CN103304453A - Method for synthesizing 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid in two steps - Google Patents
Method for synthesizing 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid in two steps Download PDFInfo
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Abstract
The invention discloses a method for synthesizing 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid in two steps. The method comprises the following steps of: (a) reacting 2-methoxy-4-acetaminomethyl benzoate with chlorosulfonic acid for 6-9 hours in a reactor and then carrying out hydrolysis separation to obtain 2-methoxy-4-acetamino-5-sulfonylchloromethyl benzoate; and (b) reacting the obtained 2-methoxy-4-acetamino-5-sulfonylchloromethyl benzoate with sodium sulfite and diethyl sulfate for 6-9 hours under the reflux condition and finally carrying out the operations such as aciding out with hydrochloric acid to obtain the target product 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid, wherein the mole ratio of 2-methoxy-4-acetaminomethyl benzoate to chlorosulfonic acid is 1:(5-8); and the mole ratio of 2-methoxy-4-acetamino-5-sulfonylchloromethyl benzoate to sodium sulfite to diethyl sulfate is 1:(4-6):(2-3). The method has the advantages that the process route is simple; the product yield is high; the total yield can reach 75%; the purity reaches 99.5%; the product has good quality and white appearance; the defects of long synthetic route, low yield, poor product quality and the like in the original processes are overcome so that the method is more suitable for industrial production requirements; and a new method is provided for synthesizing 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid.
Description
Technical field
The present invention relates to the synthetic method of organic compound, specifically, is the synthetic 2-methoxyl group of two-step approach-4-amino-5-ethyl sulfone phenylformic acid.
Background technology
2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid claims 4-amino-5-(ethylsulfonyl)-O-Anisic Acid, Ah rice's acid or 2-methoxyl group-4-amino-5-ethylsulfonyl phenylformic acid again, molecular formula: C
10H
13NO
5S, molecular weight: 259.28, it is the important intermediate of synthetic antipsychotic drug amisulpride (amisulpride).
Report about 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid synthetic route is a lot, and the main route of suitability for industrialized production utilization at present is:
This route is to get target product (6) with 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester (1) through deacetylation, thiocyanation, ethylization, oxidation, alkaline hydrolysis, and through the reaction of 5 steps, but it is low respectively to go on foot yield, and second-rate, empirical tests, total recovery about 45%.The by product that produces in the thiocyanation process takes in the finished product always, is difficult to remove, and the product that obtains is light yellow, still can't transfer white to through purifying repeatedly, and it is about 98% that HPLC records 2-methoxyl group-4-amino-benzoic purity of 5-ethyl sulfone.
Summary of the invention
The objective of the invention is, shortcomings such as yield low, poor product quality long at operational path in the prior art, provide a kind of two-step approach to synthesize 2-methoxyl group-4-amino-benzoic method of 5-ethyl sulfone.
For achieving the above object, the technical scheme taked of the present invention is:
Two-step approach is synthesized 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid, may further comprise the steps:
(a) 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester and chlorsulfonic acid were reacted in reactor 6～9 hours with mol ratio 1:5～8, the hydrolysis separation obtains 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate then;
(b) join the 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate that obtains in the aqueous solution that contains S-WAT and be incubated 1 hour, in reaction solution, drip ethyl sulfate again after the cooling, under refluxad reacted 6～9 hours, obtain purpose product 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid finally by hydrochloric acid acid out, ultrapure water dissolving rear decoloring, recrystallization, drying, the mol ratio of described 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, S-WAT and ethyl sulfate is 1:4～6:2～3.Reaction equation is:
Wherein (1) is 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester, and (2) are 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, and (3) are 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid.
The temperature of reaction of the 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester described in the step (a) and chlorsulfonic acid is 5～10 ℃.
2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester described in the step (a) and the mol ratio of chlorsulfonic acid are preferably 1:6～7.
2-methoxyl group described in the step (b)-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate and S-WAT holding temperature are 75～80 ℃.
The temperature of reaction solution is 35～40 ℃ during dropping ethyl sulfate described in the step (b).
The condition of the hydrochloric acid acid out described in the step (b) is: control reaction solution 40 ℃ of following dripping hydrochloric acid to reaction solution pH be 2～3.
