CN109096229A - A kind of synthetic method of dexketoprofen intermediate - Google Patents
A kind of synthetic method of dexketoprofen intermediate Download PDFInfo
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- CN109096229A CN109096229A CN201810991647.3A CN201810991647A CN109096229A CN 109096229 A CN109096229 A CN 109096229A CN 201810991647 A CN201810991647 A CN 201810991647A CN 109096229 A CN109096229 A CN 109096229A
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- dexketoprofen
- compound
- synthetic method
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- 229960002783 dexketoprofen Drugs 0.000 title claims abstract description 21
- DKYWVDODHFEZIM-NSHDSACASA-N dexketoprofen Chemical compound OC(=O)[C@@H](C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-NSHDSACASA-N 0.000 title claims abstract description 21
- 238000010189 synthetic method Methods 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 7
- 235000019441 ethanol Nutrition 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- -1 1- methyl-1-phenyl-ethyl Chemical group 0.000 claims description 4
- 238000005360 mashing Methods 0.000 claims description 3
- PPNGALBGZJBTRY-UHFFFAOYSA-N 1-(3-benzoylphenyl)ethanone Chemical compound CC(=O)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 PPNGALBGZJBTRY-UHFFFAOYSA-N 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 10
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000011079 streamline operation Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007788 liquid Substances 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 6
- 229960000991 ketoprofen Drugs 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000006340 racemization Effects 0.000 description 3
- 239000012266 salt solution Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 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 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010041277 Sodium retention Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/48—Compounds containing oxirane rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to pharmaceutical technology fields, more particularly to a kind of synthetic method of dexketoprofen intermediate, the intermediate of dexketoprofen is prepared using the asymmetric syntheses that Darzens reacts, this method can be improved the selectivity of reaction, reduce the loss of raw material, yield and streamline operation are improved, industrialized production is advantageously implemented.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of synthetic method of dexketoprofen intermediate.
Background technique
Mixed Ketoprofen is made of the dexketoprofen and left-handed Ketoprofen of equivalent, as anti-inflammatory and antalgesic clinical application
It is 30 years existing, it is considered to be safest non-steroid anti-inflammatory drug NSAID, and be a kind of non-prescribed medicine.But mixed ketone Lip river
Sweet smell still has and reduces including gastrointestinal toxicity, water-sodium retention, renal perfusion and a variety of side reactions such as allergic reaction, and incidence is up to 15%
~30%.To develop safer NSAID, two kinds of drugs are recommended: the pure sky of Cycloxygenase (COX-2) inhibitor and NSAID
Between corresponding body, especially dexketoprofen.1996, dexketoprofen started to be widely used in treatment rheumatoid pass in Austria
Section is scorching, and since it is the pure space corresponding body of Ketoprofen, and people have a large amount of clinical experiences to Ketoprofen, thus quickly by
Receive approval.
Before the present invention, there is the synthetic method of more document report Ketoprofens, such as patent CN 101928214B, this be by
Compound (1) 3- acetyl Benzophenone obtains the Ketoprofen of racemization after reacting with ethyl chloroacetate.Synthetic route is as follows:
Patent CN 16631772A, oxidation obtains racemization after synthesizing compound (3) 3- benzoyl-Alpha-Methyl benzyl carbinol
Ketoprofen, synthetic route are as follows:
Obtaining the common method of dexketoprofen at present is using dextrose octylame and Ketoprofen at splitting after salt, such as patent CN
Described in 101928214 B.The patent using the fractionation of circulating sleeve usage, racemization, the method that splits prepares raceme again.It presses
The dexketoprofen yield that method is prepared like this is below 70%, and material loss is larger, cumbersome, is unfavorable for work
Industry mass production.
