CN101928214B - 右旋酮洛芬氨丁三醇的一种合成方法 - Google Patents
右旋酮洛芬氨丁三醇的一种合成方法 Download PDFInfo
- Publication number
- CN101928214B CN101928214B CN 200910062741 CN200910062741A CN101928214B CN 101928214 B CN101928214 B CN 101928214B CN 200910062741 CN200910062741 CN 200910062741 CN 200910062741 A CN200910062741 A CN 200910062741A CN 101928214 B CN101928214 B CN 101928214B
- Authority
- CN
- China
- Prior art keywords
- dexketoprofen
- cooled
- octylglucamine
- centrifugal
- purified water
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 21
- QUZMDHVOUNDEKW-MERQFXBCSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;(2s)-2-(3-benzoylphenyl)propanoic acid Chemical compound OCC(N)(CO)CO.OC(=O)[C@@H](C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 QUZMDHVOUNDEKW-MERQFXBCSA-N 0.000 title claims abstract description 19
- 229960005448 dexketoprofen trometamol Drugs 0.000 title claims abstract description 19
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- ZRRNJJURLBXWLL-REWJHTLYSA-N (2r,3r,4r,5s)-6-(octylamino)hexane-1,2,3,4,5-pentol Chemical compound CCCCCCCCNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO ZRRNJJURLBXWLL-REWJHTLYSA-N 0.000 claims abstract description 37
- DKYWVDODHFEZIM-NSHDSACASA-N dexketoprofen Chemical class OC(=O)[C@@H](C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-NSHDSACASA-N 0.000 claims abstract description 22
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960000281 trometamol Drugs 0.000 claims abstract description 10
- 239000013078 crystal Substances 0.000 claims abstract description 9
- 238000007670 refining Methods 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 75
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 49
- 239000008213 purified water Substances 0.000 claims description 43
- 239000012065 filter cake Substances 0.000 claims description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- 238000005406 washing Methods 0.000 claims description 33
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 32
- 229960002783 dexketoprofen Drugs 0.000 claims description 30
- 238000003756 stirring Methods 0.000 claims description 25
- 238000001035 drying Methods 0.000 claims description 21
- 239000012452 mother liquor Substances 0.000 claims description 20
- 239000000243 solution Substances 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 16
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 16
- 239000012085 test solution Substances 0.000 claims description 16
- 238000002425 crystallisation Methods 0.000 claims description 15
- 230000008025 crystallization Effects 0.000 claims description 15
- 238000010792 warming Methods 0.000 claims description 14
- 238000004821 distillation Methods 0.000 claims description 13
- -1 dexketoprofen N-Octylglucamine salt Chemical class 0.000 claims description 12
- 239000006210 lotion Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 238000011084 recovery Methods 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 9
- 235000021463 dry cake Nutrition 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 235000019441 ethanol Nutrition 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 4
- 238000005267 amalgamation Methods 0.000 claims description 4
- 235000012970 cakes Nutrition 0.000 claims description 4
- 238000005352 clarification Methods 0.000 claims description 4
- 239000002826 coolant Substances 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 229940002612 prodrug Drugs 0.000 abstract description 3
- 239000000651 prodrug Substances 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000012046 mixed solvent Substances 0.000 abstract description 2
- 230000006340 racemization Effects 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract 3
- 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 abstract 2
- 229960000991 ketoprofen Drugs 0.000 abstract 2
- 238000000926 separation method Methods 0.000 abstract 1
- 238000009833 condensation Methods 0.000 description 10
- 230000005494 condensation Effects 0.000 description 10
- 206010013786 Dry skin Diseases 0.000 description 7
- 239000012266 salt solution Substances 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 5
