Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
  • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
  • C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
  • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
  • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
  • C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
  • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
  • C07D471/04—Ortho-condensed systems
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
  • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
  • C07D491/04—Ortho-condensed systems
  • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
  • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
  • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
  • C07D491/04—Ortho-condensed systems
  • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

Definitions

• the present invention relates to a method for producing an N-substituted lactam compound.
• R 1 has an aralkyl group which may have a substituent, an alkenyl group which may have a substituent, an alkynyl group which may have a substituent, and a substituent. represents also heterocyclic group optionally having an aromatic hydrocarbon group or a substituted group, R a represents a methylene group which may have a substituent, R b is substituted Represents a divalent alicyclic hydrocarbon group which may be substituted or a divalent heterocyclic group which may have a substituent; R c represents a methylene group which may have a substituent; Or 2 and n represents 0, 1, 2 or 3.
• the present invention relates to formula (1) [Wherein, R a represents a methylene group which may have a substituent, and R b has a divalent alicyclic hydrocarbon group or a substituent which may have a substituent. represents may also be a divalent heterocyclic group, R c represents a methylene group which may have a substituent, m represents 1 or 2, n represents 0, 1, 2 or 3. ]
• a compound represented by formula (3) having a step of reacting with an amine compound (amine compound (2)) in the presence of water.
• R 1 , R a , R b , R c , m and n are as defined above.
• the manufacturing method of the N-substituted lactam compound (N-substituted lactam compound (3)) shown by these is provided.
• Examples of the divalent alicyclic hydrocarbon group represented by R b include a cycloalkanediyl group, a cycloalkenediyl group, and a cycloalkynediyl group.
• cycloalkanediyl group examples include a cyclopropanediyl group (cyclopropane-1,1-diyl group, cyclopropane-1,2-diyl group), a cyclobutanediyl group (cyclobutane-1,1-diyl group, cyclobutane- 1,2-diyl group, etc.), cyclopentanediyl group (cyclopentane-1,1-diyl group, cyclopentane-1,2-diyl group, etc.), cyclohexanediyl group (cyclohexane-1,1-diyl group, cyclohexane) -1,2-diyl group, etc.), cycloheptanediyl group (cycloheptane-1,1-diyl group, cycloheptane-1,2-diyl group, etc.), cyclooct
• cycloalkenediyl group examples include a cyclobutenediyl group (2-cyclobutene-1,1-diyl group, 1-cyclobutene-1,2-diyl group, 2-cyclobutene-1,2-diyl group, etc.), cyclopentene, and the like.
• Diyl group (2-cyclopentene-1,1-diyl group, 1-cyclopentene-1,2-diyl group, etc.), cyclohexene diyl group (2-cyclohexene-1,1-diyl group, 1-cyclohexene-1,2- Diyl group, etc.), cycloheptene diyl group (2-cycloheptene-1,1-diyl group, 1-cycloheptene-1,2-diyl group, etc.), cyclooctene diyl group (2-cyclooctene-1,1-diyl) Group, 1-cyclooctene-1,2-diyl group, etc.), cyclononenediyl group (2-cyclononene-1,1-diyl group, 1-cyclononene- And 2-diyl group), a cycloalkyl decene-diyl (2-cyclodecene-1,1-diyl group,
• Examples of the cycloalkynediyl group include a cyclooctynediyl group (2-cyclooctyne-1,1-diyl group, 3-cycloheptin-1,2-diyl group, etc.), a cyclononinediyl group (2-cyclononine-1). , 1-diyl group, 3-cyclononine-1,2-diyl group, etc.), cyclodecine diyl group (2-cyclodecyne-1,1-diyl group, 3-cyclodecyne-1,2-diyl group, etc.), etc. C 8 -C 10 cycloalkynediyl is mentioned.