Summary of the invention:
The object of the invention is place against the above deficiency, provides a kind of synthesis side of chiral dexketoprofen intermediate
Method.With the asymmetric syntheses starting point that Darzens reacts, compound (1) and compound (2) is subjected to the conjunction of Darzens asymmetry
At obtained dexketoprofen intermediate, this method can be improved the selectivity of reaction, reduce the loss of raw material, improve yield and letter
Change operating process, is advantageously implemented industrialized production.Dexketoprofen is further prepared by the intermediate.
It was found that with compound (2) asymmetric D arzens occurs under alkaline condition for compound (1) reacts in research
It is made with chiral α, beta epoxide acid esters.
There is chiral three-membered ring using generation, be hydrolyzed, decarboxylation, oxidation, purity higher dextrorotation ketone Lip river be made
Fragrant intermediate.
Summary of the invention the following steps are included:
By compound (1), compound (2) is mixed with methylene chloride, stirring cooling, addition potassium tert-butoxide, and -20 DEG C~0 DEG C
Under the conditions of react；Water is slowly added dropwise after fully reacting, divides and takes organic phase, saturated common salt water washing is added to anhydrous sulphur to organic
Sour sodium is dry, filters, and filtrate decompression concentration obtains product, and with ethyl alcohol, acetone soln mixing, mashing is filtered to obtain the final product.
Compound (1) and compound (2) molar ratio are 0.8~1.1:1, preferably 0.9:1.
Methylene chloride and the mass ratio of compound (2) are 10~25:1, preferably 20:1.
Stirring is cooled to -30 DEG C~-10 DEG C, and temperature is preferably -10 DEG C.
Potassium tert-butoxide and the mass ratio of compound (2) are 1:2~3, preferably 1:2.5.
It is filtered after the dry 20min~3h of anhydrous sodium sulfate is added, drying time preferred 1h.
The product being concentrated under reduced pressure to give after drying, after being mixed with ethyl alcohol, acetone soln, mashing temperature be 30 DEG C~
50 DEG C, preferably 40 DEG C；Beating time is 1h~3h, preferably 2h.
Specific embodiment:
The preparation of dexketoprofen intermediate:
Embodiment one:
Compound (1) 8.67g (0.0389mol) and compound (2) 15.00g (0.0486mol) are dissolved in methylene chloride
In 300ml, nitrogen protection.- 30 DEG C are cooled under stirring condition, potassium tert-butoxide 6.00g is inwardly added, temperature control -10~-5 DEG C are anti-
Answer 3h.Water is slowly added dropwise after fully reacting under the conditions of 0 DEG C, is stood after stirring 1h, liquid separation liquid separation takes organic phase, saturated salt solution
Washing.It is dry that anhydrous sodium sulfate 30.00 is added into organic phase, 1h is filtered.Filtrate is concentrated to dryness to obtain under the conditions of 30 DEG C
To crude product, crude product is mixed with ethyl acetate and hexane solution, 1h is beaten under the conditions of 30 DEG C, filtering is highly finished product 20.50g.