- 230000000202 analgesic effect Effects 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229940025084 amphetamine Drugs 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 206010024453 Ligament sprain Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200910062741 CN101928214B (zh) | 2009-06-19 | 2009-06-19 | 右旋酮洛芬氨丁三醇的一种合成方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200910062741 CN101928214B (zh) | 2009-06-19 | 2009-06-19 | 右旋酮洛芬氨丁三醇的一种合成方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101928214A CN101928214A (zh) | 2010-12-29 |
CN101928214B true CN101928214B (zh) | 2012-12-19 |
Family
ID=43367700
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 200910062741 Active CN101928214B (zh) | 2009-06-19 | 2009-06-19 | 右旋酮洛芬氨丁三醇的一种合成方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101928214B (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102850204B (zh) * | 2011-06-29 | 2015-08-19 | 徐州医学院 | 一种(s)-2-芳基丙酸类非甾体抗炎药的拆分方法 |
CN102381986A (zh) * | 2011-07-25 | 2012-03-21 | 南京特丰药业股份有限公司 | 一种右旋布洛芬氨丁三醇盐及其口服溶液的制备方法 |
CN102743341B (zh) * | 2012-07-28 | 2014-02-26 | 西安德天药业股份有限公司 | 右旋酮洛芬氨丁三醇缓释微粒及其制备方法和缓释制剂 |
CN109096229A (zh) * | 2018-08-29 | 2018-12-28 | 南京正科医药股份有限公司 | 一种右旋酮洛芬中间体的合成方法 |
CN115607509B (zh) * | 2022-10-11 | 2024-01-30 | 南京正科医药股份有限公司 | 一种右旋酮洛芬氨丁三醇注射液及其制备工艺 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5554789A (en) * | 1992-11-10 | 1996-09-10 | Laboratorios Menarini S.A. | Arylpropionic derivative, a process for the preparation and the use thereof as an analgesic agent |
US5808069A (en) * | 1993-03-09 | 1998-09-15 | Dompe' Farmaceutici Spa | Salts of 2-(3-benzoylphenyl) propionic acid with organic bases and pharmaceutical compositions thereof |
CN1349970A (zh) * | 2001-11-02 | 2002-05-22 | 中国科学院上海有机化学研究所 | 2-(3-苯甲酰基苯基)丙酸的对映体的制备方法 |
CN1418886A (zh) * | 2002-12-03 | 2003-05-21 | 中国人民解放军第四军医大学第一附属医院 | 右酮洛芬葡辛胺盐及制备方法和以该活性成分的药物组合物 |
-
2009
- 2009-06-19 CN CN 200910062741 patent/CN101928214B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5554789A (en) * | 1992-11-10 | 1996-09-10 | Laboratorios Menarini S.A. | Arylpropionic derivative, a process for the preparation and the use thereof as an analgesic agent |
US5808069A (en) * | 1993-03-09 | 1998-09-15 | Dompe' Farmaceutici Spa | Salts of 2-(3-benzoylphenyl) propionic acid with organic bases and pharmaceutical compositions thereof |
CN1349970A (zh) * | 2001-11-02 | 2002-05-22 | 中国科学院上海有机化学研究所 | 2-(3-苯甲酰基苯基)丙酸的对映体的制备方法 |
CN1418886A (zh) * | 2002-12-03 | 2003-05-21 | 中国人民解放军第四军医大学第一附属医院 | 右酮洛芬葡辛胺盐及制备方法和以该活性成分的药物组合物 |
Also Published As
Publication number | Publication date |
---|---|
CN101928214A (zh) | 2010-12-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101928214B (zh) | 右旋酮洛芬氨丁三醇的一种合成方法 | |
CN105236452B (zh) | 一种硝酸钠与氯化钾反应生产高纯硝酸钾的工艺 | |
CN106167449A (zh) | 一种对羟基苯乙酮的合成方法 | |
CN103420881B (zh) | 一种新的药用消旋羟蛋氨酸钙的制备方法 | |
CN105585454A (zh) | 受阻双酚型抗氧剂的制备方法 | |
CN106916138A (zh) | 一种甲烷二磺酸亚甲酯的合成方法 | |
CN110386867A (zh) | 一种乙基香兰素的连续化纯化方法 | |
CN100378055C (zh) | 酸和丙酮水溶液一步法制备酸性棉酚衍生物的方法 | |
CN103788112B (zh) | 一种苄基生物素脱苄制备生物素的方法 | |
CN103265443A (zh) | 一种工业生产高纯度亚氨基二乙酸的方法 | |
CN105541951A (zh) | 一种奥贝胆酸的精制方法 | |
CN103922925B (zh) | 一种非诺贝酸的生产工艺 | |
CN114933588A (zh) | 雷贝拉唑钠粗品的精制方法 | |
CN103421043A (zh) | 一种烷基酯法合成草甘膦水解工艺的改进方法 | |
CN106349144A (zh) | 一种(s)‑奥拉西坦中间体的制备方法 | |
CN107382752B (zh) | 一种回收制作d-生物素的原料右胺的方法 | |
CN101823986A (zh) | 一种肼基甲酸叔丁酯的制备方法 | |
CN114181078B (zh) | 一种3-羟基-2-萘甲酸苯酯的精制方法 | |
CN110483270B (zh) | 一种高效绿色合成非诺贝特酸的制备方法 | |
CN102746178A (zh) | 氟他胺的制备新方法 | |
CN220238535U (zh) | 一种氟啶胺甲醇母液精制*** | |
CN113861011A (zh) | 一种邻甲基苯乙酸生产工艺 | |
CN115322239B (zh) | 一种从双炔失碳酯母液物中回收双酮的方法 | |
CN114014756B (zh) | 一种3-羟基-2-萘甲酸苯酯的制备方法 | |
CN109704940B (zh) | 一种α-溴代肉桂醛的合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A Synthesis Method of D-Ketoprofen Aminobutanol Triol Effective date of registration: 20230421 Granted publication date: 20121219 Pledgee: Bank of China Limited Huangshi Branch Pledgor: HUANGSHI SHIXING PHARMACEUTICAL Co.,Ltd. Registration number: Y2023420000174 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20121219 Pledgee: Bank of China Limited Huangshi Branch Pledgor: HUANGSHI SHIXING PHARMACEUTICAL Co.,Ltd. Registration number: Y2023420000174 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A synthetic method of D-ketoprofen tromethamine Granted publication date: 20121219 Pledgee: Bank of China Limited Huangshi Branch Pledgor: HUANGSHI SHIXING PHARMACEUTICAL Co.,Ltd. Registration number: Y2024980013802 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |