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WO2018109872A1 - Dérivé de cyclopenténone et son procédé de production - Google Patents

Dérivé de cyclopenténone et son procédé de production Download PDF

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Publication number
WO2018109872A1
WO2018109872A1 PCT/JP2016/087257 JP2016087257W WO2018109872A1 WO 2018109872 A1 WO2018109872 A1 WO 2018109872A1 JP 2016087257 W JP2016087257 W JP 2016087257W WO 2018109872 A1 WO2018109872 A1 WO 2018109872A1
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group
substituent
alkyl
compound
formula
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English (en)
Japanese (ja)
Inventor
笠井　均
良卓 小関
尭明 神島
利之 野中
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Fromseeds Corp
Tohoku University NUC
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Fromseeds Corp
Tohoku University NUC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
    • C07C209/14—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of hydroxy groups or of etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/16—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings other than six-membered aromatic rings
    • C07C211/17—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings other than six-membered aromatic rings containing only non-condensed rings
    • 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
    • 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
    • C07C45/65—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 splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/647—Unsaturated compounds containing a keto groups being part of a ring having unsaturation outside the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
    • C07C49/707—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups a keto group being part of a three- to five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups

Definitions

  • the present invention relates to a novel cyclopentenone derivative and a method for producing the same.
  • Prostaglandins are bioactive lipids biosynthesized from arachidonic acid in vivo.
  • Prostaglandins have prostanoic acid as the basic skeleton, and there are different molecular species such as prostaglandins -E 2 , -I 2 , -D 2 , -F 2 ⁇ depending on the structure of the five-membered ring part and side chain part. To do.
  • Prostaglandins and their derivatives show various physiological effects such as lowering blood pressure, lowering intraocular pressure, myometrial contraction, smooth muscle dilation, vasodilation, and platelet aggregation inhibition, improving peripheral circulatory disturbances, induction of labor and labor, glaucoma It is widely used as a medicine for the treatment of gastric ulcer and duodenal ulcer.
  • Non-patent Document 1 In order to produce prostaglandins and derivatives thereof, the Cory lactone method (Patent Document 1), the conjugate addition reaction method (Non-Patent Document 1), the three-component linking method (Non-Patent Document 2), and the two-component linking method have been used so far (Non-patent Document 3 and Patent Document 2) have been developed. These methods have the problem that the number of steps is large and the efficiency is low.
  • an exo-enone compound (c) is used as an important synthetic intermediate for prostaglandins (Non-patent Document 4).
  • an epoxy alcohol (a) obtained by epoxidation reaction of divinyl carbinol is used as a starting material, and ⁇ -hydroxyketone (b) is led through several steps.
  • an exo-enone compound (c) is obtained by elimination reaction.
  • the ⁇ -hydroxyketone (b) since the ⁇ -hydroxyketone (b) is used, the three hydroxyl groups in the intermediate (b) must be selectively protected.
  • the two-component connection method has a complicated manufacturing process.
  • the TBS (tert-butyldimethylsilyl) protecting group in the intermediate (c) is expensive, and there is a concern about environmental problems.
  • the exo-enone intermediate (c) is unstable, the two-component linking method using the intermediate (c) is industrially inefficient.
  • the method for producing a prostaglandin derivative requires selective protection and deprotection for each of the three hydroxyl groups of the intermediate (b). Therefore, it is difficult to isolate the product and the number of reaction steps is large, resulting in a problem that the production cost of the target product is increased.
  • the reaction process depending on the unstable intermediate (c) is industrially disadvantageous, but the development of an intermediate that can be used simply, inexpensively and industrially is still insufficient.
  • the object of the present invention is to solve the above-mentioned drawbacks or problems in the prior art, and to provide an industrially preferable novel synthetic intermediate in the production of prostaglandin derivatives and the like.
  • Another object of the present invention is to provide a method for producing a novel synthetic intermediate in the production of economically preferable prostaglandin derivatives and the like suitable for industrialization.
  • the present inventors have earnestly studied cyclopentenone derivatives that can be used as synthetic intermediates such as prostaglandin derivatives and methods for producing the same.
  • the present inventors succeeded in producing 4-hydroxy-2-hydroxymethyl-2-cyclopentenone easily by hydrothermal reaction from a monosaccharide.
  • the present inventors made dietherification using this 4-hydroxy-2-hydroxymethyl-2-cyclopentenone as a starting material, and then conducted an amination reaction on this diether compound. It has been found that the cyclopentenone compound represented by the following general formula (I) can be produced by the progress of the reaction. Based on this finding, the present inventors have completed the present invention.