Embodiment two:
Compound (1) 9.76g (0.044mol) and compound (2) 15.00g (0.0486mol) are dissolved in methylene chloride
In 300ml, nitrogen protection.- 10 DEG C are cooled under stirring condition, potassium tert-butoxide 6.00g is inwardly added, temperature control -10~-5 DEG C are anti-
Answer 3h.Water is slowly added dropwise after fully reacting under the conditions of 0 DEG C, is stood after stirring 1h, liquid separation liquid separation takes organic phase, saturated salt solution
Washing.It is dry that anhydrous sodium sulfate 30.00 is added into organic phase, 2h is filtered.Filtrate is concentrated to dryness to obtain under the conditions of 30 DEG C
To crude product, crude product is mixed with ethyl acetate and hexane solution, is beaten 2h under the conditions of 40 DEG C, filtered up to highly finished product
22.43g。
Embodiment three:
Compound (1) 11.93g (0.0534mol) and compound (2) 15.00g (0.0486mol) are dissolved in methylene chloride
In 300ml, nitrogen protection.- 20 DEG C are cooled under stirring condition, potassium tert-butoxide 6.00g is inwardly added, temperature control -10~-5 DEG C are anti-
Answer 3h.Water is slowly added dropwise after fully reacting under the conditions of 0 DEG C, is stood after stirring 1h, liquid separation liquid separation takes organic phase, saturated salt solution
Washing.It is dry that anhydrous sodium sulfate 30.00 is added into organic phase, 3h is filtered.Filtrate is concentrated to dryness to obtain under the conditions of 30 DEG C
To crude product, crude product is mixed with ethyl acetate and hexane solution, is beaten 3h under the conditions of 50 DEG C, filtered up to highly finished product
21.47g。
Example IV:
By embodiment one, embodiment two, three resulting product of embodiment respectively as in tri- reaction flasks of A, B, C, in every
Methylene chloride 300ml is separately added into a reaction flask, 10% aqueous sodium carbonate adjusts stirring 1h, is adjusted with 10% hydrochloric acid
PH to 3, flow back 1h.20 DEG C are cooled to, liquid separation is washed.For being rotated under 25 DEG C of water bath conditions after anhydrous sodium sulfate 30.00 is dry
It is evaporated to dryness, is mixed with glacial acetic acid 100ml, hydrogen peroxide 9ml is added and reacts 9h under the conditions of 85 DEG C, is cooled to room after reaction
Temperature, the sodium hydroxide of 10% mass concentration of reaction solution adjust pH to 8~9, ethyl acetate washing, and water phase is adjusted with 10% hydrochloric acid
PH to 1~2, ethyl acetate extraction, washed organic layer are beaten after anhydrous sodium sulfate 30.00g is dry to interior addition n-hexane, mistake
Filter, is drying to obtain dexketoprofen, respectively obtains product 9.66g, 10.57g, 10.11g, code name is followed successively by A, B, C.
Embodiment five:
According to the method that 101928214 B of patent document CN is provided, compound (1) 22.00g, ethyl chloroacetate are taken
12.03g is dissolved in 50ml ethyl alcohol, stirs the lower ethanol solution (ethyl alcohol 50ml, sodium ethoxide 7.51g) that sodium ethoxide is added dropwise, is added dropwise
Flow back 3h, is cooled to 25 DEG C, and 30% sodium hydroxide solution 50ml is added, and stirs 2h, with salt acid for adjusting pH to 2, drops after the 2h that flows back
To 25 DEG C.Ethyl acetate 40ml extraction is added, is washed to neutrality, ethyl acetate is recovered under reduced pressure, glacial acetic acid 5ml is added,
15 1.02g of Amberlyst, hydrogen peroxide 20ml, 90 DEG C of reaction 10h are cooled to room temperature after reaction, are filtered, and filtrate is used
20% sodium hydroxide adjusts pH to the extraction of 9~10,20ml ethyl acetate, water phase, 6mol salt acid for adjusting pH to 1~2,25ml acetic acid
Ethyl ester extraction, is washed to neutrality, and anhydrous sodium sulfate dries, filters, and 5ml petroleum ether recrystallization, filtering, filtration cakes torrefaction is added in filtrate
White crystalline powder 18.01g is obtained, white solid 6.84g, number D are obtained after being split with dextrose octylame.
According to the method that patent document CN 16631772A is provided, compound (3) 8.80g is taken, dioxane 20ml is dissolved in,
60% nitric acid 20ml is added, reacts at room temperature 10h, after reaction, is extracted with 50ml ethyl acetate, anhydrous sodium sulfate is dry, mistake
The white solid 7.62g of 50ml petroleum ether recrystallization is added in filter, and white solid 2.97g, number E are obtained after being split with dextrose octylame.
The dexketoprofen product purity and yield that example IV and embodiment five are prepared, see the table below:
| A | B | C | D | E | |
| Yield | 78.2% | 85.6% | 81.9% | 60.1% | 65.6% |
| E.e.% | 98% | 98% | 98% | 92% | 90% |
From the above data, dextrorotation ketone Lip river is further synthesized to by the dexketoprofen intermediate that the present invention is prepared
Sweet smell, available higher yield and purity.