• Examples of the divalent heterocyclic group represented by R b include a monocyclic or bicyclic aromatic or non-aromatic group containing 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom.
• the bivalent heterocyclic group of these is mentioned. Specific examples include pyrrole diyl group, thiophene diyl group, frangiyl group, pyrazole diyl group, imidazole diyl group, oxazole diyl group, isoxazole diyl group, oxadiazole diyl group, triazole diyl group, thiadiazole diyl group, isothiazole.
• 5-membered aromatic heterocyclic group such as diyl group; 6-membered aromatic heterocyclic ring such as pyridinediyl group, pyridazinediyl group, pyrimidinediyl group, pyrazinediyl group; pyrrolidinediyl group, pyrrolinediyl group, imidazolinediyl group, pyrazolidine 5-membered non-aromatic heterocyclic group such as diyl group, pyrazolinediyl group, oxazolidinediyl group, thiazolidinediyl group; pyrandiyl group, piperidinediyl group, tetrahydropyridinediyl group, dihydropyridinediyl group, piperazinediyl group, morpholine 6-membered non-aromatic heterocyclic group such as yl group and thiomorpholine diyl group; indole diyl group, isoind
• Examples of the aralkyl group represented by R 1 include a C 7 to C 12 aralkyl group, and specific examples thereof include a benzyl group, a phenylethyl group, and naphthylmethyl.
• Examples of the alkenyl group represented by R 1 include a C 2 to C 10 alkenyl group. Specifically, a vinyl group, an allyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group, an octenyl group, Nonenyl group, decenyl group, etc. are mentioned.
• Examples of the alkynyl group represented by R 1 include a C 2 to C 10 alkynyl group, specifically, an ethynyl group, a propargyl group, a butynyl group, a pentynyl group, a hexynyl group, a heptynyl group, an octynyl group, Noninyl group, decynyl group, etc. are mentioned.
• Examples of the aromatic hydrocarbon group represented by R 1 include a C 6 to C 10 aryl group, and specific examples thereof include a phenyl group and a naphthyl group.
• heterocyclic group represented by R 1 examples include, for example, a monocyclic or bicyclic aromatic group containing 1 to 3 heteroatoms independently selected from a nitrogen atom, an oxygen atom, and a sulfur atom, or a non-cyclic group.
• Aromatic heterocyclic groups and the like can be mentioned. Specific examples include 5-membered aromatic complex such as pyrrolyl, thienyl, furyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, etc.
• Ring group 6-membered aromatic heterocycle such as pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group; pyrrolidinyl group, pyrrolinyl group, imidazolidinyl group, imidazolinyl group, pyrazolidinyl group, pyrazolinyl group, oxazolidinyl group, thiazolidinyl group, isothiazolyl group, etc.
• 6-membered aromatic heterocycle such as pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group; pyrrolidinyl group, pyrrolinyl group, imidazolidinyl group, imidazolinyl group, pyrazolidinyl group, pyrazolinyl group, oxazolidinyl group, thiazolidinyl group, isothiazolyl group, etc.
• 5-membered non-aromatic heterocyclic group 6-membered non-aromatic heterocyclic group such as pyranyl group, piperidyl group, tetrahydropyridyl group, dihydropyridyl group, piperazinyl group, morpholinyl group, thiomorpholinyl group; indolyl group, isoin Bicyclic aromatic heterocycles such as ryl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, isobenzofuranyl, indazolyl, benzimidazolyl, imidazolpyridyl, benzothiazolyl, quinolyl, and isoquinolyl A group; bicyclic non-aromatic heterocyclic groups such as indolinyl group, isoindolinyl group, thiochromanyl group, chromanyl group and the like.