  • R 4 , R 5 and R 6 are each an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted arylalkyl.
  • R 4 , R 5 and R 6 are each an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted arylalkyl.
  • R 2 and R 3 are the same or different and each is an alkyl group which may have a substituent.
  • R 1 may have an alkyl group which may have a substituent, an alkoxyalkyl group which may have a substituent, an aryloxyalkyl group which may have a substituent, or a substituent.
  • R 1 is Methoxymethyl group, methoxyethyl group, methoxypropyl group, methoxyisopropyl group, methoxybutyl group, Ethoxymethyl group, ethoxyethyl group, ethoxypropyl group, ethoxyisopropyl group, ethoxybutyl group, Propoxymethyl group, propoxyethyl group, propoxypropyl group, propoxyisopropyl group, propoxybutyl group, Isopropoxymethyl group, isopropoxyethyl group, isopropoxypropyl group, isopropoxyisopropyl group, isopropoxybutyl group, Butoxymethyl
  • the R 1 is an optionally substituted phenyloxy C 1 -C 6 alkyl group, and the R 2 and R 3 are the same or different and each has a substituent.
  • R 1 is an optionally substituted benzyloxy C 1 -C 6 alkyl group, and R 2 and R 3 are the same or different and each has a substituent.
  • the method of the present invention provides a novel industrial production method for cyclopentenone compounds.
  • 4-hydroxy-2-hydroxymethyl-2-cyclopentenone is converted into a diether in which an ether protecting group is introduced into its two hydroxyl groups, and the resulting diether is subjected to mild conditions. And succeeded in easily obtaining the target cyclopentenone compound in only two steps.
  • the target cyclopentenone compound can be easily produced on an industrial scale with high yield and efficiency.
  • the method of the present invention can provide a novel compound, a cyclopentenone compound, which is useful as a pharmaceutical and its intermediate.
  • novel compounds (formula (I), formula (II) and formula (III)) obtained by the method of the present invention are expected to be useful as intermediates and reagents for pharmaceuticals.
  • Alkyl group means, unless otherwise specified, a saturated aliphatic hydrocarbon group, for example, a linear or branched alkyl group having 1 to 20 carbon atoms, such as a methyl group, an ethyl group, a propyl group, an isopropyl group.
  • a group of C 1 -C 6 alkyl is preferable.
  • Preferred examples of C 1 -C 6 alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl or hexyl.
  • Alkoxy group means an (alkyl group) -O- group (wherein the alkyl group has the same meaning as described above). For example, a C 1 -C 10 alkoxy group, preferably a C 1 -C 6 alkoxy group can be mentioned.
  • C 1 -C 10 alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy, hexyl Including, but not limited to, an oxy group, an isohexyloxy group, a heptyloxy group, an octyloxy group, a nonyloxy group, a decyloxy group, and the like.
  • C 1 -C 6 alkoxy examples include methoxy group, ethoxy group, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, hexyloxy and the like. It is not limited.
  • alkoxyalkyl group means an “alkyl group” substituted with an “alkoxy group” (wherein the alkoxy group and the alkyl group have the same meaning as described above). For example, C 1 ⁇ C 6 alkoxy C 1 ⁇ C 6 alkyl group.
  • alkoxyalkoxyalkyl group means an “alkyl group” substituted with an “alkoxyalkoxy group” (wherein the alkoxy group and the alkyl group have the same meaning as described above). For example, C 1 ⁇ C 6 alkoxy C 1 ⁇ C 6 alkoxy C 1 ⁇ C 6 alkyl group.
  • alkylthioalkyl group means an alkyl group substituted with “(alkyl group) -S—” (wherein the alkyl group has the same meaning as described above).
  • a C 1 -C 10 alkyl-S—C 1 -C 10 alkyl group preferably a C 1 -C 6 alkyl-S—C 1 -C 6 alkyl group may be mentioned.
  • C 1 -C 6 alkyl-S—C 1 -C 6 alkyl examples include: Methylthiomethyl group, An ethylthiomethyl group, Propylthiomethyl group, Isopropylthiomethyl group, Butylthiomethyl group, sec-butylthiomethyl group, Isobutylthiomethyl group, tert-butylthiomethyl group, pentylthiomethyl group or hexylthiomethyl group, Methylthioethyl group, Ethylthioethyl group, Propylthioethyl group, Isopropylthioethyl group, Butylthioethyl group, sec-butylthioethyl group, Examples thereof include an isobutylthioethyl group, a tert-butylthioethyl group, a pentylthioethyl group, and a hexylthio
  • aryl refers to monocyclic or bicyclic aromatic hydrocarbon radical, preferably a phenyl group, C 6 ⁇ 10 aryl group such as phenyl or naphthyl, more preferably, is a phenyl group .
