CN101215242A - Technique for synthesizing aceclofenac benzyl ester - Google Patents
Technique for synthesizing aceclofenac benzyl ester Download PDFInfo
- Publication number
- CN101215242A CN101215242A CNA2007100192209A CN200710019220A CN101215242A CN 101215242 A CN101215242 A CN 101215242A CN A2007100192209 A CNA2007100192209 A CN A2007100192209A CN 200710019220 A CN200710019220 A CN 200710019220A CN 101215242 A CN101215242 A CN 101215242A
- Authority
- CN
- China
- Prior art keywords
- aceclofenac
- benzyl ester
- ethyl acetate
- diclofenac
- residue
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- RLKZSYGBKCIRFJ-UHFFFAOYSA-N (2-oxo-2-phenylmethoxyethyl) 2-[2-(2,6-dichloroanilino)phenyl]acetate Chemical compound ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1CC(=O)OCC(=O)OCC1=CC=CC=C1 RLKZSYGBKCIRFJ-UHFFFAOYSA-N 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 8
- 230000002194 synthesizing effect Effects 0.000 title 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 238000010025 steaming Methods 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 8
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229960001259 diclofenac Drugs 0.000 claims abstract description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims abstract description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 4
- 239000013078 crystal Substances 0.000 claims abstract description 4
- 238000001035 drying Methods 0.000 claims abstract description 4
- 239000007788 liquid Substances 0.000 claims abstract description 4
- PWCONBNHBCCZHP-UHFFFAOYSA-N benzyl acetate hydrobromide Chemical compound Br.CC(=O)OCC1=CC=CC=C1 PWCONBNHBCCZHP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000008030 elimination Effects 0.000 claims description 3
- 238000003379 elimination reaction Methods 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229960004420 aceclofenac Drugs 0.000 abstract description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 abstract 3
- 230000006837 decompression Effects 0.000 abstract 2
- 238000009991 scouring Methods 0.000 abstract 2
- 238000011049 filling Methods 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 230000002045 lasting effect Effects 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 230000000202 analgesic effect Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- MNIPYSSQXLZQLJ-UHFFFAOYSA-N Biofenac Chemical compound OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl MNIPYSSQXLZQLJ-UHFFFAOYSA-N 0.000 description 2
- -1 benzyl ester Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis technology of aceclofenac benzyloxy carbonyl. The synthesis technology of which is stated by the invention comprises filling diclofenac and DMF in a reaction bottle, stirring to dissolve, dripping bromoacetic acid benzyloxy carbonyl under the condition of constant temperature lasting for 30 minute, stirring to react for 8 hours when temperature increases to 50 DEG C, steaming out deepener through decompression, adding in acetic acid ethyl ester in residue, filtering to remove salt, scouring filter solution to divide oil layer, drying with anhydrous sodium sulfate, steaming out acetic acid ethyl ester through decompression, obtaining light green oily viscous liquid, scouring residues with cyclohexane for a second time, and then recrystallizing with methyl alcohol to obtain aceclofenac benzyloxy carbonyl with crystal (mp.67-69 DEG C).
Description
Technical field
The present invention relates to a kind of synthesis technique of aceclofenac benzyl ester.
Background technology
Aceclofenac is the anti-inflammatory analgesic that began to be used for clinical treatment in recent years, and because of its gastrointestinal side effect that stronger rare conventional anti-inflammatory analgesic of anti-inflammatory analgesic is arranged, clinical usage quantity rises day by day.
The synthesis technique that the purpose of this invention is to provide a kind of aceclofenac benzyl ester.Diclofenac and benzyl acetate bromide reaction are generated aceclofenac benzyl ester, under the catalysis of palladium carbon, slough the benzyl ester by hydrogenation and get Aceclofenac.
Summary of the invention
The invention provides a kind of synthesis technique of aceclofenac benzyl ester.
The synthesis technique of aceclofenac benzyl ester of the present invention is: drop into diclofenac and DMF in reaction flask, stirring makes dissolving, under room temperature condition, the dripping bromine jasmal, added in about 30 minutes, be warming up to 50 ℃ of stirring reactions 8 hours, the dark agent of pressure reducing and steaming, in residue, add ethyl acetate, cross the elimination sodium salt, filtrate water is washed, and divides oil-yielding stratum, anhydrous sodium sulfate drying, the pressure reducing and steaming ethyl acetate gets light green oily thick liquid, and this residue is washed secondary with hexanaphthene, use recrystallizing methanol then, get aceclofenac benzyl ester white crystals (mp.67-69 ℃).Feed ratio is diclofenac: DMF: benzyl acetate bromide: ethyl acetate (40-60g: 200-400ml: 30-60g: 200-600ml).
The aceclofenac benzyl ester steady quality of synthetic gained meets manufacturing requirements fully.
Embodiment
Further set forth the present invention below by example, but do not place restrictions on the present invention.
In reaction flask, drop into 50.5g (0.166mol) diclofenac and 300ml DMF, stirring makes dissolving, under room temperature condition, drip 45.1g (0.193mol) benzyl acetate bromide, added in about 30 minutes, be warming up to 50 ℃ of stirring reactions 8 hours, the dark agent of pressure reducing and steaming, add the 400ml ethyl acetate in residue, cross the elimination sodium salt, filtrate water is washed, divide oil-yielding stratum, anhydrous sodium sulfate drying, the pressure reducing and steaming ethyl acetate gets light green oily thick liquid, this residue is washed secondary with hexanaphthene, use recrystallizing methanol then, 43.5g aceclofenac benzyl ester white crystals (yield: 69%, mp.67-69 ℃).
Claims (2)
1. the synthesis technique of an aceclofenac benzyl ester, it is characterized in that in reaction flask, dropping into diclofenac and DMF, stirring makes dissolving, under room temperature condition, the dripping bromine jasmal added in about 30 minutes, be warming up to 50 ℃ of stirring reactions 8 hours, the dark agent of pressure reducing and steaming adds ethyl acetate in residue, cross the elimination sodium salt, filtrate water is washed, divide oil-yielding stratum, anhydrous sodium sulfate drying, pressure reducing and steaming ethyl acetate, get light green oily thick liquid, this residue is washed secondary with hexanaphthene, uses recrystallizing methanol then, gets aceclofenac benzyl ester white crystals (mp.67-69 ℃).
2. the synthesis technique of a kind of aceclofenac benzyl ester according to claim 1 is characterized in that under above-mentioned synthesis condition, and its feed ratio is diclofenac: DMF: benzyl acetate bromide: ethyl acetate (40-60g: 200-400ml: 30-60g: 200-600ml).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100192209A CN101215242A (en) | 2007-01-05 | 2007-01-05 | Technique for synthesizing aceclofenac benzyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100192209A CN101215242A (en) | 2007-01-05 | 2007-01-05 | Technique for synthesizing aceclofenac benzyl ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101215242A true CN101215242A (en) | 2008-07-09 |
Family
ID=39621762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100192209A Withdrawn CN101215242A (en) | 2007-01-05 | 2007-01-05 | Technique for synthesizing aceclofenac benzyl ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101215242A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102924313A (en) * | 2012-11-13 | 2013-02-13 | 江苏吉贝尔药业有限公司 | Novel preparation method of benzyl aceclofenac |
-
2007
- 2007-01-05 CN CNA2007100192209A patent/CN101215242A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102924313A (en) * | 2012-11-13 | 2013-02-13 | 江苏吉贝尔药业有限公司 | Novel preparation method of benzyl aceclofenac |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C04 | Withdrawal of patent application after publication (patent law 2001) | ||
| WW01 | Invention patent application withdrawn after publication |