CN105017009A - Loxoprofen sodium synthesis method - Google Patents
Loxoprofen sodium synthesis method Download PDFInfo
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- CN105017009A CN105017009A CN201510386438.2A CN201510386438A CN105017009A CN 105017009 A CN105017009 A CN 105017009A CN 201510386438 A CN201510386438 A CN 201510386438A CN 105017009 A CN105017009 A CN 105017009A
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- loxoprofen sodium
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- 229960002373 loxoprofen Drugs 0.000 title abstract description 15
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 title abstract 5
- 238000001308 synthesis method Methods 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 abstract description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 15
- 150000001875 compounds Chemical class 0.000 abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 10
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 abstract description 6
- 229940017219 methyl propionate Drugs 0.000 abstract description 6
- 238000005265 energy consumption Methods 0.000 abstract description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract 2
- QQXBRVQJMKBAOZ-UHFFFAOYSA-N 2-[4-(bromomethyl)phenyl]propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(CBr)C=C1 QQXBRVQJMKBAOZ-UHFFFAOYSA-N 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 13
- 238000005406 washing Methods 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- WORCCYVLMMTGFR-UHFFFAOYSA-M loxoprofen sodium Chemical compound [Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 WORCCYVLMMTGFR-UHFFFAOYSA-M 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 238000010189 synthetic method Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000007670 refining Methods 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- UDSFAEKRVUSQDD-UHFFFAOYSA-N Dimethyl adipate Chemical compound COC(=O)CCCCC(=O)OC UDSFAEKRVUSQDD-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000013517 stratification Methods 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 206010034464 Periarthritis Diseases 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- 206010049590 Upper respiratory tract inflammation Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention discloses a loxoprofen sodium synthesis method. The method comprises steps of: firstly, performing a reaction among a 2-(4-bromomethylphenyl)propionic acid, concentrated sulfuric acid and methanol to obtain 2-(4-bromomethylphenyl)methyl propionate; secondly, continuing a reaction among the 2-(4-bromomethylphenyl)methyl propionate, dimethyle adipate and sodium methoxoide methanol to obtain an intermediate compound (I); thirdly, performing a reaction among the intermediate compound (I), acetate, water and concentrated sulfuric acid to obtain an intermediate compound (II); and at last, performing a reaction among the intermediate compound (II), acetone, and sodium hydroxide to obtain the loxoprofen sodium. The loxoprofen sodium synthesis method is reasonable in the whole reaction step design; and the synthesized loxoprofen sodium is good in quality, high in purity, simple in synthesis method, high in yield, low in energy consumption, and low in cost.
Description
Technical field
The present invention relates to medicine and manufacture field, specifically a kind of synthetic method of loxoprofen sodium.
Background technology
Loxoprofen sodium belongs to phenylpropionic acid non-steroid antiinflammatory drug, is that first Japanese Sankyo Co., Ltd develops, and Japan is the kind of sales volume first in NSAID (non-steroidal anti-inflammatory drug) now, and recorded by Pharmacopeia of Japan, China is import.This product has been listed country's 95 and 2010 years new product developments in and has been recommended one of trial-production kind.Loxoprofen sodium is compared with similar drugs clinically, and its feature is mainly reflected in: stronger (clinical effectiveness is good), faster (oral 30 minutes plasma concentrations and peaking), safer (side effect is little).Another kind of feature is that indication is wide, the easing pain and diminishing inflammation after can being widely used in the relieving inflammation and relaxing pain of rheumatoid arthritis, pain in the back, scapulohumeral periarthritis, neck shoulder wrist syndromes etc., operation, wound clinically and after exodontia and the antipyretic-antalgic etc. of acute upper respiratory tract inflammation.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of synthetic method of loxoprofen sodium, and its synthetic method is simple, and yield is high.