The weight ratio of ultrapure water and reaction product is 10 times in the ultrapure water dissolving step described in the step (b).
Decolouring described in the step (b) is activated carbon decolorizing, and described drying is 60 ℃ of vacuum-dryings.
The mol ratio of the 2-methoxyl group described in the step (b)-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, S-WAT and ethyl sulfate is preferably 1:5:2～3.
The mol ratio of the 2-methoxyl group described in the step (b)-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, S-WAT and ethyl sulfate is 1:5:2.5 more preferably.
The invention has the advantages that:
The inventive method is to get target product by 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester through two-step reaction, and operational path is simple, the product yield height, and total recovery can reach 75%, and purity reaches 99.5%, and good product quality and outward appearance are white; Solve shortcomings such as synthetic route is long in the former technology, yield is low, poor product quality, be more suitable for the suitability for industrialized production requirement; For synthetic 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid provides a kind of new method.
Embodiment
Below embodiment provided by the invention is elaborated.
Embodiment 1
With 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester 201g(0.9mol) slowly be added to and contain chlorsulfonic acid 839g(7.2mol below 10 ℃) in the 1000mL four-hole reaction flask of band chlorination absorption system, reinforced process control is below 10 ℃, reinforced finishing reacted 6 hours down at 5～10 ℃.Reaction finishes, and reaction solution is poured in 1500 milliliters the frozen water, and solid is separated out, and suction filtration gets the wet product 277g of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, moisture 10.6%, product 247.7g(0.77mol gives money as a gift), molar yield is 85.6%.The wet product of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate are added to 75～80 ℃ in batches contain S-WAT 582g(4.62mol) 2000 milliliters of four-hole reaction flasks taking back flow condenser of the 1500mL aqueous solution in, the reinforced insulation 1 hour that finishes.Be cooled to 35～40 ℃ then, and keep this temperature slowly to drip ethyl sulfate 355.7g(2.3mol), ethyl sulfate dropwises, and is warming up to backflow, and keeps reacting 9 hours under the reflux state.Reaction finishes, be cooled to below 40 ℃, and 40 ℃ of following dripping hydrochloric acid of control reaction solution to reaction solution pH be 2～3.Further reaction solution being cooled to suction filtration below 15 ℃ separates, the wet product of reaction product are with the ultrapure water rising temperature for dissolving of 10 times of weight ratios, being cooled to suction filtration below 15 ℃ behind the activated carbon decolorizing separates, last 60 ℃ of vacuum-dryings get 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid 173.7g(0.67mol), this step molar yield is 87.01%.Be reacted to 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid from 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester, total molar yield is 74.48%, and product is white crystals, and methoxyl group-4-amino-benzoic content of 5-ethyl sulfone is 99.71% to detect 2-through HPLC.The HPLC testing conditions is: moving phase is potassium phosphate buffer: acetonitrile=80:20(V/V), the mass concentration of potassium primary phosphate is 6.8g/L in the potassium phosphate buffer, and damping fluid is transferred pH=3.3 with phosphoric acid; The C18 chromatographic column, the detection wavelength is 230nm, and flow velocity is 1.5mL/min, and the 0.01g sample is diluted to 25 milliliters with moving phase, and sample size is 5 μ L.
Embodiment 2
With 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester 100.5g(0.45mol) slowly be added to and contain chlorsulfonic acid 262g(2.25mol below 10 ℃) in the 1000mL four-hole reaction flask of band chlorination absorption system, reinforced process control is below 10 ℃, reinforced finishing reacted 8 hours down at 5～10 ℃.Reaction finishes, and reaction solution is poured in 800 milliliters the frozen water, and solid is separated out, and suction filtration gets the wet product 144.6g of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, moisture 13.2%, product 125.5g(0.39mol gives money as a gift), molar yield is 86.4%.The wet product of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate are added to 75～80 ℃ in batches contain S-WAT 245.8g(1.95mol) 2000 milliliters of four-hole reaction flasks taking back flow condenser of the 600mL aqueous solution in, the reinforced insulation 1 hour that finishes.Be cooled to 35～40 ℃ then, and keep this temperature slowly to drip ethyl sulfate 151g(0.98mol), ethyl sulfate dropwises, and is warming up to backflow, and keeps reacting 8 hours under the reflux state.Reaction finishes, be cooled to below 40 ℃, and 40 ℃ of following dripping hydrochloric acid of control reaction solution to reaction solution pH be 2～3.Further reaction solution being cooled to suction filtration below 15 ℃ separates, the wet product of reaction product are with the ultrapure water rising temperature for dissolving of 10 times of weight ratios, being cooled to suction filtration below 15 ℃ behind the activated carbon decolorizing separates, last 60 ℃ of vacuum-dryings get 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid 90.7g(0.35mol), this step molar yield is 89.7%.Be reacted to 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid from 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester, total molar yield is 77.7%, product is white crystals, and detecting 2-methoxyl group-4-amino-benzoic content of 5-ethyl sulfone through HPLC is that 99.53%, HPLC detects with embodiment 1.
