WO2013080583A1 - Procédé de production d'un sel de triolborate organique - Google Patents

Procédé de production d'un sel de triolborate organique Download PDF

Info

Publication number
WO2013080583A1
WO2013080583A1 PCT/JP2012/062906 JP2012062906W WO2013080583A1 WO 2013080583 A1 WO2013080583 A1 WO 2013080583A1 JP 2012062906 W JP2012062906 W JP 2012062906W WO 2013080583 A1 WO2013080583 A1 WO 2013080583A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
carbon atoms
general formula
phenyl
borate salt
Prior art date
Application number
PCT/JP2012/062906
Other languages
English (en)
Japanese (ja)
Inventor
靖典 山本
Original Assignee
和光純薬工業株式会社
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 和光純薬工業株式会社 filed Critical 和光純薬工業株式会社
Priority to JP2013547009A priority Critical patent/JP5928479B2/ja
Publication of WO2013080583A1 publication Critical patent/WO2013080583A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/04—Esters of boric acids

Definitions

  • the present invention relates to a method for producing a novel organic triol borate salt.
  • Organic triol borate salts are used for organic synthetic chemistry reactions such as carbon-carbon bond formation reaction, carbon-nitrogen bond formation reaction, carbon-oxygen bond formation reaction, carbon-sulfur bond formation reaction, especially for cross-coupling reaction and addition reaction. It is useful as a reagent.
  • the organic triol borate salt for example, after reacting boronic acid with a triol such as tris (hydroxylmethyl) ethane, a hydroxide or metal hydride such as sodium hydroxide or potassium hydroxide is reacted. Or a triol such as tris (hydroxylmethyl) ethane is reacted with an organic trialkoxyborate obtained by reacting an organolithium compound or an organomagnesium compound with trimethyl borate or triisopropyl borate, for example. Methods and the like are known (Angew. Chem. Int. Ed. 2008, 47,-928-931, WO 2008/09637).
  • An object of the present invention is to provide a method for producing an organic triol borate salt that can produce an organic triol borate salt having a functional group such as a carbonyloxy group, a carbonyl group, a hydroxyl group, or an amino group.
  • R is unsubstituted or a 1 to 4 ring aryl group having at least one of the following substituents (1) to (10), or unsubstituted or a substituent of (1) to (10) below.
  • Phenyl group represented by the following general formula [4] (Wherein R 7 is a halogen atom, an amino group, an alkoxycarbonyl group having 2 to 7 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms, or a halogenoalkyl having 1 to 6 carbon atoms)
  • R 7 is a halogen atom, an amino group, an alkoxycarbonyl group having 2 to 7 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms, or a halogenoalkyl having 1 to 6 carbon atoms
  • n 0 or 1
  • R 1 to R 6 each independently represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an alkoxycarbonyl group having 2 to 4 carbon atoms, where n is 0
  • R 1 represents an alkyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having 2 to 4 carbon atoms.
  • R 8 represents an alkyl group having 1 to 6 carbon atoms.
  • the present invention (I) a compound represented by the following general formula [1]; (In the formula, R and R 1 to R 6 are the same as above.) A compound represented by the following general formula [2]: (In the formula, R 8 is the same as above.) A process for producing an organic triol borate salt represented by the following general formula [3], characterized by reacting in an organic solvent in the presence of water and alkali metal hydroxide (MOH) (In the formula, R and R 8 are the same as above. M represents an alkali metal), And
  • R ′ represents the following (a), (b) or (c): (a) a phenyl group having at least one substituent of the following (1) to (6): (1) halogen atom, (2) amino group, (3) alkoxycarbonyl group having 2 to 7 carbon atoms, (4) halogenoalkyl group having 1 to 6 carbon atoms, (5) aminoalkyl group having 1 to 6 carbon atoms (6) an alkoxycarbonylalkyl group having 3 to 13 carbon atoms; (b) Unsubstituted or 2- to 4-ring aryl groups having at least one of the following substituents (1) to (10): (1) Phenyl group represented by the following general formula [4] (Wherein R 7 and k are the same as above), (2) halogen atom, (3) amino group, (4) alkoxycarbonyl group having 2 to 7 carbon atoms, (5) having 1 to 6 carbon atoms An alk
  • An alkoxycarbonylalkyl group, and (10) an alkoxyalkyl group having 2 to 12 carbon atoms, R 8 represents an alkyl group having 1
  • the organic triol borate salt of the present invention is a carbon-carbon bond forming reaction such as cross-coupling reaction, 1,4-addition reaction, carbon-nitrogen bond forming reaction, carbon-oxygen bond forming reaction, carbon-sulfur bond forming. It can be used for reaction etc., and can be made to react in an anhydrous organic solvent. Therefore, when the organic triol borate salt of the present invention is used as a reagent for an organic synthesis reaction such as a cross-coupling reaction or a 1,4-addition reaction, the reaction can be carried out efficiently.
  • the organic triol borate salt of the present invention is obtained for the first time by the production method of the present invention and has a carbonyloxy group, a carbonyl group, a hydroxyl group, and an amino group. Therefore, by using such a triol borate salt in the above reaction, it is possible to synthesize a compound having a carbonyloxy group, a carbonyl group, a hydroxyl group, or an amino group, which could not be produced by a conventional triol borate salt. It becomes.
  • R in the general formula [1] is unsubstituted or a 1-4 ring aryl group having at least one of the following substituents (1) to (10), or unsubstituted or the following substituents (1) to (10).
  • 1 to 2 aromatic heterocyclic groups having at least one of Substituent (1): phenyl group represented by the following general formula [4] (Wherein R 7 and k are the same as above).
  • Substituent (3) amino group.
  • Substituent (5) an alkoxy group having 1 to 6 carbon atoms.
  • Substituent (6) alkyl group having 1 to 6 carbon atoms, substituent (7): halogenoalkyl group having 1 to 6 carbon atoms, substituent (8): aminoalkyl group having 1 to 6 carbon atoms, substituent ( 9): an alkoxycarbonylalkyl group having 3 to 13 carbon atoms, and a substituent (10): an alkoxyalkyl group having 2 to 12 carbon atoms.
  • K in the general formula [4] usually represents an integer of 0 to 5, preferably an integer of 0 to 2, and 0 is particularly preferable.
  • halogen atom for R 7 in the general formula [4] examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • the alkoxycarbonyl group having 2 to 7 carbon atoms in R 7 in the general formula [4] may be any one having a linear, branched or cyclic alkoxy group, but has 2 to 4 carbon atoms.
  • the alkoxycarbonyl group is preferable.
  • the alkoxy group having 1 to 6 carbon atoms in R 7 in the general formula [4] may be linear, branched or cyclic, but preferably has 1 to 3 carbon atoms, specifically For example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-pentyloxy group, isopentyloxy group, sec-pentyloxy Group, tert-pentyloxy group, neopentyloxy group, n-hexyloxy group, isohexyloxy group, sec-hexyloxy group, tert-hexyloxy group, neohexyloxy group, cyclopropoxy group, cyclobutoxy group, etc. Can be mentioned.
  • the alkyl group having 1 to 6 carbon atoms in R 7 in the general formula [4] may be linear, branched or cyclic, but preferably has 1 to 3 carbon atoms, specifically For example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl Group, neopentyl group, 2-methylbutyl group, 1-ethylpropyl group, n-hexyl group, isohexyl group, sec-hexyl group, tert-hexyl group, neohexyl group, 2-methylpentyl group, 3-methylpentyl group, 1 , 2-dimethylbutyl group, 2,2-dimethylbutyl group, 1-eth
  • Examples of the halogenoalkyl group having 1 to 6 carbon atoms in R 7 in the general formula [4] include those in which part of the hydrogen atoms of the alkyl group having 1 to 6 carbon atoms in R 7 is substituted with a halogen atom. However, those in which some of the hydrogen atoms of the alkyl group having 1 to 3 carbon atoms are substituted with halogen atoms are preferred.
  • the halogen atoms may be the same or different and include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • trifluoromethyl group difluoromethyl group, fluoromethyl group, dichloromethyl group, chloromethyl group, dibromomethyl group, bromomethyl group, difluorochloromethyl group, pentafluoroethyl group, tetrafluoroethyl group, Fluoroethyl group, trifluorochloroethyl group, difluoroethyl group, fluoroethyl group, heptafluoropropyl group, hexafluoropropyl group, pentafluoropropyl group, tetrafluoropropyl group, trifluoropropyl group, difluoropropyl group, fluoropropyl group Chloropropyl group, bromopropyl group, perfluorobutyl group, perfluorohexyl group and the like.
  • Examples of the aminoalkyl group having 1 to 6 carbon atoms in R 7 in the general formula [4] include those in which part of the hydrogen atoms of the alkyl group having 1 to 6 carbon atoms in R 7 is substituted with an amino group. However, it is preferable that part of the hydrogen atoms of the alkyl group having 1 to 3 carbon atoms is substituted with an amino group. Specific examples include an aminomethyl group, an aminoethyl group, an aminopropyl group, an aminobutyl group, an aminopentyl group, and an aminohexyl group.
  • alkoxycarbonylalkyl group having 3 to 13 carbon atoms in R 7 in the general formula [4] a part of hydrogen atoms of the alkyl group having 1 to 6 carbon atoms as R 7 is substituted with an alkoxycarbonyl group.
  • alkoxycarbonyl group examples include the same as those described for the alkoxycarbonyl group having 2 to 7 carbon atoms in R 7 .
  • the alkoxycarbonylalkyl group is preferably an alkoxycarbonylalkyl group having 3 to 7 carbon atoms.
  • Examples of the alkoxyalkyl group having 2 to 12 carbon atoms in R 7 in the general formula [4] include those in which part of the hydrogen atoms of the alkyl group having 1 to 6 carbon atoms in R 7 is substituted with an alkoxy group.
  • Examples of the alkoxy group include the same groups as those described for the alkoxy group having 1 to 6 carbon atoms in R 7 .
  • the alkoxyalkyl group is preferably one having 2 to 4 carbon atoms.
  • Preferred specific examples of the general formula [4] include, for example, fluorophenyl group, chlorophenyl group, dichlorophenyl group, trichlorophenyl group, bromophenyl group, dibromophenyl group, tribromophenyl group, iodophenyl group, aminophenyl group, diamino Phenyl group, methoxycarbonylphenyl group, ethoxycarbonylphenyl group, n-propoxycarbonylphenyl group, n-butoxycarbonylphenyl group, n-pentyloxycarbonylphenyl group, n-hexyloxycarbonylphenyl group, methoxyphenyl group, ethoxyphenyl group N-propoxyphenyl group, n-butoxyphenyl group, n-pentyloxyphenyl group, n-hexyloxyphenyl group, methylphenyl group, ethy
  • halogen atom of the substituent (2) examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • alkoxycarbonyl group having 2 to 7 carbon atoms of the substituent (4) examples include the same alkoxycarbonyl groups as those described above for R 7 .
  • Examples of the alkoxy group having 1 to 6 carbon atoms of the substituent (5) include the same alkoxy groups as those described above for R 7 .
  • Examples of the alkyl group having 1 to 6 carbon atoms of the substituent (6) include the same alkyl groups as those described above for R 7 .
  • halogenoalkyl group having 1 to 6 carbon atoms of the substituent (7) examples include the same halogenoalkyl groups as those described above for R 7 .
  • Examples of the aminoalkyl group having 1 to 6 carbon atoms of the substituent (8) include the same aminoalkyl groups as those described above for R 7 .
  • alkoxycarbonylalkyl group having 3 to 13 carbon atoms of the substituent (9) examples include the same groups as the alkoxycarbonylalkyl group for R 7 described above.
  • alkoxyalkyl group having 2 to 12 carbon atoms of the substituent (10) examples include the same alkoxyalkyl groups as those described above for R 7 .
  • the unsubstituted 1 to 4 ring aryl group in R in the general formula [1] is a monocyclic aryl group or a condensed monocyclic aryl group. Specific examples thereof include a phenyl group and a naphthyl group. Group, anthracenyl group and pyrenyl group are mentioned, and a phenyl group or a pyrenyl group is preferable.
  • the above-mentioned unsubstituted 1-4-ring aryl group is the substituent ( 1) to (10) are usually 1 to 6, preferably 1 to 3, more preferably 1 to 2.
  • the substituent other than the positions adjacent to the 1st position is preferable to have the substituent other than the positions adjacent to the 1st position.
  • the aryl group is a phenyl group
  • the 3rd position It preferably has a substituent at the 4-position or 5-position.
  • a monocyclic (single ring) aryl group is preferable.
  • substituents (1) to (10) those selected from the substituents (2), (4), (5), (6) and (7) are preferable, and the substituents (2), ( Those selected from 4), (5) and (7) are more preferred.
  • substituents (2), ( Those selected from 4), (5) and (7) are more preferred.
  • substituents (2), ( Those selected from 4), (5) and (7) are more preferred.
  • Preferable specific examples of the 1 to 4 ring aryl group having at least one of the substituents (1) to (10) include, for example, a biphenyl group, a chlorophenylphenyl group, a dichlorophenylphenyl group, a bromophenylphenyl group, and a dibromophenylphenyl group.
  • Methoxycarbonylphenylphenyl group methoxyphenylphenyl group, trifluoromethylphenylphenyl group, chloro (methoxycarbonylphenylphenyl group, bromo (trifluoromethyl) phenylphenyl group, fluorophenyl group, chlorophenyl group, dichlorophenyl group, trichlorophenyl group , Bromophenyl group, dibromophenyl group, tribromophenyl group, iodophenyl group, aminophenyl group, diaminophenyl group, methoxycarbonylphenyl group, ethoxycarbonylphenyl group, n-propoxycarbonylphenyl group, n-butoxycarbonylphenyl group, n-pentyloxycarbonylphenyl group, n-hexyloxycarbonylphenyl group, methoxyphenyl group, ethoxyphen
  • the unsubstituted monocyclic (single ring) aromatic heterocyclic group in R in the general formula [1] is a 5- to 6-membered hetero atom such as a nitrogen atom, an oxygen atom or a sulfur atom. As described above, those having 1 to 4, more preferably 1 to 2 are preferable.
  • groups derived from 5-membered heterocycles having one heteroatom such as furan, thiophene, pyrrole, 2H-pyrrole, pyrroline, 2-pyrroline, pyrrolidine, such as oxazole, isoxazole, 1,3- A group derived from a 5-membered heterocycle having two heteroatoms such as oxazole, thiazole, isothiazole, 1,3-thiazole, imidazole, imidazoline, 2-imidazoline, imidazolidine, pyrazole, pyrazoline, 3-pyrazolin, prazolidine, For example, groups derived from 5-membered heterocycles having 3 heteroatoms such as furazane, triazole, thiadiazole, oxadiazole, etc., groups derived from 5-membered heterocycles having 4 heteroatoms such as tetrazole, such as pyran, 2H -Groups derived from 6-membered heterocycles having one
  • a group derived from a 6-membered heterocycle having 2 heteroatoms is preferable, a group derived from a 5-membered heterocycle having 1 heteroatom, and a group derived from a 5-membered heterocycle having 2 heteroatoms is more preferable.
  • furan, thiophene, pyrrole, 2H-pyrrole, oxazole, isoxazole, 1,3-oxazole, pyrazole-derived groups, and the like are particularly preferable.
  • the unsubstituted bicyclic aromatic heterocyclic group in R in the general formula [1] is a condensed monocyclic heterocyclic ring or an aromatic group such as benzene or naphthalene. And bicyclic heterocycles in which 2 to 3 saturated rings are condensed.
  • a group derived from a heterocycle having 2 heteroatoms such as a group derived from a heterocycle having 4 heteroatoms such as purine and pteridine, among which a 5-membered monocyclic heterocycle and benzene are Groups derived from fused bicyclic heterocycles are preferred, specifically benzofurans. , Isobenzofuran, 1-benzothiophene, 2-benzothiophene, indole, 3-indole, isoindole, and the like are preferable.
  • the 1- to 2-ring aromatic heterocyclic group having at least one substituent (1) to (10) is the above-described unsubstituted 1- to 2-ring aromatic heterocyclic group.
  • the cyclic group usually has 1 to 4, preferably 1 to 2, and more preferably 1 of the above substituents (1) to (10).
  • the substituent in order to avoid the influence of steric hindrance, when the bond to boron is in the 1-position, it is preferable to have the substituent at a position other than the positions adjacent to the 1-position.
  • the aromatic heterocyclic group is monocyclic In the case of a 5-membered ring, it preferably has a substituent at the 3-position or 4-position.
  • the aromatic heterocyclic group when it is a monocyclic 6-membered ring, it has a substituent at the 3-position, 4-position or 5-position. Is preferred.
  • a monocyclic (single ring) aromatic heterocyclic group is preferable.
  • substituents (1) to (10) those selected from the substituents (2), (4), (5), (6) and (7) are preferable, and are selected from the substituent (6). Is more preferable.
  • Preferred examples include phenylfuran, fluorofuran, chlorofuran, bromofuran, iodofuran, aminofuran, methoxycarbonylfuran, methoxyfuran, ethoxyfuran, methylfuran, ethylfuran, n-propylfuran, isopropylfuran, n-butylfuran.
  • Examples of the alkyl group having 1 to 3 carbon atoms in R 1 to R 6 in the general formula [1] include a methyl group, an ethyl group, an n-propyl group, and an isopropyl group, and a methyl group and an ethyl group are preferable.
  • a methyl group is more preferred.
  • Examples of the alkoxycarbonyl group having 2 to 4 carbon atoms in R 1 to R 6 in the general formula [1] include a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, and an isopropyloxycarbonyl group.
  • a methoxycarbonyl group an ethoxycarbonyl group is preferable, and an ethoxycarbonyl group is more preferable.
  • N in the general formula [1] represents 0 or 1, and 0 is preferable.
  • R 1 in the general formula [1] represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having 2 to 4 carbon atoms, and when n is 0, that is, in the general formula [1]
  • the compound shown forms a 5-membered boronic ester, it represents an alkyl group having 1 to 3 carbon atoms or an alkoxycarbonyl group having 2 to 4 carbon atoms.
  • n a methyl group, a methoxycarbonyl group or an ethoxycarbonyl group is preferable, a methyl group or an ethoxycarbonyl group is more preferable, a methyl group is particularly preferable, and when n is 1, a hydrogen atom is preferable.
  • R 2 to R 4 in the general formula [1] each independently represent a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an alkoxycarbonyl group having 2 to 4 carbon atoms, Preferably, a methyl group is more preferable.
  • R 5 and R 6 in the general formula [1] each independently represent a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an alkoxycarbonyl group having 2 to 4 carbon atoms, preferably a methyl group.
  • the compound represented by the general formula [1] include those represented by the following general formulas [1-1] to [1-14] (wherein R is the same as above), [1-1] to [1-2], [1-6] to [1-9], [1-11] to [1-12] (provided that R in the formula is the same as above) Among them, those represented by the general formula [1-2] (wherein R is the same as above) are particularly preferred.
  • R in the above general formulas [1-1] to [1-14] is a phenyl group, a pyrenyl group, a biphenyl group, a chlorophenylphenyl group, or dichlorophenylphenyl.
  • Examples of the alkyl group having 1 to 6 carbon atoms in R 8 represented by the general formula [2] include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert -Butyl, n-pentyl, isopentyl, sec-pentyl, tert-pentyl, neopentyl, 2-methylbutyl, 1-ethylpropyl, n-hexyl, isohexyl, sec-hexyl, tert -Hexyl group, neohexyl group, 2-methylpentyl group, 3-methylpentyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, methyl group An ethyl group is preferred.
  • Preferable specific examples of the compound represented by the general formula [2] include, for example, tris (hydroxylmethyl) ethane, tris (hydroxylmethyl) propane, tris (hydroxylmethyl) butane, tris (hydroxylmethyl) pentane, and tris (hydroxylmethyl).
  • Examples include hexane and tris (hydroxylmethyl) heptane, tris (hydroxylmethyl) ethane, tris (hydroxylmethyl) propane and the like are more preferable, and tris (hydroxylmethyl) ethane is particularly preferable.
  • R and R 8 in the general formula [3] the same thing can be mentioned as R 8 in R and the general formula [2] in the general formula [1], preferable are same include those.
  • M in the general formula [3] represents an alkali metal, and examples thereof include lithium, sodium, potassium, rubidium, cesium and the like, among which lithium, sodium, potassium and the like are preferable.
  • organic triol borate salt represented by the general formula [3] include those represented by the following general formulas [3-1] to [3-17] (wherein R is the same as above) And compounds represented by the general formulas [3-1] to [3-5] (wherein R is as defined above) are preferred, and among them, the general formulas [3-1] to [3-2] (Wherein R is the same as above) is more preferred.
  • organic triol borate salt represented by the general formula [3] include those in the general formulas [3-1] to [3-17] wherein R is a compound represented by the above general formula [1]. The case where it is the same as the specific example of R in a preferable specific example is mentioned.
  • an organic triol borate salt of the present invention the compound represented by the general formula [1] and the compound represented by the general formula [2] are combined in the presence of water and an alkali metal hydroxide (MOH). By reacting in an organic solvent, an organic triol borate salt represented by the above general formula [3] is produced.
  • MOH alkali metal hydroxide
  • the amount of the compound represented by the general formula [2] used in the production method of the present invention is usually 0.8 to 1.0 equivalent, preferably 0.9 to 0.9 equivalents relative to the compound represented by the general formula [1]. 1.0 equivalent.
  • the amount of water used in the production method of the present invention is 0.5 to 5 equivalents, preferably 1 to 5 equivalents, more preferably 2 to 5 equivalents, and still more preferably, relative to the compound represented by the general formula [1]. 3 to 4 equivalents.
  • Examples of the alkali metal hydroxide (MOH) include lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, etc. Among them, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc. Are preferable, and sodium hydroxide and potassium hydroxide are more preferable.
  • the amount used is usually 0.5 to 2 equivalents, preferably 0.8 to 1.1 equivalents, more preferably 0.9 to 1.0 equivalents, relative to the compound represented by the general formula [1]. .
  • the organic solvent examples include ethers such as diethyl ether, dimethoxyethane, diethoxyethane, tetrahydrofuran, and cyclopentylmethyl ether, and alcohols such as methanol, ethanol, and propanol.
  • ethers are preferable, and dioxane, dimethoxy, and the like.
  • Ethane, tetrahydrofuran and the like are preferable, and dioxane is particularly preferable. These may be used alone or in appropriate combination of two or more.
  • the amount of the organic solvent to be used is generally 0.1 to 100 mL, preferably 1 to 10 mL, relative to 1 mmol of the compound represented by the general formula [1].
  • the reaction temperature in the production method of the present invention is usually 10 to 90 ° C., preferably 30 to 60 ° C.
  • the reaction temperature may be appropriately set depending on the metal hydroxide used and other conditions.
  • sodium hydroxide is used as the alkali metal hydroxide, it is preferably 10 to 70 ° C.
  • the alkali metal hydroxide When potassium hydroxide is used, the temperature is preferably 50 to 90 ° C.
  • the reaction time is not particularly limited as long as the used raw material is consumed and the target organic triol borate salt is produced, but it is usually 3 to 24 hours, preferably 10 to 20 hours.
  • the production method of the present invention is, for example, a compound represented by the above general formula [1] and 0.8 to 1.0 equivalent of the above general formula with respect to the compound represented by the general formula [1].
  • the compound represented by [2] is 0.5 to 5 equivalents of water with respect to the compound represented by the general formula [1], and 0.5 to 2 with respect to the compound represented by the general formula [1].
  • the reaction may be carried out in the presence of 0 equivalent of an alkali metal hydroxide by reacting in the above ethers or alcohols in 0.1 to 100 mL at 10 to 90 ° C. for 3 to 24 hours. ]
  • the organic triol borate salt shown by this is manufactured.
  • the aminoalkyl group having 6 to 6 and the alkoxycarbonylalkyl group having 3 to 13 carbon atoms are the halogen atom, the alkoxycarbonyl group having 2 to 7 carbon atoms and the carbon number 1 described in the section of R 7 in the general formula [4]. Examples thereof are the same as those described above for a halogenoalkyl group having ⁇ 6, an aminoalkyl group having 1 to 6 carbon atoms and an alkoxycarbonylalkyl group having 3 to 13 carbon atoms.
  • the phenyl group having at least one substituent in (a) of R ′ includes (1) a halogen atom, (2) an amino group, and (3) an alkoxycarbonyl group having 2 to 7 carbon atoms. (4) at least one substituent selected from a halogenoalkyl group having 1 to 6 carbon atoms, (5) an aminoalkyl group having 1 to 6 carbon atoms, and (6) an alkoxycarbonylalkyl group having 3 to 13 carbon atoms.
  • substituents selected from (1) a halogen atom, (3) an alkoxycarbonyl group having 2 to 7 carbon atoms, and (4) a halogenoalkyl group having 1 to 6 carbon atoms It preferably has 1 to 6, preferably 1 to 3, more preferably 1 to 2 substituents.
  • phenyl group having at least one substituent in (a) of R ′ include, for example, a fluorophenyl group, a chlorophenyl group, a dichlorophenyl group, a trichlorophenyl group, a bromophenyl group, a dibromophenyl group, and a tribromophenyl group.
  • iodophenyl group aminophenyl group, diaminophenyl group, methoxycarbonylphenyl group, ethoxycarbonylphenyl group, n-propoxycarbonylphenyl group, n-butoxycarbonylphenyl group, n-pentyloxycarbonylphenyl group, n-hexyloxy Carbonylphenyl group, trifluoromethylphenyl group, pentafluoroethylphenyl group, chloromethylphenyl group, bromomethylphenyl group, aminomethylphenyl group, aminoethylphenyl group, aminopropylphenyl group, methoxy Carbonylmethylphenyl, methoxycarbonylethylphenyl, methoxycarbonylpropylphenyl, fluoro (trifluoromethyl) phenyl, chloro (trifluoromethyl) phenyl, bromo (trifluoromethyl) phenyl,
  • the 2- to 4-ring aryl group in (b) of R ′ in the general formula [3 ′] is unsubstituted or has at least one of the following substituents (1) to (10).
  • Substituent (1) phenyl group represented by the following general formula [4] (Wherein R 7 and k are the same as above).
  • Substituent (2) halogen atom
  • substituent (3) amino group
  • substituent (4) alkoxycarbonyl group having 2 to 7 carbon atoms
  • substituent (5) alkoxy group having 1 to 6 carbon atoms
  • substituted Group (6) alkyl group having 1 to 6 carbon atoms
  • substituent (7) halogenoalkyl group having 1 to 6 carbon atoms
  • substituent (8) aminoalkyl group having 1 to 6 carbon atoms
  • substituent (9 ) An alkoxycarbonylalkyl group having 3 to 13 carbon atoms
  • a substituent (10) an alkoxyalkyl group having 2 to 12 carbon atoms.
  • the unsubstituted bicyclic to tetracyclic aryl group in (b) of R ′ is a condensed monocyclic aryl group.
  • Specific examples thereof include a naphthyl group and an anthracenyl group.
  • the above-mentioned unsubstituted 2- to 4-ring aryl group The group usually has 1 to 6, preferably 1 to 3, and more preferably 1 to 2 substituents (1) to (10).
  • substituents (1) to (10) those selected from the substituents (2), (4), (5), (6) and (7) are preferable, and the substituents (2), (4) , (5) and (7) are more preferred.
  • 2- to 4-ring aryl group having at least one substituent are, for example, phenylnaphthyl group, fluoronaphthyl group, chloronaphthyl group, dichloronaphthyl group, bromonaphthyl group, iodonaphthyl group, fluoronaphthyl group.
  • fluoroanthracenyl group chloroanthracenyl group, dichloroanthracenyl group, bromoanthracenyl group, iodoanthracenyl group, fluoroanthracenyl group, fluoropyrenyl group, chloropyrenyl group, dichloropyrenyl group, bromopyrenyl group, Iodopyrenyl group, fluoropyrenyl group, trifluoromethylnaphthyl group, trifluoromethylanthracenyl group, trifluoromethylpyrenyl group, chloro (methoxycarbonyl) naphthyl group, chloro (methoxycarbonyl) anthracenyl group, Loro (methoxycarbonyl) pyrenyl group, methoxycarbonylnaphthyl group, ethoxycarbonylnaphthyl group, n-propoxycarbonylnap
  • R ′ in (b) is unsubstituted or a bicyclic to tetracyclic aryl group having at least one of the above substituents (1) to (10).
  • An unsubstituted 2- to 4-ring aryl group is preferred.
  • the 1- or 2-ring aromatic heterocyclic group in (c) of R ′ in the general formula [3 ′] is unsubstituted or has at least one of the following substituents (1) to (10).
  • Substituent (1) phenyl group represented by the following general formula [4] (Wherein R 7 and k are the same as above).
  • Substituent (2) halogen atom
  • substituent (3) amino group
  • substituent (4) alkoxycarbonyl group having 2 to 7 carbon atoms
  • substituent (5) alkoxy group having 1 to 6 carbon atoms
  • substituted Group (6) alkyl group having 1 to 6 carbon atoms
  • substituent (7) halogenoalkyl group having 1 to 6 carbon atoms
  • substituent (8) aminoalkyl group having 1 to 6 carbon atoms
  • substituent (9 ) An alkoxycarbonylalkyl group having 3 to 13 carbon atoms
  • a substituent (10) an alkoxyalkyl group having 2 to 12 carbon atoms.
  • the substituents (1) to (10) are the same as the substituents (1) to (10) in R in the general formula [1].
  • One or two aromatic heterocyclic groups having at least one of the above substituents (1) to (10) in R ′ of (c) in the general formula [3 ′] include the above general formula [ 1], the same as the 1- or 2-ring aromatic heterocyclic group having at least one substituent (1) to (10) in R, and the same preferable examples.
  • the unsubstituted 1-2 ring aromatic heterocyclic group in R ′ of (c) in the general formula [3 ′] is an unsubstituted 1-2 ring in R in the general formula [1]. And the same aromatic heterocyclic group.
  • Examples of the alkyl group for R 8 in the general formula [3 ′] include the same alkyl groups as those in the general formula [2].
  • Examples of the alkyl metal represented by M in the general formula [3 ′] include the same as M in the general formula [3].
  • organic triol borate salt represented by the general formula [3 ′] include, for example, those represented by the following general formulas [3′-1] to [3′-17] (provided that R ′ in the formula is the above) And the compounds represented by the general formulas [3′-1] to [3′-5] are preferable. Among them, the compounds represented by the general formulas [3′-1] to [3′-2] are preferable. Is more preferable.
  • R represents (a) a fluorophenyl group or a chlorophenyl group.
  • R is (a) fluorophenyl group, chlorophenyl group, dichlorophenyl group, trichlorophenyl group, bromophenyl group, dibromophenyl group, tribromophenyl group, iodophenyl group, methoxycarbonylphenyl group, ethoxycarbonylphenyl group.
  • the organic triol borate salt represented by the general formula [3 '] is produced, for example, by the method described in the method for producing an organic triol borate salt of the present invention.
  • the organic triol borate salt of the present invention as described above can be used for a reaction in an anhydrous organic solvent, it can be used, for example, a carbon-carbon bond forming reaction, a carbon-nitrogen bond forming reaction, a carbon-oxygen bond forming reaction, When used as a reagent for organic synthesis reactions such as carbon-sulfur bond forming reaction (especially cross-coupling reaction, addition reaction, etc.), the reaction can be carried out efficiently.
  • the organic triol borate salt of the present invention can have a carbonyloxy group, a carbonyl group, a hydroxyl group, and an amino group, a carbonyloxy group, a carbonyl group, a hydroxyl group, and an amino group, which have been difficult to introduce, can be easily obtained. Can be introduced.
  • the organic triol borate salt (substrate) of the present invention 0.1 to 3 times mol, preferably 0.5 to 2 times mol of organic halide and 0.01 to mol of the substrate.
  • -80% by weight of palladium catalyst (palladium metal is 0.0005-20% by weight with respect to the substrate) is added to the reaction solvent (in an amount of 1-20000 equivalents, preferably 10-700 equivalents with respect to the catalyst).
  • the desired product can be obtained by stirring reaction at about 20 ° C. to 200 ° C. for about 30 minutes to 100 hours.
  • the organic triol borate salt (substrate) of the present invention 0.1 to 3 times mol, preferably 0.5 to 2 times mol of the electron withdrawing group-substituted olefin compound and the substrate 0.01 to 80% by weight of rhodium catalyst (rhodium metal is 0.0.0005 to 20% by weight with respect to the substrate) and reaction solvent (1 to 20000 equivalents, preferably 10 to 700 equivalents to the catalyst).
  • rhodium catalyst rhodium metal is 0.0.0005 to 20% by weight with respect to the substrate
  • reaction solvent 1 to 20000 equivalents, preferably 10 to 700 equivalents to the catalyst.
  • the desired product can be obtained by stirring reaction at about 20 ° C. to 200 ° C. for about 30 minutes to 100 hours.
  • the copper-catalyzed amination reaction is carried out using the organic triol borate salt of the present invention, it may be carried out as follows.
  • the organic triol borate salt (substrate) of the present invention 0.1 to 3 times mol, preferably 0.5 to 2 times mol of the amine compound, and 0.01 to 3 mol of the substrate.
  • 80% by weight of copper catalyst copper metal is 0.0005 to 20% by weight based on the substrate
  • the reaction solvent 1 to 20000 equivalents, preferably 10 to 700 equivalents based on the catalyst
  • the target product is obtained by performing the same operation as in the case of the copper catalyst amination reaction except that various alcohols are used instead of the amine compound. Is obtained.
  • the target product is obtained by performing the same operation as in the case of the copper catalyst amination reaction except that various thioalcohols are used instead of the amine compound. Is obtained.