• Examples of the substituent that the methylene group, divalent alicyclic hydrocarbon group, divalent heterocyclic group, aralkyl group, aromatic hydrocarbon group and heterocyclic group may have include a halogen atom (fluorine Atom, chlorine atom, bromine atom, iodine atom), alkoxy group, cycloalkoxy group, nitro group, cyano group, alkyl group, cycloalkyl group, aryl group (the aryl group has an alkyl group, halogen atom, nitro) Or may be substituted one or more.
• halogen atom fluorine Atom, chlorine atom, bromine atom, iodine atom
• alkoxy group alkoxy group
• cycloalkoxy group nitro group
• cyano group alkyl group
• aryl group the aryl group has an alkyl group, halogen atom, nitro
• Or may be substituted one or more.
• alkenyl group and alkynyl group may have include, for example, a halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), alkoxy group, nitro group, cyano group, aryl group
• the aryl group may have an alkyl group, a halogen atom, or nitro), and may be substituted by one or more.
• alkoxy group include linear or branched C 1 -C 10 alkoxy groups, and specifically include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, and sec-butoxy.
• cycloalkoxy group examples include a C 4 to C 10 cycloalkoxy group, and specifically include a cyclobutyloxy group, a cyclopentyloxy group, a cyclohexyloxy group, a cycloheptyloxy group, a cyclooctyloxy group, and a cyclononyloxy group.
• alkyl group examples include linear or branched C 1 -C 10 alkyl groups, and specifically include methyl group, ethyl group, propyl group, isopropyl group, butyl group, sec-butyl group, tert- Examples thereof include a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group.
• a methyl group, an ethyl group, an isopropyl group, a sec-butyl group, a tert-butyl group, etc. are mentioned.
• Examples of the cycloalkyl group include a C 4 to C 10 cycloalkyl group, and specific examples include a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a cyclononyl group, and a cyclodecyl group.
• Examples of the aryl group include a C 6 to C 10 aryl group, and specific examples include a phenyl group and a naphthyl group.
• R 1 is preferably an aralkyl group which may have a substituent or an alkenyl group which may have a substituent, more preferably a benzyl group or a substituent which may have a substituent.
• R a is preferably a methylene group.
• m is preferably 1.
• R b is preferably a divalent cycloalkanediyl group which may have a substituent or a monocyclic divalent heterocyclic group which may have a substituent, and more preferably, A divalent cycloalkanediyl group which may have a substituent, particularly preferably a divalent C 3 to C 6 cycloalkanediyl group which may have a substituent.
• R c is preferably a methylene group.
• n is preferably 0 or 1, more preferably 0.
• Examples of the lactone compound (1) include ⁇ -lactone compounds, ⁇ -lactone compounds, and ⁇ -lactone compounds, and preferably ⁇ -lactone compounds.
• lactone compound (1) examples include compounds represented by the following formulas (1-1) to (1-12).
• the lactone compound (1) may be an optically active substance.
• a particularly preferred lactone compound (1) is a lactone compound (1) in which R a is a methylene group, R b is a divalent cycloalkanediyl group which may have a substituent, m is 1 and n is 0. is there.
• the lactone compound (1) represented by the following formula (1 ′) is preferable.
• R d represents an alkanediyl group having 1 to 4 carbon atoms which may have a substituent.
• the lactone compound (1) represented by the formula (1 ′) is represented by the formulas (1-1) to (1-6) and (1-9). ) Are applicable.