Embodiment 3
With 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester 150g(0.67mol) slowly be added to and contain chlorsulfonic acid 391g(3.36mol below 10 ℃) in the 1000mL four-hole reaction flask of band chlorination absorption system, reinforced process control is below 10 ℃, reinforced finishing reacted 7 hours down at 5～10 ℃.Reaction finishes, and reaction solution is poured in 1000 milliliters the frozen water, and solid is separated out, and suction filtration gets the wet product 220.6g of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, moisture 12.4%, product 193.2g(0.60mol gives money as a gift), molar yield is 89.6%.The wet product of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate are added to 75～80 ℃ in batches contain S-WAT 302.5g(2.4mol) 2000 milliliters of four-hole reaction flasks taking back flow condenser of the 800mL aqueous solution in, the reinforced insulation 1 hour that finishes.Be cooled to 35～40 ℃ then, and keep this temperature slowly to drip ethyl sulfate 184.8g(1.2mol), ethyl sulfate dropwises, and is warming up to backflow, and keeps reacting 6 hours under the reflux state.Reaction finishes, be cooled to below 40 ℃, and 40 ℃ of following dripping hydrochloric acid of control reaction solution to reaction solution pH be 2～3.Further reaction solution being cooled to suction filtration below 15 ℃ separates, the wet product of reaction product are with the ultrapure water rising temperature for dissolving of 10 times of weight ratios, being cooled to suction filtration below 15 ℃ behind the activated carbon decolorizing separates, last 60 ℃ of vacuum-dryings get 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid 129.6g(0.5mol), this step molar yield is 83.3%.Be reacted to 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid from 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester, total molar yield is 74.6%, product is white crystals, and detecting 2-methoxyl group-4-amino-benzoic content of 5-ethyl sulfone through HPLC is that 99.63%, HPLC detects with embodiment 1.
Embodiment 4
With 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester 201g(0.9mol) slowly be added to and contain chlorsulfonic acid 681.5g(5.85mol below 10 ℃) in the 1000mL four-hole reaction flask of band chlorination absorption system, reinforced process control is below 10 ℃, reinforced finishing reacted 9 hours down at 5～10 ℃.Reaction finishes, and reaction solution is poured in 1200 milliliters the frozen water, and solid is separated out, and suction filtration gets the wet product 288.7g of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, moisture 10.9%, product 257.2g(0.8mol gives money as a gift), molar yield is 88.9%.The wet product of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate are added to 75～80 ℃ in batches contain S-WAT 403.2g(3.2mol) 2000 milliliters of four-hole reaction flasks taking back flow condenser of the 1100mL aqueous solution in, the reinforced insulation 1 hour that finishes.Be cooled to 35～40 ℃ then, and keep this temperature slowly to drip ethyl sulfate 308g(2mol), ethyl sulfate dropwises, and is warming up to backflow, and keeps reacting 9 hours under the reflux state.Reaction finishes, be cooled to below 40 ℃, and 40 ℃ of following dripping hydrochloric acid of control reaction solution to reaction solution pH be 2～3.Further reaction solution being cooled to suction filtration below 15 ℃ separates, the wet product of reaction product are with the ultrapure water rising temperature for dissolving of 10 times of weight ratios, being cooled to suction filtration below 15 ℃ behind the activated carbon decolorizing separates, last 60 ℃ of vacuum-dryings get 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid 177.8g(0.6858mol), this step molar yield is 85.7%.Be reacted to 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid from 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester, total molar yield is 76.2%, product is white crystals, and detecting 2-methoxyl group-4-amino-benzoic content of 5-ethyl sulfone through HPLC is that 99.75%, HPLC detects with embodiment 1.
