
  • Acids with an acid dissociation constant (pKa) of less than 2.8 include sulfuric acid, hydrogen sulfate, sulfamic acid, organic sulfonic acid, hydrohalogenate, phosphoric acid, organic phosphoric acids, nitrate, tetrafluoroboric acid and carboxylic acid. Acids are mentioned, and it is preferable to use one or more acids selected from the group consisting of these acids.
  • the hydrogen sulfate include hydrogen sulfate alkali metal salts such as sodium hydrogen sulfate, lithium hydrogen sulfate, and potassium hydrogen sulfate.
  • Examples of the organic sulfonic acid include methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, taurine and the like.
  • Examples of the hydrogen halide include hydrochloric acid, hydrobromic acid, and hydrogen iodide.
  • Examples of organic phosphoric acids include phenyl dihydrogen phosphate, ethyl dihydrogen phosphate, phenylphosphonic acid, and methylphosphonic acid.
  • carboxylic acid examples include oxalic acid, trichloroacetic acid, trifluoroacetic acid, dichloroacetic acid, monochloroacetic acid, monobromoacetic acid, 2-nitrobenzoic acid, pentafluorophenylcarboxylic acid and the like.
  • one or more acids selected from the group consisting of sulfuric acid, hydrogen sulfate, sulfamic acid, organic sulfonic acid, hydrohalic acid, phosphoric acid, organic phosphoric acids, nitric acid, tetrafluoroboric acid, and carboxylic acid. It is more preferable to use it.
  • Sulfuric acid sodium hydrogensulfate, potassium hydrogensulfate, sulfamic acid, methanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, phenylphosphate, dihydrogenphobic phenyl, nitrate, tetra It is further preferred to use one or more acids selected from the group consisting of fluoroboric acid, oxalic acid, trifluoroacetic acid, trichloroacetic acid, 2-nitrobenzoic acid, chloroacetic acid, and bromoacetic acid.
  • the amount of the acid used is usually 0.7 mol to 1.5 mol, preferably 0 in the case of an acid other than sulfuric acid, with respect to 1 mol of optically active 1,1,3-trimethyl-4-aminoindan.
  • the range is from 7.7 mol to 1.0 mol, and in the case of sulfuric acid, it is usually in the range of 0.35 mol to 0.5 mol, preferably 0.35 mol to 0.45 mol.
  • the solvent examples include alcohol solvents such as methanol, ethanol, and 2-propanol; water; ether solvents such as tetrahydrofuran; nitrile solvents such as acetonitrile; ester solvents such as ethyl acetate; aromatic hydrocarbons such as toluene, xylene, and ethylbenzene. Solvents; halogenated aromatic hydrocarbon solvents such as monochlorobenzene; aliphatic hydrocarbon solvents such as heptane and hexane; and alicyclic hydrocarbon solvents such as cyclopentane and cyclohexane, alcohol solvents and aromatics.
  • a hydrocarbon solvent and water are preferable.
  • the amount of the solvent used is usually 0.5 parts by weight to 20 parts by weight, preferably 1.0 part by weight to 10 parts by weight, based on 1 part by weight of 1,1,3-trimethyl-4-aminoindane. It is a range.
  • the mixing temperature is usually in the range of 20 ° C to 100 ° C.
  • the mixing order may be that 1,1,3-trimethyl-4-aminoindane, an acid and a solvent may be mixed at one time, or after mixing the acid and the solvent, the resulting mixture may be mixed with 1,1,1. 3-trimethyl-4-aminoindane may be added. A mixture of an acid and a solvent may be added to 1,1,3-trimethyl-4-aminoindane. Further, after mixing 1,1,3-trimethyl-4-aminoindane with a solvent, an acid or a mixture of an acid and a solvent may be added to the obtained mixture.
  • a method of mixing 1,1,3-trimethyl-4-aminoindane with a solvent and then adding an acid or a mixture of the acid and the solvent to the obtained mixture is preferable. If the crystals do not precipitate even after mixing and cooling, the crystals may be precipitated by partially distilling off the solvent.