• Examples of the amine compound (2) include allylamine, aniline, chloroaniline, dichloroaniline, trichloroaniline, fluoroaniline, methoxyaniline, dimethoxyaniline, nitroaniline, dinitroaniline, aminofuran, aminopyrrole, aminothiophene, aminopyran, amino Pyridine, benzylamine, chlorobenzylamine, dichlorobenzylamine, trichlorobenzylamine, fluorobenzylamine, methoxybenzylamine, dimethoxybenzylamine, nitrobenzylamine, dinitrobenzylamine, chlorobenzylamine, dichlorobenzylamine, trichlorobenzylamine, fluoro Benzylamine, methylbenzylamine, ethylbenzylamine, methoxybenzylamine, dimethoxybenzene Jiruamin, aminomethyl benzonitrile, phenylethyl amine and naphthyl
• N-substituted lactam compound (3) examples include compounds represented by the following formulas (3-1) to (3-48).
• the N-substituted lactam compound (3) may be an optically active substance.
• the N-substituted lactam compound (3) is produced by a step of reacting the lactone compound (1) and the amine compound (2) in the presence of water.
• the lactone compound (1) is a commercially available compound or can be easily prepared from a commercially available compound. For example, it can be prepared according to US2009 / 163722.
• the amount of the amine compound (2) to be used is 0.8 to 10 mol, preferably 1 to 6 mol, more preferably 1.1 to 4 mol, and still more preferably 1. mol per 1 mol of the lactone compound (1). It is in the range of 7 to 3 mol.
• the amount of water used in this step is preferably in the range of 3 to 500 mol, more preferably 4 to 210 mol, per 1 mol of the lactone compound (1).
• This step is a reaction in the presence of water and is usually a reaction using water as a solvent, but it can also be performed in a mixed solvent of water and an organic solvent.
• organic solvent examples include aliphatic hydrocarbons (hexane, heptane, cyclohexane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, ethylbenzene, chlorobenzene, dichlorobenzene, etc.), halogenated hydrocarbons (dichloromethane, dichloroethane, Chloroform, chlorobutane, etc.), ether (tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether, methyl tert-butyl ether, diethyl ether, etc.), alcohol (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-methyl- 2-propanol, etc.), nitriles (acetonitrile, propionitrile, etc.), and mixtures of two or more thereof.
• aliphatic hydrocarbons hexane,
• Preferred organic solvents include methanol and ethanol.
• the amount of the organic solvent used is, for example, in the range of 0 to 100 parts by weight, preferably 0.1 to 20 parts by weight, more preferably 0.1 to 2 parts by weight with respect to 1 part by weight of the lactone compound (1). is there.
• an additive examples include inorganic acids (hydrogen chloride, hydrogen bromide, hydrofluoric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid, etc.), organic acids (formic acid, acetic acid, citric acid, oxalic acid, methanesulfone).
• the reaction temperature is, for example, in the range of 100 to 300 ° C, preferably 130 to 210 ° C, more preferably 160 to 210 ° C.
• This step is also preferably performed under pressurized conditions.
• the pressure under the pressurizing condition is, for example, in the range of 0.1 to 5 MPa, preferably 0.5 to 2 MPa.
• the N-substituted lactam compound (3) can be isolated by subjecting the mixture obtained by the reaction to post-treatment.
• the mixture is further mixed with water and an organic solvent that can be separated to separate the liquid, so that excess amine compound (2), additive, and these are hydrolyzed.
• the decomposed component can be distributed to the aqueous layer, while the N-substituted lactam compound (3) can be distributed to the organic layer.
• the acid layer is acidified by adding an acid, or the aqueous layer at the time of the liquid separation operation is acidified by mixing an acidic aqueous solution with the reaction mixture.
• An amount of the amine compound (2) can be efficiently distributed to the aqueous layer.
• a preferable range of the pH of the aqueous layer is 1 to 7, and a more preferable range is 4 to 6.
