CN101747342A - 一种阿扑西林的合成工艺 - Google Patents
一种阿扑西林的合成工艺 Download PDFInfo
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- CN101747342A CN101747342A CN200810243075A CN200810243075A CN101747342A CN 101747342 A CN101747342 A CN 101747342A CN 200810243075 A CN200810243075 A CN 200810243075A CN 200810243075 A CN200810243075 A CN 200810243075A CN 101747342 A CN101747342 A CN 101747342A
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- amino
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- aspoxicillin
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- BHELIUBJHYAEDK-OAIUPTLZSA-N Aspoxicillin Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3[C@H](C(C)(C)S[C@@H]32)C(O)=O)=O)NC(=O)[C@H](N)CC(=O)NC)=CC=C(O)C=C1 BHELIUBJHYAEDK-OAIUPTLZSA-N 0.000 title claims abstract description 25
- 229960000202 aspoxicillin Drugs 0.000 title claims abstract description 25
- 238000005516 engineering process Methods 0.000 title abstract description 7
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- 239000002994 raw material Substances 0.000 claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 238000003756 stirring Methods 0.000 claims description 30
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 235000019260 propionic acid Nutrition 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 12
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 239000012043 crude product Substances 0.000 claims description 6
- 239000012065 filter cake Substances 0.000 claims description 6
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- 238000010792 warming Methods 0.000 claims description 5
- 150000008065 acid anhydrides Chemical class 0.000 claims description 4
- 239000005457 ice water Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 3
- QIOZLISABUUKJY-UHFFFAOYSA-N Thiobenzamide Chemical compound NC(=S)C1=CC=CC=C1 QIOZLISABUUKJY-UHFFFAOYSA-N 0.000 claims description 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000007791 liquid phase Substances 0.000 claims description 3
- HOGDNTQCSIKEEV-UHFFFAOYSA-N n'-hydroxybutanediamide Chemical compound NC(=O)CCC(=O)NO HOGDNTQCSIKEEV-UHFFFAOYSA-N 0.000 claims description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 238000007670 refining Methods 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000006386 neutralization reaction Methods 0.000 claims description 2
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 abstract 1
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 abstract 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 150000004684 trihydrates Chemical class 0.000 description 2
- 239000002253 acid Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Description
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200810243075 CN101747342B (zh) | 2008-12-08 | 2008-12-08 | 一种阿扑西林的合成工艺 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200810243075 CN101747342B (zh) | 2008-12-08 | 2008-12-08 | 一种阿扑西林的合成工艺 |
Publications (2)
Publication Number | Publication Date |
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CN101747342A true CN101747342A (zh) | 2010-06-23 |
CN101747342B CN101747342B (zh) | 2013-03-06 |
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CN 200810243075 Active CN101747342B (zh) | 2008-12-08 | 2008-12-08 | 一种阿扑西林的合成工艺 |
Country Status (1)
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CN (1) | CN101747342B (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102408437A (zh) * | 2011-10-21 | 2012-04-11 | 西南交通大学 | 一种阿扑西林的制备方法 |
CN103159783A (zh) * | 2013-03-06 | 2013-06-19 | 上海龙翔生物医药开发有限公司 | 一种阿扑西林三水酸的精制方法 |
CN103232475A (zh) * | 2013-04-16 | 2013-08-07 | 浙江普洛得邦制药有限公司 | 一种阿扑西林三水合物的制备方法 |
CN103333180A (zh) * | 2013-07-05 | 2013-10-02 | 湖南三清药业有限公司 | 一种阿扑西林的制备方法 |
CN103467492A (zh) * | 2013-08-14 | 2013-12-25 | 湖南三清药业有限公司 | 一种阿扑西林化合物,其药物组合物、制剂及制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4053609A (en) * | 1975-09-12 | 1977-10-11 | Tanabe Seiyaku Co., Ltd. | Penicillins and processes for preparing the same |
WO1999010324A1 (en) * | 1997-08-29 | 1999-03-04 | Naeja Pharmaceutical Inc. | AZETIDINONE DERIVATIVES AS β-LACTAMASE INHIBITORS |
-
2008
- 2008-12-08 CN CN 200810243075 patent/CN101747342B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4053609A (en) * | 1975-09-12 | 1977-10-11 | Tanabe Seiyaku Co., Ltd. | Penicillins and processes for preparing the same |
WO1999010324A1 (en) * | 1997-08-29 | 1999-03-04 | Naeja Pharmaceutical Inc. | AZETIDINONE DERIVATIVES AS β-LACTAMASE INHIBITORS |
Non-Patent Citations (1)
