CN111116604B - Process method for preparing fluorescamine - Google Patents
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- CN111116604B CN111116604B CN201911345193.3A CN201911345193A CN111116604B CN 111116604 B CN111116604 B CN 111116604B CN 201911345193 A CN201911345193 A CN 201911345193A CN 111116604 B CN111116604 B CN 111116604B
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- 238000000034 method Methods 0.000 title claims abstract description 31
- ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 239000007800 oxidant agent Substances 0.000 claims abstract description 13
- 229940100595 phenylacetaldehyde Drugs 0.000 claims abstract description 11
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000001590 oxidative effect Effects 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 230000003647 oxidation Effects 0.000 claims abstract description 7
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 7
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 6
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 4
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 239000012286 potassium permanganate Substances 0.000 claims description 3
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 3
- 239000000047 product Substances 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 3
- NIQCNGHVCWTJSM-UHFFFAOYSA-N Dimethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(=O)OC NIQCNGHVCWTJSM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- FBSAITBEAPNWJG-UHFFFAOYSA-N dimethyl phthalate Natural products CC(=O)OC1=CC=CC=C1OC(C)=O FBSAITBEAPNWJG-UHFFFAOYSA-N 0.000 description 1
- 229960001826 dimethylphthalate Drugs 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- MGNPLIACIXIYJE-UHFFFAOYSA-N n-fluoroaniline Chemical compound FNC1=CC=CC=C1 MGNPLIACIXIYJE-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- -1 primary amine compound Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a process method for preparing fluorescamine, which comprises the following steps: the method comprises the following steps: ninhydrin is used as a raw material and reacts with phenylacetaldehyde under the catalysis of a proper amount of catalyst to obtain a tricyclic intermediate; step two: the tricyclic intermediate is used as a raw material and reacts under the oxidation of a proper amount of an oxidant to obtain the fluorescamine. The method has the advantages of short synthetic route, simple process, mild reaction conditions and high reaction yield.
Description
Technical Field
The invention relates to the field of biochemical reagents, in particular to a process method for preparing fluorescamine.
Background
Fluorescamine is a non-planar spiro compound that does not fluoresce itself, but can form stable, highly fluorescent compounds upon reaction with primary amines. Due to its property of fluorescence spike after reaction with primary amines, it is used to characterise compounds containing primary amine groups. Is widely applied to the fluorescence measurement of amino acid, protein and proteolytic enzyme at present.
The fluorescence amine has the obvious advantages of low background, high sensitivity and the like for detecting the primary amine compound, and the detection sensitivity can reach 10-12 mol.
Fluoroaniline has only 1 synthetic route reported so far, namely the following route reported in 1976 by Journal of Organic Chemistry,41(2),388-9, 1976:
the method adopts a 7-step synthesis method, and dimethyl phthalate diethyl ester is taken as a starting material, condensed with ethyl acetate, de-esterified with hydrochloric acid, condensed with benzaldehyde, epoxidized with hydrogen peroxide, subjected to ring opening with sodium hydroxide, condensed with N, N-dimethylformamide dimethyl acetal, and subjected to ring closing to obtain the fluorescamine.
This method has two more serious problems: firstly, the reaction route is long, 7 steps of reaction are required, the ring needs to be closed continuously in the whole process, the ring is opened and then closed, and the synthesis operation is very complicated; secondly, the reaction conditions are harsh, the first step, the sixth step and the seventh step need to be carried out under anhydrous conditions, the overall yield is also low, and the overall yield of the reaction in the 7 steps is lower than 10%, so that the product synthesis cost is high. These two problems make it very difficult to scale up the product to the kilogram level and ten kilograms.
In order to solve the problems of long synthetic steps, harsh reaction conditions and complex operation of the existing process route of the fluorescamine, the method for searching the fluorescamine, which has reasonable route design, mild reaction conditions, safety and reliability, has very important significance.
Disclosure of Invention
In order to overcome the defects in the prior art, the embodiment of the invention provides a process method for preparing fluorescamine, which has the advantages of short synthetic route, simple process, mild reaction conditions and high reaction yield.
In order to achieve the above purpose, the embodiment of the present application discloses a process for preparing fluorescamine, which comprises the following steps:
the method comprises the following steps: ninhydrin is used as a raw material and reacts with phenylacetaldehyde under the catalysis of a proper amount of catalyst to obtain a tricyclic intermediate;
step two: the tricyclic intermediate is used as a raw material and reacts under the oxidation of a proper amount of an oxidant to obtain the fluorescamine.
Preferably, the catalyst is acetic acid.
Preferably, the reaction of the ninhydrin with the phenylacetaldehyde is carried out in a solvent under catalysis of a proper amount of catalyst, and the solvent is one or more of the following substances: tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, DMF, DMSO.