Technical scheme of the present invention is:
A synthetic method for loxoprofen sodium, includes following steps:
(1), first toluene is added in methyl alcohol, then continue to add vitriol oil ammonium, 2-(4-2-bromomethylphenyl) propionic acid under stirring, 5 ~ 6h is reacted at 20-30 DEG C, after reaction terminates, cooling reaction solution, separates organic layer, and organic layer washing, adjust ph are to 12-13, continue a point organic layer, washing, drying, filtration, concentrate, obtain 2-(4-2-bromomethylphenyl) methyl propionate;
(2), first in toluene, dimethyl adipate and dimethyl sulfoxide (DMSO) is added, stirring is cooled to 5-10 DEG C, continue to add methanol solution of sodium methylate, after temperature control reacts 1 hour, heat temperature raising, normal pressure stops when being concentrated to system temperature 120 DEG C, when then cooling reaction solution 70-80 DEG C, add dimethyl formamide, after continuing to be cooled to 5-10 DEG C, add 2-(4-2-bromomethylphenyl) methyl propionate, and then 20-25 DEG C of reaction, after having reacted, reaction solution, after a point organic layer, washing, concentrating, obtains the transparent liquid of compound (I);
(3), the heating of compound (I), acetic acid, water and the vitriol oil, normal pressure are concentrated, be warmed up to 120-130 DEG C of reaction 2 hours, then reaction solution is cooled to 60 DEG C, Depressor response, temperature of reaction 50-60 DEG C, reaction 2-3 hour, react rear reaction solution and stir extraction, layering, washing, crystallization, filter to obtain the thick wet product of compound (II), thick wet product joins heating for dissolving in toluene, be cooled to 5-10 DEG C after dissolving completes, filter and drain to obtain the refining wet product of compound (II);
(4), the refining wet product of compound (II) is joined stirring and dissolving in acetone, sodium hydroxide solution is added at 30-40 DEG C after having dissolved, until system is aobvious neutral, then heat up and to ensure in reaction solution without solid, proceed to decolour, filter, wash dry must loxoprofen sodium crystal;
Adjust ph in described step (1) selects salt of wormwood.
In described step (2), the mass concentration of methanol solution of sodium methylate is 35%; The reaction solution be obtained by reacting in described step (2) stirs after adding water and toluene, stratification, and uses water, hydrochloric acid soln, sodium hydroxide solution, salt solution, water washing successively.
The reaction solution be obtained by reacting in described step (3) adds toluene and water stirs extraction, separates organic layer after leaving standstill, and after organic layer washing, adjust ph is 5.5-6.5, organic layer washs again, be cooled to 5-10 DEG C, keep more than 8h crystallization, filter and obtain thick wet product.
The reaction solution be obtained by reacting in described step (4) adopts activated carbon decolorizing, adopts washing with acetone.
Advantage of the present invention:
The loxoprofen sodium quality of the present invention's synthesis is good, and purity is high, and synthetic method is simple, and yield is high, less energy consumption, and cost is low.
Embodiment
A synthetic method for loxoprofen sodium, is characterized in that: include following steps:
(1), first toluene is added in methyl alcohol, then continue to add vitriol oil ammonium, 2-(4-2-bromomethylphenyl) propionic acid under stirring, 5 ~ 6h is reacted at 20-30 DEG C, after reaction terminates, cooling reaction solution, separates organic layer, and organic layer washing, salt of wormwood adjust ph are to 12-13, continue a point organic layer, washing, drying, filtration, concentrate, obtain 2-(4-2-bromomethylphenyl) methyl propionate;
(2), first in toluene, dimethyl adipate and dimethyl sulfoxide (DMSO) is added, stirring is cooled to 5-10 DEG C, continue to add the methanol solution of sodium methylate that mass concentration is 35%, after temperature control reacts 1 hour, heat temperature raising, normal pressure stops when being concentrated to system temperature 120 DEG C, when then cooling reaction solution 70-80 DEG C, add dimethyl formamide, after continuing to be cooled to 5-10 DEG C, add 2-(4-2-bromomethylphenyl) methyl propionate, and then 20-25 DEG C of reaction, after having reacted, reaction solution stirs after adding water and toluene, stratification, and use water successively, hydrochloric acid soln, sodium hydroxide solution, salt solution, water washing, after concentrated toluene, obtain the light yellow clear liquid of compound (I),