  • Arylalkyl group means an alkyl group substituted by an aryl group. Preferably, it is a phenyl C 1 -C 6 alkyl group. Examples of phenyl C 1 -C 6 alkyl groups are benzyl group, 1-phenylethyl group, 2-phenylethyl group, 3-phenylpropyl group, 4-phenylbutyl group, 5-phenylpentyl group, 6-phenylhexyl group. However, it is not limited to these.
  • aryloxyalkyl group means an alkyl group substituted with “(aryl group) -O—” (wherein the alkyl group and the aryl group have the same meaning as described above).
  • C 6 ⁇ 10 aryl group -O-C 1 ⁇ C 6 alkyl group examples include C 6 ⁇ 10 aryl -O-C 1 ⁇ C 6 alkyl group, a phenyl oxymethyl group, 1-phenyl-oxyethyl group, 2-phenyloxyethyl group, 3-phenyl propyl group, 4-phenyloxy-butyl Group, 5-phenyloxypentyl group, 6-phenyloxyhexyl group and the like, but is not limited thereto.
  • Arylalkyloxyalkyl group means an alkyl group substituted with “(arylalkyl-O—” (wherein the alkyl group and arylalkyl group have the same meanings as described above), for example, phenyl C 1 ⁇ C 6 alkyloxy group, and the like.
  • phenyl C 1 ⁇ C 6 alkyloxy C 1 ⁇ C 6 alkyl group examples include, but are not limited to, oxymethyl group, 3-phenylpropyloxymethyl group, 4-phenylbutyloxymethyl group, 5-phenylpentyloxymethyl group, 6-phenylhexyloxymethyl group, and the like.
  • R 4 , R 5 and R 6 are each an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted arylalkyl.
  • the “alkoxyalkyl group” in the “alkoxyalkyl group substituted with a silyl group represented by the general formula (1)” has the same meaning as described above.
  • substituent It may have a substituent "means that it may have a substituent or may be unsubstituted. In the case of having a substituent, the substituent may have 1 to 5, preferably 1 to 3, at the substitutable position. When the number of substituents is 2 or more, each substituent is Each may be the same or different.
  • substituents include an alkyl group, an alkoxy group, a halogen atom, a cyano group, and a nitro group.
  • Preferred examples of the substituent include a C1-C6 alkyl group, a C1-C6 alkoxy group, and a halogen.
  • R 1 in the compound represented by the formula (I) include a methyl group, an ethyl group, a propyl group, a normal butyl group, a methoxymethyl group, a methylthiomethyl group, a phenyldimethylsilylmethoxymethyl group, and a benzyloxymethyl group.
  • halogen atom refers to a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc., preferably a fluorine atom and a chlorine atom.
  • Compound (II) of the present invention can be produced, for example, by the method shown below or a method analogous thereto. (J. Am. Chem. Soc., 1977. 99 1275).
  • the desired compound (II) can be obtained by reacting the compound of formula (ii) with R 1 -L in the presence of a base in a suitable solvent.
  • the raw material compound (ii) can be produced based on the method described in Japanese Patent No. 5777984.
  • R 1 has an alkyl group which may have a substituent, an alkoxyalkyl group which may have a substituent, an alkoxyalkoxyalkyl group which may have a substituent, and a substituent.
  • Optionally substituted arylalkyloxyalkyl group or formula (i) (In the formula, R 4 , R 5 and R 6 are each an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted arylalkyl.
  • L represents a halogen such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • R 1 -L is known per se or can be produced based on known literature.
  • R 1 -L include an optionally substituted alkyl halide, an optionally substituted alkoxyalkyl halide, an optionally substituted alkoxyalkoxyalkyl halide, and a substituent.
  • alkylthioalkyl halide which may have a substituent, an aryl halide which may have a substituent, an arylalkyl halide which may have a substituent, an aryloxyalkyl halide which may have a substituent,
  • Optionally substituted arylalkyloxyalkyl halide or formula (i) (In the formula, R 4 , R 5 and R 6 are each an optionally substituted alkyl group, an optionally substituted aryl group, or an optionally substituted arylalkyl.
  • alkyl halide examples include C 1 -C 6 alkyl halide.
  • C 1 -C 6 alkyl halide means a linear or branched alkyl halide having 1 to 6 carbon atoms.