Claims (3)
1. a kind of synthetic method of dexketoprofen intermediate, it is characterised in that use following route:
Compound (1) is 3- acetyl Benzophenone, and compound (2) is monoxone 5- methyl-2- (1- methyl-1-phenyl-ethyl group)-ring
Hexyl ester, dexketoprofen intermediate are 3- (3- benzoy phenyl) -2S, 3R- dimethyl-oxirane -2- carboxyl -5-
Methyl-2- (1- methyl-1-phenyl-ethyl group)-hexamethylene alkyl ester.
2. the synthetic method of dexketoprofen intermediate according to claim 1, it is characterised in that the following steps are included: will change
It closes object (1), compound (2) is mixed with methylene chloride, and stirring cooling is added potassium tert-butoxide, reacts under the conditions of -20 DEG C~0 DEG C；
Water is slowly added dropwise after fully reacting, divides and takes organic phase, saturated common salt water washing is dry to organic anhydrous sodium sulfate that is added to, and takes out
Filter, filtrate decompression concentration, obtains product, and with ethyl alcohol, acetone soln mixing, mashing is filtered to obtain the final product.
3. the synthetic method of dexketoprofen intermediate according to claim 1, it is characterised in that reacting molar ratio is
Compound (1): compound (2)=0.8~1.1:1, preferably 0.9:1.
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| CN201810991647.3A CN109096229A (en) | 2018-08-29 | 2018-08-29 | A kind of synthetic method of dexketoprofen intermediate |
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| CN201810991647.3A CN109096229A (en) | 2018-08-29 | 2018-08-29 | A kind of synthetic method of dexketoprofen intermediate |
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| CN109096229A true CN109096229A (en) | 2018-12-28 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1490297A (en) * | 2002-10-15 | 2004-04-21 | 徐州瑞赛科技实业有限公司 | Preparation of dextroilbuprofen |
| CN101928214A (en) * | 2009-06-19 | 2010-12-29 | 黄石世星药业有限责任公司 | A kind of synthetic method of dexketoprofen tromethamine |
| CN102010327A (en) * | 2009-09-07 | 2011-04-13 | 浙江九洲药业股份有限公司 | Splitting method of (+/-)-2-(3-benzoyl)-phenylpropionic acid |
| JP2011219398A (en) * | 2010-04-07 | 2011-11-04 | Mitsui Chemicals Agro Inc | Method for producing branched aliphatic aldehyde |
| CN106631772A (en) * | 2016-12-14 | 2017-05-10 | 安徽省诚联医药科技有限公司 | Ketoprofen preparation method |
| CN106748718A (en) * | 2016-12-07 | 2017-05-31 | 江苏工程职业技术学院 | A kind of preparation technology of Ketoprofen |
-
2018
- 2018-08-29 CN CN201810991647.3A patent/CN109096229A/en active Pending
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|---|---|---|---|---|
| CN1490297A (en) * | 2002-10-15 | 2004-04-21 | 徐州瑞赛科技实业有限公司 | Preparation of dextroilbuprofen |
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| CN102010327A (en) * | 2009-09-07 | 2011-04-13 | 浙江九洲药业股份有限公司 | Splitting method of (+/-)-2-(3-benzoyl)-phenylpropionic acid |
| JP2011219398A (en) * | 2010-04-07 | 2011-11-04 | Mitsui Chemicals Agro Inc | Method for producing branched aliphatic aldehyde |
| CN106748718A (en) * | 2016-12-07 | 2017-05-31 | 江苏工程职业技术学院 | A kind of preparation technology of Ketoprofen |
| CN106631772A (en) * | 2016-12-14 | 2017-05-10 | 安徽省诚联医药科技有限公司 | Ketoprofen preparation method |
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| Title |
|---|
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