  • Mixing may be performed collectively, continuously, or divided (for example, dropped).
  • an acid is added to a mixture of 1,1,3-trimethyl-4-aminoindane and a solvent, the acid may be added all at once or continuously, but may be added in portions. Is preferable.
  • a salt of optically active 1,1,3-trimethyl-4-aminoindane may be precipitated only by mixing an acid with a solution of optically active 1,1,3-trimethyl-4-aminoindane. Usually, by cooling the resulting mixture, the optically active acid salt of 1,1,3-trimethyl-4-aminoindane can be precipitated. By separating the acid salt precipitated from the mixture by a solid-liquid separation treatment such as filtration, the optically active acid salt of 1,1,3-trimethyl-4-aminoindan and the remaining 1,1,3- It can be separated into a solution containing trimethyl-4-aminoindan and its acid salt. If the optically active acid salt of 1,1,3-trimethyl-4-aminoindane does not precipitate even after cooling, the acid salt may be precipitated by distilling off a part of the solvent.
  • the temperature after cooling is lower than the above-mentioned mixing temperature, preferably in the range of ⁇ 20 ° C. to 30 ° C., and more preferably in the range of ⁇ 10 ° C. to 20 ° C.
  • the cooling rate is not particularly limited, but is usually in the range of about 1 ° C./hour to 100 ° C./hour.
  • optically active acid salt of 1,1,3-trimethyl-4-aminoindane extracted in the first step may be used as it is in the next second step, but at least one selected from the above solvents. It may be served after washing with the solvent of. Further, it may be dried and then subjected to the second step if necessary.
  • any base having a base strength capable of decomposing the optically active acid salt of 1,1,3-trimethyl-4-aminoindane can be used without particular limitation.
  • the base include an inorganic base and an organic base.
  • the inorganic base include alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metals carbonate, and alkali metals phosphate.
  • the alkali metal hydroxide include sodium hydroxide and potassium hydroxide.
  • Examples of the alkaline earth metal hydroxide include calcium hydroxide and magnesium hydroxide.
  • Examples of the alkali metal carbonate include potassium carbonate and sodium carbonate.
  • Alkaline carbonate earth metals include calcium carbonate and magnesium carbonate.
  • alkali metal phosphate examples include trisodium phosphate and tripotassium phosphate.
  • Alkali metal hydroxides are preferred.
  • organic bases include tertiary amines, secondary amines, and primary amines.
  • tertiary amine examples include triethylamine, tripropylamine, tributylamine and the like.
  • secondary amine examples include diethylamine, dipropylamine, dibutylamine and the like.
  • Examples of the primary amine include butylamine and benzylamine. It is preferably a tertiary amine.
  • the amount of the base is usually in the range of 0.5 mol to 3 mol in terms of base with respect to 1 mol of the acid used in the first step.
  • the mixing temperature is usually in the range of 10 ° C to 80 ° C.
  • the mixing of the acid salt and the base obtained in the first step may be carried out in the presence of an organic solvent and / or water.
  • organic solvent include aromatic hydrocarbon solvents such as toluene, xylene and ethylbenzene; halogenated aromatic hydrocarbon solvents such as monochlorobenzene; aliphatic hydrocarbon solvents such as heptane and hexane; alicyclic type such as cyclopentane and cyclohexane.
  • examples include, but are not limited to, hydrocarbon solvents; ether solvents such as diethyl ether and tert-butyl methyl ether; and ester solvents such as ethyl acetate; and mixed solvents thereof.