Title |
---|
陈芬儿: "《有机药物合成法》", 30 April 1999 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102408437A (zh) * | 2011-10-21 | 2012-04-11 | 西南交通大学 | 一种阿扑西林的制备方法 |
CN103159783A (zh) * | 2013-03-06 | 2013-06-19 | 上海龙翔生物医药开发有限公司 | 一种阿扑西林三水酸的精制方法 |
CN103159783B (zh) * | 2013-03-06 | 2016-04-27 | 上海龙翔生物医药开发有限公司 | 一种阿扑西林三水酸的精制方法 |
CN103232475A (zh) * | 2013-04-16 | 2013-08-07 | 浙江普洛得邦制药有限公司 | 一种阿扑西林三水合物的制备方法 |
CN103232475B (zh) * | 2013-04-16 | 2015-09-30 | 浙江普洛得邦制药有限公司 | 一种阿扑西林三水合物的制备方法 |
CN103333180A (zh) * | 2013-07-05 | 2013-10-02 | 湖南三清药业有限公司 | 一种阿扑西林的制备方法 |
CN103333180B (zh) * | 2013-07-05 | 2014-10-15 | 湖南三清药业有限公司 | 一种阿扑西林的制备方法 |
CN103467492A (zh) * | 2013-08-14 | 2013-12-25 | 湖南三清药业有限公司 | 一种阿扑西林化合物,其药物组合物、制剂及制备方法 |
CN103467492B (zh) * | 2013-08-14 | 2014-09-10 | 湖南三清药业有限公司 | 一种阿扑西林化合物,其药物组合物、制剂及制备方法 |
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Publication number | Publication date |
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CN101747342B (zh) | 2013-03-06 |
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Addressee: Zou Qiaogen Document name: Notification of Publication of the Application for Invention |
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DD01 | Delivery of document by public notice |
Addressee: Zou Qiaogen Document name: Notification of Patent Invention Entering into Substantive Examination Stage |
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C53 | Correction of patent of invention or patent application | ||
CB02 | Change of applicant information |
Address after: Nanjing Tech University Applicant after: Zou Qiaogen Address before: Central Road, Xuanwu District of Nanjing in Jiangsu province 210009 xinliji No. 258-27 building room 2305 Applicant before: Zou Qiaogen |
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EE01 | Entry into force of recordation of patent licensing contract |
Assignee: NANJING HEALTHNICE MEDICAL TECHNOLOGY Co.,Ltd. Assignor: Zou Qiaogen Contract record no.: 2012320000065 Denomination of invention: Technology for synthesizing aspoxicillin License type: Exclusive License Open date: 20100623 Record date: 20120209 |
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ASS | Succession or assignment of patent right |
Owner name: NANJING HEALTHNICE MEDICAL TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: ZOU QIAOGEN Effective date: 20121011 |
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C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20121011 Address after: 15, building 210009, A building, 5 new model road, Gulou District, Nanjing, Jiangsu Applicant after: NANJING HEALTHNICE MEDICAL TECHNOLOGY Co.,Ltd. Address before: Nanjing Tech University Applicant before: Zou Qiaogen |
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C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: 210009, A15 building, 5 new model road, Jiangsu, Nanjing Patentee after: NANJING HEALTHNICE PHARMACEUTICAL TECHNOLOGY CO.,LTD. Address before: 15, building 210009, A building, 5 new model road, Gulou District, Nanjing, Jiangsu Patentee before: NANJING HEALTHNICE MEDICAL TECHNOLOGY Co.,Ltd. |
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TR01 | Transfer of patent right | ||
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Effective date of registration: 20180511 Address after: 210009 A15 building, science and technology innovation building, 5 new model road, Nanjing, Jiangsu. Co-patentee after: NANJING HEALTHNICE PHARMACEUTICAL CO.,LTD. Patentee after: NANJING HEALTHNICE PHARMACEUTICAL TECHNOLOGY CO.,LTD. Address before: 210009 A15 building, science and technology innovation building, 5 new model road, Nanjing, Jiangsu. Patentee before: NANJING HEALTHNICE PHARMACEUTICAL TECHNOLOGY CO.,LTD. |
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TR01 | Transfer of patent right |
Effective date of registration: 20190529 Address after: 210009 15 Floor, No. 5 New Model Road, Gulou District, Nanjing City, Jiangsu Province Co-patentee after: NANJING HEALTHNICE PHARMACEUTICAL CO.,LTD. Patentee after: NANJING HEALTHNICE PHARMACEUTICAL TECHNOLOGY CO.,LTD. Co-patentee after: NANJING YINUO MEDICINE TECHNOLOGY Co.,Ltd. Address before: 210009 A15 building, science and technology innovation building, 5 new model road, Nanjing, Jiangsu. Co-patentee before: NANJING HEALTHNICE PHARMACEUTICAL CO.,LTD. Patentee before: NANJING HEALTHNICE PHARMACEUTICAL TECHNOLOGY CO.,LTD. |
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TR01 | Transfer of patent right |