(3), by compound (I), acetic acid, water and vitriol oil heating, normal pressure concentrates, be warmed up to 120-130 DEG C of reaction 2 hours, then reaction solution is cooled to 60 DEG C, Depressor response, temperature of reaction 50-60 DEG C, reaction 2-3 hour, react rear reaction solution and add toluene and water stirring extraction, organic layer is separated after leaving standstill, after organic layer washing, adjust ph is 5.5-6.5, organic layer washs again, be cooled to 5-10 DEG C, keep more than 8h crystallization, filtration obtains the thick wet product of compound (II), thick wet product joins heating for dissolving in toluene, 5-10 DEG C is cooled to after dissolving completes, the refining wet product of compound (II) is drained to obtain in filtration,
(4), the refining wet product of compound (II) is joined stirring and dissolving in acetone, sodium hydroxide solution is added at 30-40 DEG C after having dissolved, until system is aobvious neutral, then heat up and to ensure in reaction solution without solid, proceed activated carbon decolorizing decolouring, filtration, washing with acetone, dry must loxoprofen sodium crystal;
Claims (5)
1. a synthetic method for loxoprofen sodium, is characterized in that: include following steps:
(1), first toluene is added in methyl alcohol, then continue to add vitriol oil ammonium, 2-(4-2-bromomethylphenyl) propionic acid under stirring, 5 ~ 6h is reacted at 20-30 DEG C, after reaction terminates, cooling reaction solution, separates organic layer, and organic layer washing, adjust ph are to 12-13, continue a point organic layer, washing, drying, filtration, concentrate, obtain 2-(4-2-bromomethylphenyl) methyl propionate;
(2), first in toluene, dimethyl adipate and dimethyl sulfoxide (DMSO) is added, stirring is cooled to 5-10 DEG C, continue to add methanol solution of sodium methylate, after temperature control reacts 1 hour, heat temperature raising, normal pressure stops when being concentrated to system temperature 120 DEG C, when then cooling reaction solution 70-80 DEG C, add dimethyl formamide, after continuing to be cooled to 5-10 DEG C, add 2-(4-2-bromomethylphenyl) methyl propionate, and then 20-25 DEG C of reaction, after having reacted, reaction solution, after a point organic layer, washing, concentrating, obtains the transparent liquid of compound (I);
(3), the heating of compound (I), acetic acid, water and the vitriol oil, normal pressure are concentrated, be warmed up to 120-130 DEG C of reaction 2 hours, then reaction solution is cooled to 60 DEG C, Depressor response, temperature of reaction 50-60 DEG C, reaction 2-3 hour, react rear reaction solution and stir extraction, layering, washing, crystallization, filter to obtain the thick wet product of compound (II), thick wet product joins heating for dissolving in toluene, be cooled to 5-10 DEG C after dissolving completes, filter and drain to obtain the refining wet product of compound (II);
(4), the refining wet product of compound (II) is joined stirring and dissolving in acetone, sodium hydroxide solution is added at 30-40 DEG C after having dissolved, until system is aobvious neutral, then heat up and to ensure in reaction solution without solid, proceed to decolour, filter, wash dry must loxoprofen sodium crystal;
2. the synthetic method of a kind of loxoprofen sodium according to claim 1, is characterized in that: the adjust ph in described step (1) selects salt of wormwood.
3. the synthetic method of a kind of loxoprofen sodium according to claim 1, is characterized in that: in described step (2), the mass concentration of methanol solution of sodium methylate is 35%; The reaction solution be obtained by reacting in described step (2) stirs after adding water and toluene, stratification, and uses water, hydrochloric acid soln, sodium hydroxide solution, salt solution, water washing successively.
4. the synthetic method of a kind of loxoprofen sodium according to claim 1, it is characterized in that: the reaction solution be obtained by reacting in described step (3) adds toluene and water stirs extraction, organic layer is separated after leaving standstill, after organic layer washing, adjust ph is 5.5-6.5, organic layer washs again, be cooled to 5-10 DEG C, keep more than 8h crystallization, filter and obtain thick wet product.