  • the total amount of the organic solvent and / or water used is usually 10 parts by weight or less with respect to 1 part by weight of the acid salt.
  • the mixing order may be such that the optically active acid salt of 1,1,3-trimethyl-4-aminoindan, the base in an aqueous solution if necessary, and the organic solvent if necessary may be mixed at once.
  • the acid salt and, if necessary, a mixture with an organic solvent, and if necessary, an aqueous solution of the base may be mixed.
  • the acid salt may be added to a mixture of an aqueous solution of a base and an organic solvent, if necessary.
  • the mixture After completion of mixing, the mixture is usually separated into an organic layer and an aqueous layer, which are separated to obtain an organic layer, and if necessary, an organic solvent is distilled off to obtain an optically active 1, 1,3-trimethyl-4-aminoindane can be taken out.
  • the optical purity of the optically active 1,1,3-trimethyl-4-aminoindane thus obtained is usually the optically active 1,1,3-trimethyl-4-aminoindane used in the first step. Higher than the optical purity of.
  • the optically active 1,1,3-trimethyl-4-aminoindan is used for the amidation reaction D described later, the acid salt is subjected to the reaction with the compound represented by the formula (1-3) as it is.
  • the acid salt is neutralized by the base in the reaction system to give optically active 1,1,3-trimethyl-4-aminoindan, which reacts with the compound represented by the formula (1-3). Therefore, the second step of the present invention and the amidation reaction D can be continuously performed.
  • the optically active 1,1,3-trimethyl-4-aminoindane obtained in the second step and the formula (1) (In the formula, R 1 and R 2 each independently represent a C1-C6 alkyl group or a hydrogen atom which may be substituted with one or more halogen atoms, and R 3 is a halogen atom or a hydroxy group. , Or a C1-C6 alkoxy group that may be substituted with one or more halogen atoms.)
  • the formula (2) (In the formula, R 1 and R 2 have the same meanings as above.
  • the carbon atom marked with * represents an asymmetric carbon atom.)
  • the process of obtaining the compound represented by the above will be described.
  • the reaction between the optically active 1,1,3-trimethyl-4-aminoindane obtained in the second step and the compound represented by the formula (1) is referred to as "amidation reaction" in the present specification. May be described.
  • CX-CY in the present specification means that the number of carbon atoms is X to Y. That is, the notation “C1-C6” means that the number of carbon atoms is 1 to 6.
  • Examples of the C1-C6 alkyl group represented by R 1 and R 2 in the formulas (1) and (2) and which may be substituted with one or more halogen atoms include a methyl group, an ethyl group and an n-propyl group.
  • Group isopropyl group, n-butyl group, sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group, trifluoromethyl group, difluoromethyl group, monofluoromethyl group, perfluoroethyl group, perfluoro n -Propyl group, perfluoroisopropyl group, perfluoron-butyl group, perfluorosec-butyl group, perfluorotert-butyl group, perfluoron-pentyl group, perfluoron-hexyl group, trichloromethyl group, tribromomethyl group, and triiode Examples include a methyl group.
  • R 1 a hydrogen atom or a methyl group is preferable, and a hydrogen atom is more preferable.
  • Examples of the C1-C6 alkoxy group represented by R 3 which may be substituted with one or more halogen atoms include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group and sec-.
  • a chlorine atom, an ethoxy group or a hydroxyl group are preferred, and a chlorine atom is more preferable.
  • Examples of the compound represented by the formula (1) include 1-methyl-3-difluoromethylpyrazole-4-carboxylate ethyl, 1. -Methyl-3-difluoromethylpyrazole-4-carboxylic acid, 1-methyl-3-difluoromethylpyrazole-4-carboxylic acid chloride and the like can be mentioned.
  • optically active compound (2) examples include (R)-(-)-N- (1). , 1,3-trimethylindan-4-yl) -1-methyl-3-difluoromethylpyrazole-4-carboxylic acid amide and the like.
  • the amidation reaction may be carried out under the condition that the optically active 1,1,3-trimethyl-4-aminoindane obtained in the second step reacts with the compound (1). , B, C or D is preferred.
  • Amidation reaction A is an optically active 1,1,3-trimethyl-4-aminoindan obtained in the second step
  • R 3 is a hydroxy group in the formula (1) (herein, Hereinafter, it may be referred to as “compound (1-1)”) in the presence of a dehydration condensing agent to obtain an optically active compound (2).
  • compound (1-1) a hydroxy group in the formula (1)
  • R 1 and R 2 have the same meanings as described above.
  • dehydration condensing agent examples include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, carbodiimide compounds such as 1,3-dicyclohexylcarbodiimide, and (benzotriazole-1-yloxy) tris (dimethylamino). Phosphonium hexafluorophosphate may be mentioned.
  • the amount of the dehydration condensing agent used is usually in the range of 1 mol to 5 mol per 1 mol of the compound (1-1).
  • the amount of optically active 1,1,3-trimethyl-4-aminoindane used is usually in the range of 0.5 mol to 3 mol per 1 mol of compound (1-1).
  • the reaction between the optically active 1,1,3-trimethyl-4-aminoindane and compound (1-1) is usually carried out in the presence of a solvent inert to the reaction.
  • solvents include ether solvents such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, and tert-butyl methyl ether; aliphatic hydrocarbon solvents such as hexane, heptane, and octane; aromatic carbides such as toluene, xylene, and ethylbenzene.
  • Hydrogen solvent Halogened hydrocarbon solvent such as chlorobenzene; Ester solvent such as butyl acetate and ethyl acetate; Nitrile solvent such as acetonitrile; Acid amide solvent such as N, N-dimethylformamide; Sulfoxide solvent such as dimethyl sulfoxide, and Examples thereof include a nitrogen-containing aromatic compound solvent such as pyridine, and a mixed solution of two or more of these.
  • the amount of the solvent used is usually in the range of 1 part by weight to 20 parts by weight with respect to 1 part by weight of the compound (1-1).
  • the reaction temperature is usually in the range of ⁇ 20 ° C. to 150 ° C., and the reaction time is usually in the range of 1 hour to 24 hours.
  • the optically active compound (2) can be taken out by mixing it with an aqueous solution of an acid such as acetic acid to precipitate a solid, and filtering the obtained mixture.
  • a base such as an aqueous solution of sodium hydrogen carbonate, an aqueous solution of sodium carbonate, an aqueous solution of ammonium chloride, an aqueous solution of sodium hydroxide or an aqueous solution of potassium hydroxide; or an aqueous solution of hydrochloric acid, sulfuric acid, phosphoric acid or
  • the optically active compound (2) can be taken out by mixing it with an aqueous solution of an acid such as acetic acid to precipitate a solid, and filtering the obtained mixture.
  • the optically active compound (2) can be taken out by extracting the obtained mixture with an organic solvent and performing post-treatment operations such as separating, drying and concentrating the organic layer.
  • the organic layer is water: aqueous solution of alkali metal hydrogen carbonate such as sodium hydrogen carbonate aqueous solution: aqueous solution of alkali metal carbonate such as sodium carbonate aqueous solution: ammonium chloride aqueous solution: alkali metal water such as sodium hydroxide aqueous solution and potassium hydroxide aqueous solution.
  • Aqueous solution of oxide Alternatively, it may be washed with an aqueous solution of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid and acetic acid. Cleaning of the organic layer is usually carried out in the range of 0 ° C to 70 ° C, preferably 20 ° C to 60 ° C.
  • the extracted optically active compound (7) can be further purified by column chromatography, recrystallization and the like.
  • metal chlorides such as titanium tetrachloride, zirconium tetrachloride, and aluminum chloride: titanium ethoxydo, titanium propoxide, zirconium ethoxydo, zirconium propoxide, aluminum ethoxydo, aluminum propoxide, antimonate,
  • metal alkoxide compounds such as antimonpropoxide: tetrakis (dimethylamino) titanium, dichlorobis (dimethylamino) titanium, and metal amide compounds such as tetrakis (diethylamino) titanium: boric acid, 3,5-bis (trifluoromethyl) phenyl.
  • Boron compounds such as boronic acid, 2,4-bis (trifluoromethyl) phenylboronic acid, and pentafluorophenylboronic acid: triphenylmethyltetrakis (pentafluorophenyl) borate, triphenylmethyltetrakis (3,5-bistrifluoro) Examples thereof include borate compounds such as methylphenyl) borate and N, N-dimethylanilinium tetrakis (pentafluorophenyl) borate.
  • the amount of Lewis acid used is usually in the range of 0.001 mol to 3 mol per 1 mol of compound (1-1).
  • the amount of optically active 1,1,3-trimethyl-4-aminoindane used is usually in the range of 0.5 mol to 3 mol per 1 mol of compound (1-1).
  • the reaction of the optically active 1,1,3-trimethyl-4-aminoindane with compound (1-1) is usually carried out in the presence of a solvent inert to the reaction.
  • a solvent inert examples include the above-mentioned solvents as the solvents that can be used for the amidation reaction A.
  • the amount of the solvent used is usually in the range of 1 part by weight to 20 parts by weight with respect to 1 part by weight of the compound (1-1).
  • the reaction temperature is usually in the range of ⁇ 20 ° C. to 150 ° C.
  • the reaction time is usually in the range of 1 hour to 120 hours, and it is preferable to carry out the reaction while removing the by-product water.
  • the optically active compound (2) can be taken out by performing the same treatment as in the amidation reaction A.
  • Amidation reaction C is an optically active 1,1,3-trimethyl-4-aminoindan obtained in the second step, R 3 in the formula (1) is optionally substituted with one or more halogen atoms
  • a compound which is also a good C1-C10 alkoxy group hereinafter, may be referred to as “compound (1-2)” in the present specification
  • compound (1-2) is reacted in the presence of a Lewis acid or a Lewis base for optical activity.
  • This is a step of obtaining compound (2).
  • R 1 and R 2 are as defined above, and R 3 'represents one or more halogen atoms which may be substituted C1-C6 alkoxy group.
  • Lewis acids include metal chlorides such as titanium tetrachloride, zirconium tetrachloride, and aluminum chloride, and titanium ethoxydo, titanium propoxide, zirconium ethoxydo, zirconium propoxide, aluminum ethoxydo, aluminum propoxide, and antimonate. , And metal alkoxide compounds such as antimonopropoxide.
  • the amount of Lewis acid used is usually in the range of 0.01 mol to 3 mol per 1 mol of compound (1-2).
  • the amount of optically active 1,1,3-trimethyl-4-aminoindane used is usually in the range of 0.5 mol to 3 mol per 1 mol of compound (1-2).
  • Lewis bases include metal alkoxide compounds such as sodium methoxyd, sodium ethoxydo, sodium tert-butoxide, potassium methoxyd, potassium ethoxydo and potassium tert-butoxide: metal hydrides such as sodium hydride: lithium diisopropylamide and tert.
  • -Lithium compounds such as butyl lithium: silicon compounds such as sodium hexamethyldisilazane and potassium hexamethyldisilazane: aluminum compounds such as trimethylaluminum, triethylaluminum and triisobutylaluminum.
  • the amount of Lewis base used is usually in the range of 0.01 mol to 3 mol per 1 mol of compound (1-2).
  • the amount of optically active 1,1,3-trimethyl-4-aminoindane used is usually in the range of 0.5 mol to 3 mol per 1 mol of compound (1-2).
  • the reaction of the optically active 1,1,3-trimethyl-4-aminoindane with compound (1-2) is usually carried out in the presence of a solvent inert to the reaction.
  • a solvent inert examples include the above-mentioned solvents as the solvents that can be used for the amidation reaction A.
  • the amount of the solvent used is usually in the range of 1 part by weight to 20 parts by weight with respect to 1 part by weight of the compound (1-2).
  • the reaction temperature is usually in the range of ⁇ 20 ° C. to 150 ° C., and the reaction time is usually in the range of 1 hour to 110 hours, and it is preferable to carry out the reaction while removing the by-product alcohol.
  • the optically active compound (2) can be taken out by performing the same treatment as in the amidation reaction A.
  • Amidation reaction D is an optically active 1,1,3-trimethyl-4-aminoindan obtained in the second step, and R 3 is a halogen atom in the above formula (1) (herein, Hereinafter, it may be referred to as “compound (1-3)”) in the presence of a base to obtain an optically active compound (2).
  • compound (1-3) a halogen atom in the above formula (1)
  • the base examples include alkali metal carbonates such as sodium carbonate and potassium carbonate; tertiary amines such as triethylamine and diisopropylethylamine; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
  • the amount of the base used is usually in the range of 5 mol, preferably 1 mol to 3 mol, from the catalytic amount, relative to 1 mol of the optically active 1,1,3-trimethyl-4-aminoindane. As described above, when the optically active 1,1,3-trimethyl-4-aminoindane is used as it is in the amidation reaction D without decomposing the acid salt obtained in the first step, it is necessary for its neutralization.
  • the amount of the base to be used may be determined in consideration of the amount of the base.
  • the amount of the compound (1-3) to be used is usually 0.5 mol to 1.5 mol, preferably 0.8 mol, based on 1 mol of the optically active 1,1,3-trimethyl-4-aminoindan. From 1.3 mol, more preferably in the range of 1.0 mol to 1.2 mol.
  • the reaction between the optically active 1,1,3-trimethyl-4-aminoindane and compound (1-3) is usually carried out in the presence of a solvent.
  • the solvent may be any one inert to the reaction, for example, an aliphatic hydrocarbon solvent such as pentane, hexane, heptane, octane and cyclohexane; an aromatic hydrocarbon solvent such as toluene, xylene and ethylbenzene; dichloromethane, chloroform.
  • 1,2-Dichloroethane and halogenated aliphatic hydrocarbon solvents such as carbon tetrachloride; halogenated aromatic hydrocarbon solvents such as chlorobenzene, dichlorobenzene and trichlorobenzene; diethyl ether, diisopropyl ether, tert-butylmethyl ether, cyclohexyl Ether solvents such as methyl ether, ethylene glycol dimethyl ether, tetrahydrofuran and dioxane; ester solvents such as ethyl acetate and butyl acetate; nitrile solvents such as acetonitrile; and mixed solutions of two or more of these include aromatic hydrocarbon solvents.
  • aromatic hydrocarbon solvents such as carbon tetrachloride
  • halogenated aromatic hydrocarbon solvents such as chlorobenzene, dichlorobenzene and trichlorobenzene
  • Halogenized aromatic hydrocarbon solvents and ether solvents are preferred, with toluene, xylene, ethylbenzene, chlorobenzene and tetrahydrofuran more preferred.
  • the amount of the solvent used is preferably 1 part by weight to 20 parts by weight, more preferably 2 parts by weight to 10 parts by weight, based on 1 part by weight of the optically active 1,1,3-trimethyl-4-aminoindane. It is a range.
  • the reaction temperature is usually in the range of ⁇ 20 ° C. to 80 ° C., preferably 0 ° C. to 70 ° C., more preferably 20 ° C. to 60 ° C., and the reaction time is usually in the range of 0.1 hour to 24 hours.
  • the optically active compound (2) can be taken out by performing the same treatment as in the amidation reaction A.
  • the extracted optically active compound (2) can be further purified by column chromatography, recrystallization and the like, and is preferably purified.
  • a purification method a method in which the optically active compound (2) is dissolved in a solvent to prepare a solution and recrystallization is performed using the solution is preferable. Seed crystals may be used for recrystallization.
  • Such solvents include aliphatic hydrocarbon solvents such as pentane, hexane, heptane, octane and cyclohexane; aromatic hydrocarbon solvents such as toluene, xylene and ethylbenzene; dichloromethane, chloroform, 1,2-dichloroethane and carbon tetrachloride and the like.
  • Halogenated aliphatic hydrocarbon solvent Halogenized aromatic hydrocarbon solvent such as chlorobenzene, dichlorobenzene and trichlorobenzene; diethyl ether, diisopropyl ether, tert-butylmethyl ether, cyclohexylmethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran and dioxane and the like.
  • Ether solvents include aliphatic hydrocarbon solvents, Aromatic hydrocarbon solvents, halogenated aromatic hydrocarbon solvents and ester solvents are preferred, with toluene, xylene, ethylbenzene, hexane, heptane and ethyl acetate more preferred.
  • Example 12 ⁇ Amidation reaction D> 14.0 parts of 1-methyl-3-difluoromethylpyrazole-4-carboxylic acid and 35.1 parts of xylene were mixed under a nitrogen atmosphere at room temperature. The resulting mixture was heated to 100 ° C. 11.2 parts of thionyl chloride was added dropwise to the obtained mixture over 5 hours. The resulting mixture was stirred at 100 ° C. for 15 hours and then cooled to 40 ° C. Thionyl chloride and xylene were distilled off from the obtained reaction mixture under reduced pressure to obtain brown 1-methyl-3-difluoromethylpyrazole-4-carboxylic acid chloride.
  • optically active (R) -1,1,3-trimethyl-4-aminoindane can be efficiently produced.
  • Such a compound prepares (R)-(-)-(1,1,3-trimethylindan-4-yl) -1-methyl-3-difluoromethylpyrazole-4-carboxylic acid amide having a plant disease preventive effect. Useful as an intermediate.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'objectif de la présente invention est de fournir un nouveau procédé de production de 1,1,3-triméthyl-4-aminoindane optiquement actif par un procédé de cristallisation préférentielle utilisant un acide achiral, mais aucun acide optiquement actif.　La présente invention concerne un procédé de production de 1,1,3-triméthyl-4-aminoindane optiquement actif, le procédé comprenant : une première étape consistant à mélanger le 1,1,3-triméthyl-4-aminoindane optiquement actif et un acide achiral en présence d'un solvant de manière à entraîner la précipitation d'un sel d'acide de ceux-ci ; et une seconde étape consistant à mélanger le sel d'acide obtenu à la première étape avec une base de façon à obtenir du 1,1,3-triméthyl-4-aminoindane optiquement actif.
PCT/JP2021/025488 2020-07-17 2021-07-06 Procédé de production de 1,1,3-triméthyl-4-aminoindane optiquement actif WO2022014413A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2020122761A JP2023120459A (ja) 2020-07-17 2020-07-17 光学活性な１，１，３－トリメチル－４－アミノインダンの製造方法
JP2020-122761 2020-07-17