• organic solvents that can be separated from water include aliphatic hydrocarbons (hexane, heptane, cyclohexane, etc.), aromatic hydrocarbons (benzene, toluene, xylene, ethylbenzene, chlorobenzene, dichlorobenzene, etc.), and halogenated hydrocarbons.
• the organic layer obtained by liquid separation may be further subjected to water washing, inorganic salt water washing, basic water washing, acid water washing, or the like. Water washing, inorganic salt washing, basic water washing, acidic water washing, etc. may be repeated.
• the solution containing the N-substituted lactam compound (3) thus obtained may be used as it is as a chemical raw material, a pharmaceutical intermediate for producing agricultural chemicals, or the like, or by N-substituted lactam compound (3) by solvent concentration or the like.
• the isolated N-substituted lactam compound (3) may be used as a chemical raw material, an intermediate for the production of medical and agrochemicals, and the like.
• the N-substituted lactam compound (3) may be further purified by methods such as column chromatography and recrystallization.
• Example 1 Synthesis of (1R, 5S) -3-benzyl-6,6-dimethyl-3-azabicyclo [3.1.0] hexan-2-one (Compound A) (1R, 5S) -6 in a 200 mL autoclave , 6-dimethyl-3-oxabicyclo [3.1.0] hexane-2-one (Compound B) 19.3g (118.6mmol) in toluene solution 19.3g and benzylamine 25.7g (239.7mmol) ) And 64.8 g (3.6 mol) of water were added and mixed, and then heated to 180 ° C. under a pressure of 0.9 MPa.
• Example 3 Synthesis of Compound A A 1000 mL autoclave was charged with 64.77 g of a toluene solution containing 50.0 g (396.3 mmol) of Compound B, 84.9 g (792.7 mmol) of benzylamine, and 214 g (11.9 mol) of water and mixed. Then, it was heated to 195 ° C. under a pressure of 1.6 MPa.
• Example 11 Synthesis of Compound A 14.71 g of a toluene solution containing 11.36 g (90.1 mmol) of Compound B in a 200 mL autoclave, 19.3 g (180 mmol) of benzylamine, 16.2 g (899 mmol) of water, and 22.7 g of methanol After charging and mixing, the mixture was heated to 160 ° C. under a pressure of 1.0 MPa. The mixture was stirred at the same temperature for 21 hours to obtain a reaction mixture containing 17.5 g (81.3 mmol, 90.3% yield) of Compound A. The yield was determined by analyzing the reaction mixture under the same HPLC conditions as in Example 1.
• Example 12 Synthesis of Compound A 9.81 g of a toluene solution containing 7.57 g (60.0 mmol) of Compound B in a 200 mL autoclave, 12.85 g (120 mmol) of benzylamine, 10.84 g (600 mmol) of water, and 15.1 g of methanol. After charging and mixing, the mixture was heated to 170 ° C. under a pressure of 1.2 MPa. The mixture was stirred at the same temperature for 15 hours to obtain a reaction mixture containing 12.1 g (56.2 mmol, yield 93.5%) of compound A. The yield was determined by analyzing the reaction mixture under the same HPLC conditions as in Example 1.
• Example 13 Synthesis of Compound A
• Compound B In a 200 mL autoclave, 5.05 g (39.6 mmol, content 99.0%) of Compound B, 8.49 g (79.3 mmol) of benzylamine, 17.96 g (997 mmol) of water, and 10.03 g of methanol were added. After charging and mixing, the mixture was heated to 165 ° C. under a pressure of 0.9 MPa. The mixture was stirred at the same temperature for 12 hours to obtain a reaction mixture containing 8.39 g (39.0 mmol, yield 98.5%) of Compound A. Thereafter, 3.99 g of 35% hydrochloric acid was added to adjust the pH to 5, followed by extraction twice with 15 g of toluene.
• Example 14 Synthesis of Compound A 14.69 g of toluene solution containing 11.34 g (90.0 mmol) of Compound B in a 200 mL autoclave, 16.39 g (153 mmol) of benzylamine, 16.2 g (900 mmol) of water and 22.78 g of methanol After charging and mixing, the mixture was heated to 170 ° C. under a pressure of 1.2 MPa. The mixture was stirred at the same temperature for 15 hours to obtain a reaction mixture containing 17.96 g (83.4 mmol, yield 92.8%) of Compound B. The yield was determined by analyzing the reaction mixture under the same HPLC conditions as in Example 1.