Preferably, the dosage of the phenylacetaldehyde is as follows: 0.5 to 3.5 equivalents; the dosage of the catalyst is as follows: 0.01 to 50 equivalents; the reaction temperature in the first step is 50-200 ℃.
Preferably, the oxidant is one or more of the following: sodium periodate, sodium tungstate and potassium permanganate.
Preferably, the reaction of the tricyclic intermediate under oxidation with a suitable amount of an oxidizing agent is carried out in a solvent, wherein the solvent used is one or more of the following: water, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, ethanol, methanol, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, DMF, DMSO.
Preferably, the amount of the oxidant is: 0.1 to 3.5 equivalents; the reaction temperature in the second step is-20-200 ℃.
The invention has the following beneficial effects:
1. the synthetic route is short, only 2 steps of reaction are needed, and the process is simplified;
2. the process is simple, the reaction condition is mild, and extreme reaction conditions are not needed;
3. the reaction yield is high, the product purity is high, the production cost is greatly reduced, and the requirement of large-scale industrial production of the product can be fully met.
In order to make the aforementioned and other objects, features and advantages of the invention more comprehensible, preferred embodiments accompanied with figures are described in detail below.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 shows the nuclear magnetic spectrum of example 1 of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the description of the present invention, it should be noted that the terms "upper", "lower", "bottom", "inner", "outer", and the like indicate orientations or positional relationships based on those shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the referred device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first", "second", etc. are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first," "second," etc. may explicitly or implicitly include one or more of that feature.
In order to achieve the above object, the present invention provides a process for preparing fluorescamine, comprising the following steps:
the method comprises the following steps: ninhydrin is used as a raw material and reacts with phenylacetaldehyde under the catalysis of a proper amount of catalyst to obtain a tricyclic intermediate;
step two: the tricyclic intermediate is used as a raw material and reacts under the oxidation of a proper amount of an oxidant to obtain the fluorescamine.
Preferably, the catalyst is acetic acid.
Preferably, the reaction of the ninhydrin with the phenylacetaldehyde is carried out in a solvent under catalysis of a proper amount of catalyst, and the solvent is one or more of the following substances: tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, DMF, DMSO.
Preferably, the dosage of the phenylacetaldehyde is as follows: 0.8 to 1.2 equivalents; the dosage of the catalyst is as follows: 0.1 to 5 equivalents; the reaction temperature in the first step is 50-100 ℃.
Preferably, the oxidant is one or more of the following: sodium periodate, sodium tungstate and potassium permanganate.
Preferably, the reaction of the tricyclic intermediate under oxidation with a suitable amount of an oxidizing agent is carried out in a solvent, wherein the solvent used is one or more of the following: water, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, ethanol, methanol, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, DMF, DMSO.
Preferably, the amount of the oxidant is: 0.5 to 1.5 equivalents; the reaction temperature of the second step is 20-100 ℃.
Example 1
The method comprises the following steps: preparation of tricyclic intermediates
Under stirring at room temperature, 3.2Kg of ninhydrin, 2.4Kg of phenylacetaldehyde, 2Kg of acetic acid, and 10L of tetrahydrofuran were sequentially added to a 20L glass reaction vessel, and stirred to obtain a reaction solution.
Further, the reaction solution was heated to 70 ℃ and stirred to react for 6 hours, and the reaction was completed.
Further, the reaction solution was distilled under reduced pressure to recover the solvent and the catalyst, the residue was washed with water by beating, recrystallized with ethyl acetate, and finally dried in oven vacuum to obtain 5.3Kg of a yellow solid (tricyclic intermediate) with a yield of 94%.
Step two: preparation of fluorescamine
And under the stirring at room temperature, 5.3Kg of the tricyclic intermediate obtained in the previous step, 4.1Kg of sodium periodate and 20Kg of water are sequentially added into a 50L glass reaction kettle, and the mixture is stirred uniformly to obtain a reaction solution.
Further, the reaction solution was stirred at room temperature for 8 hours to complete the reaction.
Further, the reaction solution is decompressed and filtered, a filter cake is washed by 2Kg of water and then recrystallized by tert-butyl methyl ether, and finally dried in an oven in vacuum to obtain 5.1Kg of yellow solid powdery product with the yield of 96%.
HPLC purity of the product: 99.1 percent.
Melting point of the product: 157 to 158 ℃.
Referring to FIG. 1, the nuclear magnetic data for example 1 is as follows: 1H NMR (400MHz, DMSO-d 6): δ 8.76(s, 1H), 8.03(d, 1H), 7.75(m, 4H), 7.42(m, 4H).