  • the organic triol borate salt (substrate) 0.1 to 3 times mol, preferably 0.5 to 2 times mol of the amine compound and 0.01 to 80% by weight with respect to the substrate.
  • % Of a copper catalyst copper metal in an amount of 0.0005 to 20% by weight based on the substrate
  • a reaction solvent an amount of 1 to 20000 equivalents, preferably 10 to 700 equivalents based on the catalyst
  • Example 1 Process for producing 3,5-dichlorophenyltriol borate sodium salt (1) Synthesis of 3,5-dichlorophenylboronic acid pinacol ester Di- ⁇ -methoxobis (1,5-cyclooctadiene) diiridium (I) (Wako Pure Chemical Industries, Ltd.) 1.66 mg (0.01 mmol%) 4,4′-di-tert-butyl-2,2′-bipyridine (dtbpy) (manufactured by ALDRICH) 1.34 mg (0.01 mmol) and hexane 5 ml were stirred at room temperature for 30 minutes.
  • triol borate salt 273 mg (1 mmol) of 3,5-dichlorophenylboronic acid pinacol ester, 120 mg (1 mmol) of tris (hydroxylmethyl) ethane (manufactured by Wako Pure Chemical Industries, Ltd.), 40 mg (1 mmol) of sodium hydroxide Then, 5 ml of dioxane and 54 ⁇ l (3 mmol) of water were placed in a 25 ml branch flask and reacted at 30 ° C. with stirring for 16 hours. After the reaction, 16 ml of hexane was added to precipitate the reaction product, and the solid was filtered and washed.
  • Example 2 Difference in reaction efficiency due to difference in reaction temperature Except that the reaction temperature of Example 1 was changed from 30 ° C to 60 ° C, an experiment was conducted in the same manner as in Example 1 to obtain a triol borate salt. As a result, the yield was 76%.
  • the reaction conditions and yield of the reaction are shown in Table 1.
  • the physical property data was the same as in Example 1.
  • Example 3 Difference in reaction efficiency due to difference in amount of sodium hydroxide The experiment was conducted in the same manner as in Example 2 except that the amount of sodium hydroxide used was 36 mg (0.9 mmol) to obtain a triol borate salt. It was. As a result, the yield was 72%. The reaction conditions and yield of the reaction are shown in Table 1. The physical property data was the same as in Example 1.
  • Example 4 Difference in reaction efficiency due to difference in amount of water used Except that the amount of water used was changed to 17 ⁇ l (1 mmol), an experiment was performed in the same manner as in Example 3 to obtain a triol borate salt. As a result, the yield was 27%.
  • the reaction conditions and yield of the reaction are shown in Table 1.
  • the physical property data was the same as in Example 1.
  • Example 5 Difference in reaction efficiency due to difference in solvent An experiment was performed in the same manner as in Example 1 except that tetrahydrofuran (THF) was used instead of dioxane as a solvent to obtain a triol borate salt. As a result, the yield was 48%.
  • THF tetrahydrofuran
  • the reaction conditions and yield of the reaction are shown in Table 1.
  • the physical property data was the same as in Example 1.
  • Example 6 Difference in reaction efficiency due to difference in solvent Except that 1,2-dimethoxyethane (DME) was used instead of dioxane as a solvent, an experiment was conducted in the same manner as in Example 1 to obtain a triol borate salt. . As a result, the yield was 46%.
  • the reaction conditions and yield of the reaction are shown in Table 1.
  • the physical property data was the same as in Example 1.
  • triol borate salt can be obtained, and that the triol borate salt can be obtained in a high yield when the amount of water used is 3 equivalents of the starting material. From Examples 5 and 6, it was found that even when tetrahydrofuran other than dioxane or 1,2-dimethoxyethane was used as a solvent, the target triol borate salt was obtained although the yield was reduced.
  • Examples 7 to 21 Method for producing triol borate salt using various starting materials Pinacol boronic acid having various substituents described in Table 2 instead of pinacol 3,5-dichlorophenylboronic acid as starting material of Example 1
  • An experiment was conducted in the same manner as in Example 1 except that the triol borate salt was obtained.
  • the experiment was conducted at a reaction temperature of 60 ° C. The respective yields are shown in Table 2.
  • Examples 22 to 26 Method for producing triol borate potassium salt using various starting materials Instead of pinacol 3,5-dichlorophenylboronate in Example 1, pinacol boronate having various substituents described in Table 3 was used. An experiment was performed in the same manner as in Example 1 except that 0.9 mmol of potassium hydroxide was used instead of 1.0 mmol of sodium hydroxide and the reaction temperature was 90 ° C., to obtain potassium triol borate. The respective yields are shown in Table 3.
  • triol borate salts having a phenyl group having a substituent at the 3-position or 4-position when the bond to boron is in the 1-position can be easily obtained. It was found that it could be manufactured.
  • Example 27 Method for producing pyrenyltriol borate potassium salt (1) Synthesis of pyrenyl pinacol boronic acid ester (CH boronation method) 1.66 mg of di- ⁇ -methoxobis (1,5-cyclooctadiene) diiridium (I) ([Ie (OMe) (cod)] 2 , manufactured by Wako Pure Chemical Industries, Ltd.) (0.1 mol to the reaction substrate) %; 0.01 mmol), 4,4′-di-tert-butyl-2,2′-bipyridine (dtbpy) (Aldrich) 1.34 mg (0.1 mol% relative to the reaction substrate; 0.01 mmol), and cyclohexane 5 ml was weighed into a 25 ml branch flask and stirred at room temperature for 30 minutes.
  • CH boronation method 1.66 mg of di- ⁇ -methoxobis (1,5-cyclooctadiene) diiridium (I
  • triol borate salt Yield 89%).
  • the reaction formula is described below.
  • the physical property data of the obtained triol borate salt are shown below.
  • Example 28 Method for producing 3,5-dimethyl-4-isoxazolyltriol borate potassium salt (1) Synthesis of 3,5-dimethyl-4-isoxazolylboronic acid pinacol ester 4-iodo-3,5-dimethylisoxazole (manufactured by Tokyo Chemical Industry Co., Ltd.) (3.56 g) in dioxane (30 ml) , 16 mmol), Triethylamine (Wako Pure Chemical Industries, Ltd.) (6.68 ml, 48 mmol), Dichlorobis (triphenylphosphine) palladium (II) (Wako Pure Chemical Industries, Ltd.) (0.56 g, 0.8 mmol) 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (manufactured by Wako Pure Chemical Industries, Ltd.) (4.06 ml, 24 mmol) was added and stirred for 3 hours under reflux.
  • Triethylamine Wiethylamine
  • the target product was extracted with diethyl ether and saturated brine, and treated with magnesium sulfate. Thereafter, it was isolated and purified by column chromatography to obtain 1- (1H-2-pyrrolylphenyl) ethanone (yield 99% or more). From this result, it was found that the coupling reaction can be advanced with high efficiency by using the triol borate salt of the present invention obtained by the production method of the present invention.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

Cette invention a pour objectif de pourvoir à un procédé de production d'un sel de triolborate organique, le procédé étant capable de produire un sel de triolborate organique qui contient des groupes fonctionnels tels qu'un groupe carbonyloxy, un groupe carbonyle, un groupe hydroxyle, et un groupe amino. Pour ce faire, la présente invention consiste en : (I) un procédé de production d'un sel de triolborate organique représenté par la formule générale [3] [3] caractérisé par la réaction d'un composé représenté par la formule générale [1] [1] avec un composé représenté par la formule générale [2] [2] dans un solvant organique en présence d'eau et d'un hydroxyde de métal alcalin (MOG) ; et (II) un sel de triolborate organique représenté par la formule générale (3'). [3']
PCT/JP2012/062906 2011-12-02 2012-05-21 Procédé de production d'un sel de triolborate organique WO2013080583A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2013547009A JP5928479B2 (ja) 2011-12-02 2012-05-21 有機トリオールボレート塩の製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2011-264180 2011-12-02
JP2011264180 2011-12-02

Publications (1)

Publication Number Publication Date
WO2013080583A1 true WO2013080583A1 (fr) 2013-06-06

Family

ID=48535068

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2012/062906 WO2013080583A1 (fr) 2011-12-02 2012-05-21 Procédé de production d'un sel de triolborate organique

Country Status (2)

Country Link
JP (1) JP5928479B2 (fr)
WO (1) WO2013080583A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103724282A (zh) * 2014-01-09 2014-04-16 于海波 一种医药中间体喹唑啉衍生物的合成方法
CN104591938A (zh) * 2015-01-29 2015-05-06 杨海霞 一种医药中间体二芳基甲烷类化合物的合成方法
CN105111057A (zh) * 2015-09-08 2015-12-02 张涛 一种芳基烯酮类化合物的合成方法
JP2017095363A (ja) * 2015-11-18 2017-06-01 国立大学法人北海道大学 新規トリフルオロメチル化剤及びそれを用いたトリフルオロメチル基含有化合物の製造方法
WO2019142854A1 (fr) * 2018-01-17 2019-07-25 株式会社神鋼環境ソリューション Procédé de synthèse de composé ester d'acide boronique, et sel de sodium de composé ester d'acide boronique et son procédé de synthèse
WO2019200520A1 (fr) * 2018-04-17 2019-10-24 南通纺织丝绸产业技术研究院 Application de n-butyllithium dans la catalyse d'hydroboration de composés carbonylés et de borane

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008093637A1 (fr) * 2007-01-29 2008-08-07 Wako Pure Chemical Industries, Ltd. Réactif pour une réaction de synthèse organique contenant un sel borate de triol organique

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK2522658T3 (en) * 2010-01-04 2018-11-19 Nippon Soda Co NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS AND AGRICULTURAL / Horticulture Bactericidal Agents
JP2012254970A (ja) * 2011-05-13 2012-12-27 Ishihara Sangyo Kaisha Ltd トリフルオロメチルピリジントリオールボレート塩

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008093637A1 (fr) * 2007-01-29 2008-08-07 Wako Pure Chemical Industries, Ltd. Réactif pour une réaction de synthèse organique contenant un sel borate de triol organique

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LI, GAO-QIANG ET AL.: "Direct Conversion of Pinacol Arylboronic Esters to Aryl Triolborates", CHEMISTRY LETTERS, vol. 40, no. 7, 4 June 2011 (2011-06-04), pages 702 - 704, XP003031946 *
Y.YAMAMOTO ET AL.: "Cyclic Triolborates: Air- and Water-Stable Ate Complexes of Organoboronic Acids", ANGEWANDTE CHEMIE, vol. 47, no. 5, 2008, pages 928 - 931, XP055072727 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103724282A (zh) * 2014-01-09 2014-04-16 于海波 一种医药中间体喹唑啉衍生物的合成方法
CN104591938A (zh) * 2015-01-29 2015-05-06 杨海霞 一种医药中间体二芳基甲烷类化合物的合成方法
CN105111057A (zh) * 2015-09-08 2015-12-02 张涛 一种芳基烯酮类化合物的合成方法
JP2017095363A (ja) * 2015-11-18 2017-06-01 国立大学法人北海道大学 新規トリフルオロメチル化剤及びそれを用いたトリフルオロメチル基含有化合物の製造方法
WO2019142854A1 (fr) * 2018-01-17 2019-07-25 株式会社神鋼環境ソリューション Procédé de synthèse de composé ester d'acide boronique, et sel de sodium de composé ester d'acide boronique et son procédé de synthèse
CN111801335A (zh) * 2018-01-17 2020-10-20 株式会社神钢环境舒立净 亚硼酸酯化合物的合成方法、亚硼酸酯化合物的钠盐及其合成方法
JPWO2019142854A1 (ja) * 2018-01-17 2021-03-25 株式会社神鋼環境ソリューション ボロン酸エステル化合物の合成方法、ボロン酸エステル化合物のナトリウム塩及びその合成方法
JP7039624B2 (ja) 2018-01-17 2022-03-22 株式会社神鋼環境ソリューション ボロン酸エステル化合物の合成方法、ボロン酸エステル化合物のナトリウム塩及びその合成方法
WO2019200520A1 (fr) * 2018-04-17 2019-10-24 南通纺织丝绸产业技术研究院 Application de n-butyllithium dans la catalyse d'hydroboration de composés carbonylés et de borane

Also Published As

Publication number Publication date
JP5928479B2 (ja) 2016-06-01
JPWO2013080583A1 (ja) 2015-04-27

Similar Documents

Publication Publication Date Title
JP5928479B2 (ja) 有機トリオールボレート塩の製造方法
AU2008211047B2 (en) Reagent for organic synthesis reaction containing organic triol borate salt
Xia et al. Iron-catalyzed reductive cyclization reaction of 1, 6-enynes for the synthesis of 3-acylbenzofurans and thiophenes
CN110536884A (zh) Mcl-1抑制剂的合成
KR20190093198A (ko) 아릴 하이드로카본 수용체 조절자
CN102584735A (zh) 一种异噁唑类化合物的制备方法
Clapham et al. Trifluoromethyl-substituted pyridyl-and pyrazolylboronic acids and esters: synthesis and Suzuki–Miyaura cross-coupling reactions
Bumagin et al. Effective bimetallic composite catalysts for the synthesis of arylated furans and thiophenes in aqueous media
Zhai et al. Effective laboratory-scale preparation of axitinib by two CuI-catalyzed coupling reactions
CN106146518A (zh) 一种布鲁顿酪氨酸激酶抑制剂中间体及其制备方法
CN103483279B (zh) 一种1,4-二取代三氮唑化合物的制备方法
Muñoz‐Torres et al. “Back‐to‐Front” Indole and Carbazole Synthesis from N, N‐Bis‐(2‐bromoallyl) amines by Combining Carbolithiation Reactions with Gold‐Catalysis
NZ545838A (en) Process for the preparation of N-amino substituted heterocyclic compounds
Srikrishna et al. Synthesis of novel substituted 3-(4-((1 H-benzo [d] imidazol-2-ylthio) methyl)-1-phenyl-1 H-pyrazol-3-yl)-2 H-chromen-2-ones: various approaches
Chen et al. Iodine-induced regioselective direct alkylation of azoles via in situ formed alkyliodide
Dou et al. 3D Luminescent Copper (I) Iodide Coordination Polymer Based on Cu4I4 Clusters and an Ethyl‐bridging Bis (triazole) Ligand
CN105481790B (zh) 一类含磺酰胺的二氢噻唑酮类化合物及其药物组合物和用途
Bratanovici et al. Design and synthesis of novel ditopic ligands with a pyrazole ring in the central unit
Kudelko et al. Study on the synthesis of novel 5-substituted 2-[2-(pyridyl) ethenyl]-1, 3, 4-oxadiazoles and their acid–base interactions
Demidov et al. Oxidative SN H-alkoxylation of 1, 3, 7-triazapyrenes
Yang et al. Manganese‐Mediated Reductive Alkylation of Thiazolyl‐Phosphonium Salts
CN109438448A (zh) 一种吲哚并七元环化合物及其制备方法和用途
Clapham et al. New Pyrimidylboronic Acids and Functionalized Heteroarylpyrimidines by Suzuki Cross‐Coupling Reactions
CN111333672B (zh) 一种固醇调控元件结合蛋白和酸性核质dna结合蛋白-1抑制剂及其制备方法和应用
Kostyuchenko et al. New approach to the synthesis of 2, 2': 5', 2''-terthiophene-5, 5''-and 2, 2': 5', 2'': 5'', 2'''-quaterthiophene-5, 5'''-dicarboxylic acids

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: 12852968

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2013547009

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12852968

Country of ref document: EP

Kind code of ref document: A1