• Example 15 Synthesis of Compound A After charging and mixing 9.80 g of a toluene solution containing 7.57 g (60.0 mmol) of Compound B, 32.1 g (300 mmol) of benzylamine and 10.8 g (600 mol) of water in a 200 mL autoclave. And heated to 170 ° C. under a pressure of 0.6 MPa. The mixture was stirred at the same temperature for 15 hours to obtain a reaction mixture containing 11.8 g (54.9 mmol, yield 91.5%) of compound A. The yield was determined by analyzing the reaction mixture under the same HPLC conditions as in Example 1.
• Example 16 Synthesis of Compound A 14.69 g of a toluene solution containing 11.34 g (89.9 mmol) of Compound B in a 200 ml autoclave, 19.26 g (179.8 mmol) of benzylamine, 16.25 g (899 mmol) of water, and methanol 22. 71 g and p-toluenesulfonic acid monohydrate 3.51 g (18.0 mmol) were charged and mixed, and then heated to 170 ° C. under a pressure of 1.2 MPa. The mixture was stirred at the same temperature for 15 hours, and the obtained reaction mixture was quantitatively analyzed under the same HPLC conditions as in Example 1. The yield of compound A based on compound B was 95.4%.
• Example 17 Synthesis of Compound A 4.90 g of a toluene solution containing 3.78 g (30.0 mmol) of Compound B in a 100 ml autoclave, 3.54 g (33.0 mmol) of benzylamine, 5.5 g (305 mmol) of water, and ⁇ -alumina 0.38 g (3.00 mmol) was charged, mixed and heated to 170 ° C. in an autoclave. The mixture was stirred at the same temperature for 15 hours, and water was added to the resulting reaction mixture. After stirring, the mixture was separated, and the organic layer and the aqueous layer were quantitatively analyzed under the same HPLC conditions as in Example 1. The yield of compound A based on compound B was 89.9%.
• Example 18 Synthesis of Compound A
• a 1000 mL autoclave was charged with 64.77 g of a toluene solution containing 50.0 g (396.3 mmol) of Compound B, 84.9 g (792.7 mmol) of benzylamine and 214 g (11.9 mol) of water and mixed. Then, it was heated to 210 ° C. under a pressure of 2.0 MPa. The mixture was stirred at the same temperature for 10 hours to obtain a reaction mixture containing 81.90 g (380.4 mmol, yield 96.0%) of Compound A. The yield was determined by analyzing under the same HPLC conditions as in Example 1.
• Example 19 Synthesis of (1R, 5S) -3-allyl-6,6-dimethyl-3-azabicyclo [3.1.0] hexane-2-one
• Compound B 5.0 g (39.6 mmol) and allylamine in a 100 ml autoclave 4.53 g (79.3 mmol) and 21.4 g (1.19 mol) of water were charged and mixed, and then heated to 175 ° C. under pressure. The mixture was stirred at the same temperature for 15 hours, and the obtained reaction mixture was quantitatively analyzed under the same HPLC conditions as in Example 1. The yield based on compound B was 100%.
• an N-substituted lactam compound of the formula (1) useful as a chemical raw material, a production intermediate for medical and agricultural chemicals, and the like can be produced in high yield.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Plural Heterocyclic Compounds (AREA)
• Other In-Based Heterocyclic Compounds (AREA)
• Hydrogenated Pyridines (AREA)
• Pyrrole Compounds (AREA)

Priority Applications (1)

Applications Claiming Priority (4)

Publications (1)

Family

ID=47259457

Family Applications (1)

Country Status (3)

Cited By (8)

Families Citing this family (1)

Citations (2)

Family Cites Families (5)

• 2011
  • 2011-12-14 JP JP2011273364A patent/JP2013010734A/ja active Pending
• 2012
  • 2012-05-25 CN CN201280024610.4A patent/CN103547569A/zh active Pending
  • 2012-05-25 WO PCT/JP2012/064247 patent/WO2012165606A1/ja active Application Filing

Patent Citations (2)

Non-Patent Citations (2)

Also Published As

Similar Documents

Legal Events