5. the synthetic method of a kind of loxoprofen sodium according to claim 1, is characterized in that: the reaction solution be obtained by reacting in described step (4) adopts activated carbon decolorizing, adopts washing with acetone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510386438.2A CN105017009A (en) | 2015-06-29 | 2015-06-29 | Loxoprofen sodium synthesis method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510386438.2A CN105017009A (en) | 2015-06-29 | 2015-06-29 | Loxoprofen sodium synthesis method |
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| CN105017009A true CN105017009A (en) | 2015-11-04 |
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| CN201510386438.2A Pending CN105017009A (en) | 2015-06-29 | 2015-06-29 | Loxoprofen sodium synthesis method |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105601500A (en) * | 2016-03-07 | 2016-05-25 | 山东罗欣药业集团股份有限公司 | Loxoprofen-sodium sesquialter hydrate crystal form and preparing method thereof |
| CN108440274A (en) * | 2018-03-06 | 2018-08-24 | 大桐制药（中国）有限责任公司 | A kind of synthetic method of high-purity nonsteroidal anti-inflammatory drug loxoprofen sodium |
| CN108586233A (en) * | 2017-12-12 | 2018-09-28 | 湖北迅达药业股份有限公司 | The method for synthesizing 2- (4 ' -2-bromomethylphenyl) propionic ester |
| WO2019047654A1 (en) * | 2017-09-07 | 2019-03-14 | 江苏瑞科医药科技有限公司 | Method for preparing substituted phenylacetic acid derivative |
| CN110746290A (en) * | 2019-11-11 | 2020-02-04 | 威海厚普生物科技有限公司 | Novel salt forming method of high-purity loxoprofen sodium |
| CN111440059A (en) * | 2020-05-14 | 2020-07-24 | 上海柏狮生物科技有限公司 | Synthetic method of loxoprofen |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101412670A (en) * | 2007-10-19 | 2009-04-22 | 浙江普洛医药科技有限公司 | Method for synthesizing loxoprofen sodium |
| CN104326903A (en) * | 2014-10-14 | 2015-02-04 | 合肥远志医药科技开发有限公司 | Industrial production method of high purity loxoprofen sodium dehydrate |
-
2015
- 2015-06-29 CN CN201510386438.2A patent/CN105017009A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101412670A (en) * | 2007-10-19 | 2009-04-22 | 浙江普洛医药科技有限公司 | Method for synthesizing loxoprofen sodium |
| CN104326903A (en) * | 2014-10-14 | 2015-02-04 | 合肥远志医药科技开发有限公司 | Industrial production method of high purity loxoprofen sodium dehydrate |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105601500A (en) * | 2016-03-07 | 2016-05-25 | 山东罗欣药业集团股份有限公司 | Loxoprofen-sodium sesquialter hydrate crystal form and preparing method thereof |
| WO2019047654A1 (en) * | 2017-09-07 | 2019-03-14 | 江苏瑞科医药科技有限公司 | Method for preparing substituted phenylacetic acid derivative |
| EP3680227A4 (en) * | 2017-09-07 | 2021-06-02 | Jiangsu Ruike Medical Science And Technology Co., Ltd. | Method for preparing substituted phenylacetic acid derivative |
| CN108586233A (en) * | 2017-12-12 | 2018-09-28 | 湖北迅达药业股份有限公司 | The method for synthesizing 2- (4 ' -2-bromomethylphenyl) propionic ester |
| CN108586233B (en) * | 2017-12-12 | 2021-05-18 | 湖北迅达药业股份有限公司 | Method for synthesizing 2-(4'-bromomethylphenyl) propionate |
| CN108440274A (en) * | 2018-03-06 | 2018-08-24 | 大桐制药（中国）有限责任公司 | A kind of synthetic method of high-purity nonsteroidal anti-inflammatory drug loxoprofen sodium |
| CN110746290A (en) * | 2019-11-11 | 2020-02-04 | 威海厚普生物科技有限公司 | Novel salt forming method of high-purity loxoprofen sodium |
| CN111440059A (en) * | 2020-05-14 | 2020-07-24 | 上海柏狮生物科技有限公司 | Synthetic method of loxoprofen |
| CN111440059B (en) * | 2020-05-14 | 2022-11-15 | 上海柏狮生物科技有限公司 | Synthetic method of loxoprofen |
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