The synthesis route adopted by the embodiment is short, only 2 steps of reaction are needed, and the process is simplified; the process is simple, the reaction condition is mild, and extreme reaction conditions are not needed; the reaction yield is high, the product purity is high, the production cost is greatly reduced, and the requirement of large-scale industrial production of the product can be fully met.
The synthesis route adopted by the embodiment is short, only 2 steps of reaction are needed, and the process is simplified; the process is simple, the reaction condition is mild, and extreme reaction conditions are not needed; the reaction yield is high, the product purity is high, the production cost is greatly reduced, and the requirement of large-scale industrial production of the product can be fully met.
The principle and the implementation mode of the invention are explained by applying specific embodiments in the invention, and the description of the embodiments is only used for helping to understand the method and the core idea of the invention; meanwhile, for a person skilled in the art, according to the idea of the present invention, there may be variations in the specific embodiments and the application scope, and in summary, the content of the present specification should not be construed as a limitation to the present invention.
Claims (7)
1. A process for preparing fluorescamine, comprising the steps of:
the method comprises the following steps: ninhydrin is used as a raw material and reacts with phenylacetaldehyde under the catalysis of a proper amount of catalyst to obtain a tricyclic intermediate;
step two: reacting the tricyclic intermediate serving as a raw material under the oxidation of a proper amount of oxidant to obtain the fluorescamine
2. The process of claim 1, wherein said catalyst is acetic acid.
3. The process for preparing fluorescamine according to claim 1, wherein the reaction of ninhydrin with phenylacetaldehyde is carried out in a solvent catalyzed by a suitable amount of catalyst, wherein the solvent is one or more of the following: tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, DMF, DMSO.
4. The process for preparing fluorescamine according to claim 1, wherein the phenylacetaldehyde is used in an amount of: 0.5 to 3.5 equivalents; the dosage of the catalyst is as follows: 0.01 to 50 equivalents; the reaction temperature in the first step is 50-100 ℃.
5. The process for preparing fluorescamine according to claim 1, wherein the oxidizing agent is one or more of the following: sodium periodate, sodium tungstate and potassium permanganate.
6. The process for preparing fluorescamine according to claim 1, wherein the reaction of the tricyclic intermediate under oxidation with a suitable amount of an oxidizing agent is carried out in a solvent, wherein the solvent used is one or more of the following: water, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, ethanol, methanol, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, DMF, DMSO.
7. The process for preparing fluorescamine according to claim 1, wherein the oxidizing agent is used in an amount of: 0.1 to 3.5 equivalents; the reaction temperature in the second step is-20-200 ℃.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000005201A1 (en) * | 1998-07-21 | 2000-02-03 | Novartis Ag | N-benzocycloalkyl-amide derivatives and their use as medicaments |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR101442015B1 (en) * | 2012-08-22 | 2014-09-25 | 한국화학연구원 | Spiro-benzofuanone derivatives, pharmaceutically acceptable salt thereof, preparation method thereof and pharmaceutical composition for treating influenza containing the same as an active ingredient |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000005201A1 (en) * | 1998-07-21 | 2000-02-03 | Novartis Ag | N-benzocycloalkyl-amide derivatives and their use as medicaments |
Non-Patent Citations (5)
| Title |
|---|
| A new, one-pot, efficient method for the synthesis of 5-methyl- 3H,30H-spiro[furan-2,10-isobenzofuran]-3,30-dione derivatives in water;Mohammad Reza Mohammadizadeh, 等;《Tetrahedron Letters》;20151130;第57卷(第3期);264-267 * |
| Facile Chemoselective synthesis of 2-(2-(Methoxycarbonyl)-3-oxo-2,3-dihydrobenzofuran-2-yl)benzoic acids and 3H,3H-Spiro[benzofuran-2,1-isobenzofuran]-3,3-dione derivatives;Neda Firoozi,等;《Applied Organometallic Chemistry》;20171231;第32卷;e3963 * |
| Mohammad Reza Mohammadizadeh, 等.A new, one-pot, efficient method for the synthesis of 5-methyl- 3H,30H-spiro[furan-2,10-isobenzofuran]-3,30-dione derivatives in water.《Tetrahedron Letters》.2015,第57卷(第3期),264-267. * |
| Unprecedented reaction of ninhydrin with ethyl cyanoacetate and diethyl malonate on ultrasonic irradiation;Yeshwinder Saini, 等;《Tetrahderon》;20151202;第72卷(第2期);257-263 * |
| Vasarene and vasarene-analogues: synthesis and characterization of self-assembled, voluminous ligands with specific affinity to M+F- ion-pairs;Ravell Bengiat,等;《Tetrahedron》;20160323;第72卷(第19期);2429-2439 * |
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