Embodiment 5
With 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester 100.5g(0.45mol) slowly be added to and contain chlorsulfonic acid 366.9g(3.15mol below 10 ℃) in the 1000mL four-hole reaction flask of band chlorination absorption system, reinforced process control is below 10 ℃, reinforced finishing reacted 7.5 hours down at 5～10 ℃.Reaction finishes, and reaction solution is poured in 1300 milliliters the frozen water, and solid is separated out, and suction filtration gets the wet product 145.87g of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, moisture 12.8%, product 127.2g(0.395mol gives money as a gift), molar yield is 87.9%.The wet product of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate are added to 75～80 ℃ in batches contain S-WAT 248.85g(1.975mol) 2000 milliliters of four-hole reaction flasks taking back flow condenser of the 1300mL aqueous solution in, the reinforced insulation 1 hour that finishes.Be cooled to 35～40 ℃ then, and keep this temperature slowly to drip ethyl sulfate 121.66g(0.79mol), ethyl sulfate dropwises, and is warming up to backflow, and keeps reacting 7 hours under the reflux state.Reaction finishes, be cooled to below 40 ℃, and 40 ℃ of following dripping hydrochloric acid of control reaction solution to reaction solution pH be 2～3.Further reaction solution being cooled to suction filtration below 15 ℃ separates, the wet product of reaction product are with the ultrapure water rising temperature for dissolving of 10 times of weight ratios, being cooled to suction filtration below 15 ℃ behind the activated carbon decolorizing separates, last 60 ℃ of vacuum-dryings get 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid 87.38g(0.337mol), this step molar yield is 85.3%.Be reacted to 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid from 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester, total molar yield is 74.9%, product is white crystals, and detecting 2-methoxyl group-4-amino-benzoic content of 5-ethyl sulfone through HPLC is that 99.68%, HPLC detects with embodiment 1.
Embodiment 6
With 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester 150g(0.67mol) slowly be added to and contain chlorsulfonic acid 468.3g(4.02mol below 10 ℃) in the 1000mL four-hole reaction flask of band chlorination absorption system, reinforced process control is below 10 ℃, reinforced finishing reacted 7 hours down at 5～10 ℃.Reaction finishes, and reaction solution is poured in 1100 milliliters the frozen water, and solid is separated out, and suction filtration gets the wet product 213.1g of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, moisture 11%, product 189.68g(0.59mol gives money as a gift), molar yield is 88.05%.The wet product of 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate are added to 75～80 ℃ in batches contain S-WAT 371.7g(2.95mol) 2000 milliliters of four-hole reaction flasks taking back flow condenser of the 1000mL aqueous solution in, the reinforced insulation 1 hour that finishes.Be cooled to 35～40 ℃ then, and keep this temperature slowly to drip ethyl sulfate 272.5g(1.77mol), ethyl sulfate dropwises, and is warming up to backflow, and keeps reacting 7.5 hours under the reflux state.Reaction finishes, be cooled to below 40 ℃, and 40 ℃ of following dripping hydrochloric acid of control reaction solution to reaction solution pH be 2～3.Further reaction solution being cooled to suction filtration below 15 ℃ separates, the wet product of reaction product are with the ultrapure water rising temperature for dissolving of 10 times of weight ratios, being cooled to suction filtration below 15 ℃ behind the activated carbon decolorizing separates, last 60 ℃ of vacuum-dryings get 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid 130.46g(0.503mol), this step molar yield is 85.25%.Be reacted to 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid from 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester, total molar yield is 75.1%, product is white crystals, and detecting 2-methoxyl group-4-amino-benzoic content of 5-ethyl sulfone through HPLC is that 99.59%, HPLC detects with embodiment 1.
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the inventive method; can also make some improvement and replenish, these improvement and replenish and also should be considered as protection scope of the present invention.