  • Examples of the C 1 -C 6 alkyl halide include methyl chloride, ethyl chloride, propyl chloride, isopropyl chloride, butyl chloride, sec-butyl chloride, isobutyl chloride, tert-butyl chloride, pentyl chloride, 1-methylbutyl chloride, 2 -Methylbutyl chloride, 3-methylbutyl chloride, 1-ethylpropyl chloride, 1,1-dimethylpropyl chloride, 1,2-dimethylpropyl chloride, 2,2-dimethylpropyl chloride, hexyl chloride, 1-methylpentyl chloride, 2-methylpentyl chloride, 3-methylpentyl chloride, 4-methylp
  • base examples of the base used include organic bases and inorganic bases.
  • Organic bases include, but are not limited to, triethylamine, N, N-diisopropylethylamine (DIPEA), pyridine, 4-dimethylaminopyridine (DMAP), n-butyllithium, potassium tert-butoxide.
  • Inorganic bases include, but are not limited to, sodium hydride, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or cesium carbonate. The amount of the base used is preferably 2 equivalents or more of the raw material compound.
  • a range of usually 2.0 to 50.0 equivalents with respect to 1 mol of the raw material compound can be exemplified, but a range of preferably 5.0 to 20.0 equivalents, more preferably 5.0. It is in the range of ⁇ 10.0 equivalents.
  • the reaction of the present invention is preferably carried out in the presence of a solvent.
  • the solvent in the reaction of the present invention may be any solvent as long as the reaction proceeds.
  • the solvent include aromatic hydrocarbon derivatives, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, ethers, alcohols, nitriles, amides, alkyl ureas, sulfoxides, sulfones, and ketones. , Carboxylic acid esters, carboxylic acids, aromatic heterocycles, and combinations of two or more thereof in a mixed solvent system.
  • Preferred examples of the solvent system used include toluene, xylene, chlorobenzene, dichlorobenzene, nitrobenzene, dichloromethane, tetrahydrofuran (THF), diisopropyl ether, dibutyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, methanol, ethanol , Propanol, 2-propanol, butanol, acetonitrile, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N, N′-dimethylimidazolidinone (DMI) ), Dimethyl sulfoxide (DMSO), sulfolane, and solvent systems comprising them, more preferably toluene, xylene, chlorobenzene, dichlorobenzene, nitrobenzene.
  • THF te
  • the amount of the solvent used to form the solvent system is not particularly limited as long as the reaction system can be sufficiently stirred. From the viewpoints of reactivity, suppression of by-products and economic efficiency, the amount of solvent is usually 0 (zero) to 10.0 L (liter), preferably 0.01 to 1 mol per 1 mol of the raw material (ii). A range of 10.0 L, more preferably 0.1 to 5.0 L, and still more preferably 0.2 to 3.0 L can be exemplified.
  • reaction temperature is not particularly limited. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it is usually in the range of 10 ° C to 100 ° C, preferably 40 ° C to 95 ° C, more preferably 50 ° C to 95 ° C, more preferably 55 ° C to 90 ° C. Can be illustrated.
  • reaction time is not particularly limited. From the viewpoint of yield, by-product suppression, economic efficiency, etc., the range of usually 0.5 hours to 48 hours, preferably 0.5 hours to 24 hours, more preferably 1 hour to 12 hours may be exemplified. it can.
  • Compound (III) of the present invention can be produced by a known method or a method analogous thereto (see Chem. Commun., 2016, 52, 7596-7599).
  • the target compound of formula (III) can be obtained by reacting the compound of formula (II) with HNR 2 R 3 in the presence of a base in an appropriate solvent.
  • HNR 2 R 3 (HNR 2 R 3 ) R 2 and R 3 are the same or different and each is an alkyl group which may have a substituent. HNR 2 R 3 is known per se or can be produced based on known literature.
  • alkyl group is a saturated aliphatic hydrocarbon group, for example, a linear or branched alkyl group having 1 to 20 carbon atoms, for example, a methyl group, an ethyl group, a propyl group, an isopropyl, unless otherwise specified.
  • a group of C 1 -C 6 alkyl is preferable.
  • Preferred examples of C 1 -C 6 alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl or hexyl.
  • HNR 2 R 3 examples include dimethylamine, diethylamine, dipropylamine, diisopropylamine, dibutylamine, disec-butylamine, diisobutylamine, ditert-butylamine, dipentylamine or dihexylamine. It is not limited.
  • the amount of HNR 2 R 3 used is not particularly limited as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., usually 0.8 to 3.0 mol, preferably 0.9 to 2.0 mol, relative to 1 mol of the raw material of formula (I), A range of 0.9 to 1.5 mol can be exemplified.
