CN113527148A - Preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide - Google Patents
Preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide Download PDFInfo
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- CN113527148A CN113527148A CN202110579986.2A CN202110579986A CN113527148A CN 113527148 A CN113527148 A CN 113527148A CN 202110579986 A CN202110579986 A CN 202110579986A CN 113527148 A CN113527148 A CN 113527148A
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- phenoxyphenyl
- methanesulfonamide
- formamidoacetyl
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- BTXBRUSJXFSAJA-UHFFFAOYSA-N n-[2-[2-hydroxy-4-(methanesulfonamido)-5-phenoxyphenyl]-2-oxoethyl]formamide Chemical compound CS(=O)(=O)NC1=CC(O)=C(C(=O)CNC=O)C=C1OC1=CC=CC=C1 BTXBRUSJXFSAJA-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims abstract description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 17
- 230000008569 process Effects 0.000 claims abstract description 9
- 238000010520 demethylation reaction Methods 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 10
- OVFGHIVRJWQONU-UHFFFAOYSA-N n-[2-[4-(methanesulfonamido)-2-methoxy-5-phenoxyphenyl]-2-oxoethyl]formamide Chemical compound C1=C(C(=O)CNC=O)C(OC)=CC(NS(C)(=O)=O)=C1OC1=CC=CC=C1 OVFGHIVRJWQONU-UHFFFAOYSA-N 0.000 claims description 9
- 239000012452 mother liquor Substances 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 235000010265 sodium sulphite Nutrition 0.000 claims description 6
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 239000006227 byproduct Substances 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- KFZUDNZQQCWGKF-UHFFFAOYSA-M sodium;4-methylbenzenesulfinate Chemical compound [Na+].CC1=CC=C(S([O-])=O)C=C1 KFZUDNZQQCWGKF-UHFFFAOYSA-M 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000000967 suction filtration Methods 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 230000003472 neutralizing effect Effects 0.000 claims 1
- -1 N- [ 4-methyl (2-formamidoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide Chemical compound 0.000 abstract description 7
- 239000003814 drug Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 3
- ANMATWQYLIFGOK-UHFFFAOYSA-N Iguratimod Chemical compound CS(=O)(=O)NC1=CC=2OC=C(NC=O)C(=O)C=2C=C1OC1=CC=CC=C1 ANMATWQYLIFGOK-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229950003909 iguratimod Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- ILFDRUFFPZTDRV-UHFFFAOYSA-N C1=CC(=C(C=C1COCC2=CC(=C(C=C2)Cl)[N+](=O)[O-])[N+](=O)[O-])Cl Chemical compound C1=CC(=C(C=C1COCC2=CC(=C(C=C2)Cl)[N+](=O)[O-])[N+](=O)[O-])Cl ILFDRUFFPZTDRV-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- KVCGISUBCHHTDD-UHFFFAOYSA-M sodium;4-methylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1 KVCGISUBCHHTDD-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- OTVAEFIXJLOWRX-NXEZZACHSA-N thiamphenicol Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CO)NC(=O)C(Cl)Cl)C=C1 OTVAEFIXJLOWRX-NXEZZACHSA-N 0.000 description 1
- 229960003053 thiamphenicol Drugs 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide, which is characterized in that N- [ 4-methyl (2-formamidoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide is used as a raw material, NaBr is dissolved in N, N-Dimethylformamide (DMF) for demethylation reaction to prepare the N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide, and the preparation method of the N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide provided by the invention is environment-friendly and simple in process, high yield and low cost.
Description
Technical Field
The invention belongs to the technical field of medicines and chemical engineering, and relates to a novel preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide.
Background
Iguratimod (NSAIDs) is a non-retentive anti-inflammatory drug (NSAIDs) with the chemical name of 3-formamido-7-methanesulfonamido 6-phenoxy-4H-1-benzodipyran-4-one, is a novel disease relieving drug (DMARDs) developed and combined by Fushan and Wei medicinal companies and is used for treating Rheumatoid Arthritis (RA) and osteoarthritis (0A); compared with the prior DMARDs, the compound has quick response, equivalent curative effect to high-efficiency antirheumatic drugs (SAP and MTX), but low toxicity. The product can significantly reduce inflammatory reaction, selectively inhibit COX-2, and inhibit production of inflammatory cytokine, tumor necrosis factor, lymphocyte and immunoglobulin, and has effect of regulating autoimmunity; and the medicament has quick response, better curative effect and less adverse reaction compared with the prior medicament, and is also effective to patients with ineffective other medicaments.
N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide is a key intermediate in the synthesis process of Iguratimod.
The prior art takes 4-chloro-3-nitrobenzyl ether as a raw material, and prepares N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl by etherification, iron powder reduction, mesylation, acylation, Gattmann-Koch reaction, methoxy hydrolysis and other reactions]A methanesulfonamide. Wherein the methoxy group is hydrolyzed by reacting N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoloxyphenyl group]Methanesulphonamide in NaI/AlCl3/CH3Demethylation in CN system, yield is lower than 85%. The process uses expensive NaI, and produces CH3The I and the excessive NaI can not be recovered, so that the production cost is high and the environmental pollution is serious.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl]Process for the preparation of methanesulfonamides, starting from N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl]The methanesulfonamide is used as a raw material, and NaBr/N, N-Dimethylformamide (DMF) is used for demethylation reaction, so that methyl on a 5-position is selectively removed, and the yield of a final product is over 90 percent; the invention adopts cheap NaBr to replace NaI to carry out demethylation reaction, thus greatly reducing the production cost; in addition, mother liquor after the preparation of the product is neutralized to pH 7 by 40% HBr aqueous solution, and the mother liquor is recycled by benzene with water until the water content is below 0.2%; demethylation by-product CH3Br directly reacts with sodium p-toluenesulfonate to generate p-toluenesulfonyl and NaBr, wherein the p-toluenesulfonyl is an important intermediate for preparing the medicine thiamphenicol, and the generated NaBr can be recycled and reused by treatment. The invention provides N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl]The preparation method of the methanesulfonamide is environment-friendly, simple in process, high in yield and low in cost.
The embodiment of the application provides a preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide, which comprises the following steps:
adding N- [4- (2-formamidoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide and 5-15 times of DMF (dimethyl formamide) into a reaction bottle, adding 1.5-5 times (molar ratio) of NaBr, and fully reacting at 80-150 ℃; after the reaction is finished, pouring the mixture into a proper amount of sodium sulfite solution with the mass ratio of 1 percent, generating yellow solid, performing suction filtration, washing with water, and drying in vacuum to obtain a light yellow solid compound, namely N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide, wherein the product yield is more than 90 percent.
The reaction formula is as follows:
in the above production method, the time for the sufficient reaction is generally 5 to 10 hours, preferably 7 to 9 hours;
in order to further shorten the reaction time, be beneficial to industrialized mass production and reduce the production cost, the reaction process adopts an ultrasonic technology, the reaction time is shortened from 5-10h to 10-30min, and the yield can also be improved to more than 97%.
Preferably, the ultrasonic generator is set to have a frequency of 20-60KHz, preferably 30-50 KHz;
the ratio of the reactants to the solvent is preferably as follows: n- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide: DMF ═ 1: 5-15, preferably 1: 10-13;
the proportion of the reactant and NaBr is preferably as follows: n- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide: NaBr ═ 1: 1.5-5, preferably 1: 2-3;
the reaction temperature required by the step is 80-150 ℃, preferably 120-145 ℃;
one or more technical solutions provided in the embodiments of the present application have at least the following technical effects or advantages:
the invention provides a preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide, which uses N- [4- (2-formamidoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide as a raw material, and uses NaBr/DMF to carry out demethylation reaction, so that methyl on a 5-position is selectively removed. The yield is more than 90%; the method for preparing the N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide has the advantages of environment friendliness, simple process, high yield and low cost.
Detailed Description
In order to better understand the technical solutions, the technical solutions will be described in detail with reference to specific embodiments.
The following examples are intended to further illustrate the invention and are not intended to limit the application of the invention. The percentages in the examples are uniformly mass fractions.
Example one
20g of N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonyl (manufactured by Jia Erke Biotechnology Nantong Co., Ltd.) and 250g of DMF were put into a reaction flask, and 15.5g of NaBr was further added; reacting at 140 ℃ for 7 h; after the reaction, the reaction mixture was poured into 500g of a 1% sodium sulfite solution by mass to produce a yellow solid, which was then filtered, washed with water, and dried under vacuum to obtain 17.9g of a pale yellow solid compound with a yield of 93%.
Example two
20g of N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide and 200g of DMF were added to a reaction flask, and 13.5g of NaBr were then added; reacting at 140 ℃ for 7 h; after the reaction, the reaction solution was poured into 500g of a 1% sodium sulfite solution by mass to produce a yellow solid, which was then filtered, washed with water, and dried under vacuum to obtain 17.6g of a pale yellow solid compound with a yield of 91%.
EXAMPLE III
20g of N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide and 250g of DMF were added to a reaction flask, and 15.5g of NaBr were further added. Placing the reaction bottle in an ultrasonic generator, and setting the frequency at 25 KHz; reacting at 140 ℃ for 15 min; the material was poured into 500g of 1% by mass sodium sulfite solution to produce a yellow solid, which was filtered, washed with water and dried under vacuum to give 18.7g of a pale yellow solid compound with a yield of 97.1%.
Example four
20g of N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide and 200g of DMF were charged in a reaction flask, and 13.5g of NaBr were further added. The reaction flask was placed in an ultrasonic generator with a frequency set at 40 KHz. The reaction was carried out at 120 ℃ for 25 min. The material was poured into 500g of 1% by mass sodium sulfite solution, yellow solid was produced, which was filtered, washed with water and dried under vacuum to give 19.2g of pale yellow solid compound with a yield of 99.7%.
EXAMPLE five
Mother liquor treatment: the mother liquor was neutralized with 40% aqueous HBr to pH 7 and 200g of benzene was added. Then adding the mixture into a distillation flask provided with a water diversion device, and distilling the mixture under normal pressure until no water is separated out (the distilled water can be used as process water). 198g of benzene are distilled out at normal pressure (recovered and reused). The residual mother liquor is directly applied after detecting the NaBr content and the moisture.
EXAMPLE six
CH3Utilization of Br: will demethylate the produced CH3Br was passed directly into the reaction flask. The reaction flask was charged with 9g of sodium p-toluenesulfinate, 6g of sodium bicarbonate and 30g of water and incubated at 80-90 ℃. After the addition, the reaction was kept at the temperature for 2 hours and cooled to room temperature. Filtering and vacuum drying to obtain the p-methyl phenyl sulfone. The resulting mother liquors were neutralized with 40% aqueous HBr to pH 7 and combined for workup with the mother liquor resulting from the synthesis.
The above-mentioned embodiments are merely illustrative of the technical ideas and features of the present invention, and are intended to enable those skilled in the art to understand the contents of the present invention, and not to limit the scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (10)
1. A preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide is characterized in that N- [4- (2-formamidoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide is used as a raw material, NaBr is dissolved in N, N-dimethylformamide to carry out demethylation reaction, and the N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide is prepared.
2. The method according to claim 1, wherein the preparation method comprises the following specific steps: dissolving N- [4- (2-formamidoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide in 5-15 times of DMF, adding NaBr with the molar ratio of 1.5-5 times, and fully reacting at 80-150 ℃; after the reaction is finished, the reactant is poured into a proper amount of sodium sulfite solution with the mass ratio of 1%, yellow solid is generated, and the light yellow solid compound, namely N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide is obtained after suction filtration, water washing and vacuum drying.
3. The method of claim 1, wherein the method has the following reaction formula:
4. the preparation method according to claim 2, wherein the reaction process is carried out under ultrasonic conditions for 10-30 min.
5. The method of claim 4, wherein the ultrasonic frequency is 20 to 60 KHz.
6. The method of claim 5, wherein the ultrasonic frequency is 30 to 50 KHz.
7. The process according to claim 2, wherein the mass ratio of N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide to the solvent N, N-dimethylformamide is 1: 5-15.
8. The process according to claim 2, wherein the mass ratio of N- [ 4-mono (2-formylaminoacetyl) -5-methoxy-2-phenoxyphenyl ] methanesulfonamide to NaBr is 1: 1.5-5.
9. The method of claim 2, further comprising the steps of: after the product in claim 1 is precipitated, neutralizing the residual mother liquor with 40% HBr aqueous solution until the pH is 7, and carrying water with benzene until the water content is below 0.2%; the residual mother liquor is directly applied after detecting the NaBr content and the moisture.
10. The method of claim 2, further comprising the steps of: the demethylation reaction also produces a byproduct CH3Br, by-product CH3Br directly reacts with sodium p-toluenesulfinate to generate p-toluenesulfone and NaBr.
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| CN202110579986.2A CN113527148A (en) | 2021-05-26 | 2021-05-26 | Preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide |
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| CN202110579986.2A CN113527148A (en) | 2021-05-26 | 2021-05-26 | Preparation method of N- [4- (2-formamidoacetyl) -5-hydroxy-2-phenoxyphenyl ] methanesulfonamide |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0597840A (en) * | 1991-10-11 | 1993-04-20 | Toyama Chem Co Ltd | Production of 3-acylamino-6-phenyloxy-7-alkyl sulfonylamino-4h-1-benzopyran-4-one or its salt |
| CN1462748A (en) * | 2003-06-18 | 2003-12-24 | 江苏扬子江药业集团有限公司 | Preparation of 3-(formamide)-7-(methylsulfonyl amine)-6-(phenoxy)-4H-1-(benzopyran)-4-ketone |
| CN101735190A (en) * | 2009-12-14 | 2010-06-16 | 昆明理工大学 | Method for preparing baicalein |
| CN102807515A (en) * | 2012-09-04 | 2012-12-05 | 江苏昊华精细化工有限公司 | Method for synthesizing 3-methylsulfonylamido-4-phenoxy-6-(N-formyl)amidoacetylphenol |
-
2021
- 2021-05-26 CN CN202110579986.2A patent/CN113527148A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0597840A (en) * | 1991-10-11 | 1993-04-20 | Toyama Chem Co Ltd | Production of 3-acylamino-6-phenyloxy-7-alkyl sulfonylamino-4h-1-benzopyran-4-one or its salt |
| CN1462748A (en) * | 2003-06-18 | 2003-12-24 | 江苏扬子江药业集团有限公司 | Preparation of 3-(formamide)-7-(methylsulfonyl amine)-6-(phenoxy)-4H-1-(benzopyran)-4-ketone |
| CN101735190A (en) * | 2009-12-14 | 2010-06-16 | 昆明理工大学 | Method for preparing baicalein |
| CN102807515A (en) * | 2012-09-04 | 2012-12-05 | 江苏昊华精细化工有限公司 | Method for synthesizing 3-methylsulfonylamido-4-phenoxy-6-(N-formyl)amidoacetylphenol |
Non-Patent Citations (2)
| Title |
|---|
| 余磊等: "芳基甲基醚去甲基化反应", 《广东化工》 * |
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