Claims (10)
1. the synthetic 2-methoxyl group of two-step approach-4-amino-5-ethyl sulfone phenylformic acid is characterized in that, may further comprise the steps:
(a) 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester and chlorsulfonic acid were reacted in reactor 6～9 hours with mol ratio 1:5～8, the hydrolysis separation obtains 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate then;
(b) join the 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate that obtains in the aqueous solution that contains S-WAT and be incubated 1 hour, in reaction solution, drip ethyl sulfate again after the cooling, under refluxad reacted 6～9 hours, obtain purpose product 2-methoxyl group-4-amino-5-ethyl sulfone phenylformic acid finally by hydrochloric acid acid out, ultrapure water dissolving rear decoloring, recrystallization, drying, the mol ratio of described 2-methoxyl group-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, S-WAT and ethyl sulfate is 1:4～6:2～3.
2. synthetic method according to claim 1 is characterized in that, the temperature of reaction of the 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester described in the step (a) and chlorsulfonic acid is 5～10 ℃.
3. synthetic method according to claim 1 is characterized in that, the mol ratio of the 2-methoxyl group-4-acetyl-amino-benzoic acid methyl ester described in the step (a) and chlorsulfonic acid is 1:6～7.
4. synthetic method according to claim 1 is characterized in that, the 2-methoxyl group described in the step (b)-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate and S-WAT holding temperature are 75～80 ℃.
5. synthetic method according to claim 1 is characterized in that, the temperature of reaction solution is 35～40 ℃ during dropping ethyl sulfate described in the step (b).
6. synthetic method according to claim 1 is characterized in that, the condition of the hydrochloric acid acid out described in the step (b) is: control reaction solution 40 ℃ of following dripping hydrochloric acid to reaction solution pH be 2～3.
7. synthetic method according to claim 1 is characterized in that, the weight ratio of ultrapure water and reaction product is 10 times in the ultrapure water dissolving step described in the step (b).
8. synthetic method according to claim 1 is characterized in that, the decolouring described in the step (b) is activated carbon decolorizing, and described drying is 60 ℃ of vacuum-dryings.
9. synthetic method according to claim 1 is characterized in that, the mol ratio of the 2-methoxyl group described in the step (b)-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, S-WAT and ethyl sulfate is 1:5:2～3.
10. synthetic method according to claim 1 is characterized in that, the mol ratio of the 2-methoxyl group described in the step (b)-4-acetylaminohydroxyphenylarsonic acid 5-sulfuryl chlorio methyl benzoate, S-WAT and ethyl sulfate is 1:5:2.5.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4294828A (en) * | 1978-01-20 | 1981-10-13 | Societe D'etudes Scientifiques Et Industrielles De L'ile De-France | New derivatives of 4-amino-5-alkyl sulphonyl orthoanisamides, methods of preparing them and their application as psychotropic agents |
| EP0055524A2 (en) * | 1980-12-12 | 1982-07-07 | Beecham Group Plc | Bicyclo (3,2,1) octylbenzamides, a process for their preparation and pharmaceutical compositions containing them |
| CN101628886A (en) * | 2009-08-25 | 2010-01-20 | 北京紫萌同达科技有限公司 | Synthesis method for 2- methoxyl-4-amino-5-ethylsulfonylbenzoic acid |
-
2013
- 2013-06-18 CN CN2013102409738A patent/CN103304453A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4294828A (en) * | 1978-01-20 | 1981-10-13 | Societe D'etudes Scientifiques Et Industrielles De L'ile De-France | New derivatives of 4-amino-5-alkyl sulphonyl orthoanisamides, methods of preparing them and their application as psychotropic agents |
| EP0055524A2 (en) * | 1980-12-12 | 1982-07-07 | Beecham Group Plc | Bicyclo (3,2,1) octylbenzamides, a process for their preparation and pharmaceutical compositions containing them |
| CN101628886A (en) * | 2009-08-25 | 2010-01-20 | 北京紫萌同达科技有限公司 | Synthesis method for 2- methoxyl-4-amino-5-ethylsulfonylbenzoic acid |
Non-Patent Citations (2)
| Title |
|---|
| 李付刚，等: "2－甲氧基－4－氨基－5－乙砜基苯甲酸的合成", 《精细与专用化学品》, vol. 16, no. 13, 6 July 2008 (2008-07-06), pages 16 - 17 * |
| 程玉红，等: "氨磺必利的合成", 《中国医药工业杂志》, vol. 42, no. 11, 31 December 2011 (2011-12-31), pages 801 - 803 * |
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Application publication date: 20130918 |