  • bases examples include alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, alkali metal hydrogen carbonates, alkaline earth metal hydrogen carbonates Inorganic bases such as pyridines, quinolines, isoquinolines, tertiary amines, secondary amines, primary amines, aromatic amines, cyclic amines, alkali metal carboxylates, alkaline earth carboxylates Although organic bases, such as a metal salt, are mentioned, It is not limited to these.
  • examples of the base used preferably include alkali metal hydroxides, alkali metal carbonates, alkali metal hydrogen carbonates, tertiary amines, carvone
  • An acid alkali metal salt more preferably an alkali metal hydroxide, an alkali metal carbonate, an alkali metal hydrogencarbonate, and still more preferably an alkali metal hydroxide.
  • Preferable examples of the base to be used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, sodium acetate, potassium acetate, more preferably sodium hydroxide, water
  • Examples include potassium oxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate and the like.
  • the form of the base used is not particularly limited as long as the reaction proceeds.
  • Examples of the form of the base to be used include a solid or liquid containing only a base, an aqueous solution having an arbitrary concentration, or a solution of a solvent other than water.
  • the base to be used may be used alone or in combination of two or more in any desired ratio.
  • Solvent systems that can be used include, for example, aromatic hydrocarbon derivatives, aliphatic hydrocarbons, halogenated aliphatic hydrocarbons, ethers, alcohols, nitriles, amides, alkylureas, sulfoxides. , Sulfones, ketones, carboxylic esters, carboxylic acids, aromatic heterocycles, water, and combinations of two or more of these in any proportion.
  • examples of the solvent system to be used are preferably aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, ethers, alcohols, nitriles.
  • solvent system examples include toluene, xylene, chlorobenzene, dichlorobenzene, nitrobenzene, dichloromethane, tetrahydrofuran (THF), diisopropyl ether, dibutyl ether, cyclopentyl methyl ether (CPME), methyl-tert-butyl ether, methanol, Ethanol, propanol, 2-propanol, butanol, acetonitrile, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), N, N′-dimethylimidazolidinone ( DMI), dimethyl sulfoxide (DMSO), sulfolane, water, and solvent systems comprising them, more preferably toluene, xylene, chlorobenzene, dichlorobenzene, nitro , Dichloromethane, tetrahydrofur
  • the amount of the solvent used to form the solvent system is not particularly limited as long as the reaction system can be sufficiently stirred.
  • the amount of water is usually 0 (zero) to 10.0 L (liter), preferably 0.01, relative to 1 mol of the raw material of formula (I).
  • a range of ⁇ 10.0 L, more preferably 0.1-5.0 L, and still more preferably 0.2-3.0 L can be exemplified.
  • the amount of the above-mentioned solvent other than water is usually 0 (zero) to 10.0 L (liter), preferably 0.01 to 10 with respect to 1 mol of the raw material of formula (1).
  • a range of 0.0 L, more preferably 0.1 to 5.0 L, and still more preferably 0.2 to 3.0 L can be exemplified.
  • the mixing ratio of water and a solvent other than water is not particularly limited as long as the reaction proceeds. When two or more solvents other than water are used, the mixing ratio of the solvents is not particularly limited as long as the reaction proceeds.
  • reaction temperature is not particularly limited. From the viewpoint of yield, by-product suppression and economic efficiency, it is usually in the range of 10 ° C to 100 ° C, preferably 40 ° C to 95 ° C, more preferably 45 ° C to 85 ° C, more preferably 50 ° C to 70 ° C. Can be illustrated.
  • reaction time is not particularly limited. From the viewpoint of yield, by-product suppression, economic efficiency, etc., the range of usually 0.5 hours to 48 hours, preferably 0.5 hours to 24 hours, more preferably 1 hour to 12 hours may be exemplified. it can.

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

Abstract

La présente invention concerne un nouveau dérivé de cyclopenténone industriellement recherché et son procédé de production. Des applications pratiques et industrielles de ce qui suit sont prévues : les nouveaux composés (formules (I) et (II)) et les procédés de production de ceux-ci selon la présente invention, un nouvel intermédiaire industriellement recherché pour un dérivé de prostaglandine et similaire, et un procédé de production de celui-ci.
PCT/JP2016/087257 2016-12-14 2016-12-14 Dérivé de cyclopenténone et son procédé de production Ceased WO2018109872A1 (fr)

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JPH0358960A (ja) * 1989-07-28 1991-03-14 Bayer Ag Ｎ―アルキル化アニリンの製造方法
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