Publications (1)

Publication Number Publication Date
WO2022014413A1 true WO2022014413A1 (fr) 2022-01-20

Family

ID=79555374

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2021/025488 WO2022014413A1 (fr) 2020-07-17 2021-07-06 Procédé de production de 1,1,3-triméthyl-4-aminoindane optiquement actif

Country Status (2)

Country Link
JP (1) JP2023120459A (fr)
WO (1) WO2022014413A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6210066A (ja) * 1985-07-08 1987-01-19 Sumitomo Chem Co Ltd ピラゾ−ルカルボキサミド誘導体およびそれを有効成分とする殺菌剤
JPH04108774A (ja) * 1990-08-25 1992-04-09 Mitsubishi Kasei Corp 光学活性なｎ―インダニルニコチン酸アミド誘導体及びこれを有効成分とする農園芸用殺菌剤
JP2010513316A (ja) * 2006-12-14 2010-04-30 ノップ ニューロサイエンシーズ、インク． （ｒ）−プラミペキソール組成物およびその使用法
WO2015118793A1 (fr) * 2014-02-07 2015-08-13 住友化学株式会社 Procédé de production de (r)-1,1,3-triméthyl-4-aminoindane

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6210066A (ja) * 1985-07-08 1987-01-19 Sumitomo Chem Co Ltd ピラゾ−ルカルボキサミド誘導体およびそれを有効成分とする殺菌剤
JPH04108774A (ja) * 1990-08-25 1992-04-09 Mitsubishi Kasei Corp 光学活性なｎ―インダニルニコチン酸アミド誘導体及びこれを有効成分とする農園芸用殺菌剤
JP2010513316A (ja) * 2006-12-14 2010-04-30 ノップ ニューロサイエンシーズ、インク． （ｒ）−プラミペキソール組成物およびその使用法
WO2015118793A1 (fr) * 2014-02-07 2015-08-13 住友化学株式会社 Procédé de production de (r)-1,1,3-triméthyl-4-aminoindane

Also Published As

Publication number Publication date
JP2023120459A (ja) 2023-08-30

Similar Documents

Publication Publication Date Title
AU2014381760B2 (en) Method for producing (R)-1,1,3-trimethyl-4-aminoindane
CA2570833C (fr) Synthese de chlorhydrate de (z)-1-phenyl-1-diethylaminocarbonyl-2- aminoethylcyclopropane
JP5425806B2 (ja) プロパルギル化アミノインダン誘導体の合成方法
JP2001192345A (ja) パーフルオロアルカジエンの製造方法
WO2014037886A1 (fr) Procédé de préparation de chlorhydrate de lurasidone
WO2022014413A1 (fr) Procédé de production de 1,1,3-triméthyl-4-aminoindane optiquement actif
US20150203438A1 (en) Method for producing (r)-1, 1, 3-trimethyl-4-aminoindane
CN115836041B (zh) 光学活性的化合物的制造方法
TW201302672A (zh) 不飽和羧酸醯胺組成物之製造方法
JP4667593B2 (ja) ２−アルキル−２−アダマンチル（メタ）アクリレート類の製造法
CN111689993A (zh) 一种新的含硼类佐米药物关键中间体手性α-氨基硼酸酯的制备方法
JP4258658B2 (ja) アセチレン化合物の製造方法
JP4389548B2 (ja) フルオレン骨格を有するアリールアミン誘導体と芳香族炭化水素との包接化合物、及びアリールアミン誘導体の分離精製方法。
JP4218310B2 (ja) 光学活性２−アミノ−２−フェニルエタノール類の製造方法およびその中間体
JP4265259B2 (ja) クロロ蟻酸ベンジルエステル類の製造方法
JP2003238500A (ja) 含フッ素３級アミン化合物及び含フッ素４級アンモニウム塩の製造方法
JP2001302647A (ja) ２−置換−１，２−ベンズイソチアゾール−３−オン類の精製方法
JP2003517029A (ja) トリフルオロメチルアセトフェノンの製造方法
JP2003095991A (ja) 光学活性３，３，３−トリフルオロ−２−ヒドロキシ−２−メチルプロピオン酸の製造法
JPWO2006059774A1 (ja) ジアリルビスフェノール化合物の精製方法
JP2004083457A (ja) 光学活性２−アミノ−２−フェニルエタノール類の製造法およびその中間体
JP2013124236A (ja) ハロゲン化アルキルアミンのハロゲン化水素酸塩の製造方法
JP2004250340A (ja) ４−ヒドラジノテトラヒドロピラン化合物又はその酸塩の製法
JPH01203338A (ja) シクロヘキサンの分離方法
ITMI20011162A1 (it) Alogenoarilsolfonammidi aventi caratteristiche antitumorali

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21842365

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21842365

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP