CN1097583C - 制备氟苯尼考的中间体的方法 - Google Patents
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- AYIRNRDRBQJXIF-NXEZZACHSA-N (-)-Florfenicol Chemical compound CS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CF)NC(=O)C(Cl)Cl)C=C1 AYIRNRDRBQJXIF-NXEZZACHSA-N 0.000 title abstract description 8
- 229960003760 florfenicol Drugs 0.000 title abstract description 8
- 239000000543 intermediate Substances 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000002904 solvent Substances 0.000 description 12
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000006184 cosolvent Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical class ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- -1 oxazoline compound Chemical class 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- GKCXXDSWWDWUHS-BYPYZUCNSA-N ethyl (2s)-2-amino-3-hydroxypropanoate Chemical compound CCOC(=O)[C@@H](N)CO GKCXXDSWWDWUHS-BYPYZUCNSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/28—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及制备式I化合物的方法，其中R和R”的意义如文中所述。式I的化合物可用作制备氟苯尼考的中间体。
Description
发明领域
本发明涉及氟苯尼考的中间体及其新的制备方法。
发明背景
氟苯尼考{也称为[R-(R*，S*)]-2，2-二氯-N-[1-(氟甲基)-2-羟基-2-[4-(甲磺酰基)苯基]乙基]乙酰胺}是一种广谱抗菌剂，可用于治疗美国专利4361557(此中通过引用并入本文)中公开的革兰氏阳性、革兰氏阴性和立克次体引起的感染。本发明涉及氟苯尼考的中间体及其新的制备方法。正如可见于例如美国专利4876352(此中通过引用并入本文)中的那样，本说明书中所述的中间体可用于制备氟苯尼考。
简述
在一个实施方案中，本发明涉及制备式I化合物的方法：式中R是H、NO2、CH3S、CH3SO2或C4-C6烷基；R”是芳基、卤代芳基、苄基、取代苄基、C1-C6烷基、C3-C7环烷基以及卤代烷基，并且噁唑啉环的构型是4R反式：该方法包括a)使式II的化合物：
式中R如上所述，并且R’为H、C1-C6烷基、C3-C7环烷基、苄基、取代苄基或芳基；与一种还原剂诸如硼氢化钾在一适合的反应容器中接触得到式III的化合物：
式中R如上所述，并b)然后在相同的反应容器中，使式III的化合物与式IV的化合物：
R”-C≡N IV式中R”如上所述，反应以便获得式I的化合物。
本发明方法的优点在于它是制备氟苯尼考、其类似物和噁唑啉中间体的高效及经济的方法。
实施方案的详细说明
除非另外指明，本说明书和权利要求书使用的下列术语定义如下：
术语“质子溶剂”是指氢键键合溶剂，正如James B.Hendrickson，Cram，Donald J.和Hammond，George S.在Organic Chemistry，McgrawHill Book Company(New York，(1970)，第1279页)中所定义的溶剂。所述溶剂最好(但不必要)能将噁唑啉(I)从溶液中沉淀出来。这种溶剂包括(但不限于)水，C1-C10链烷酸诸如甲酸、乙酸等，C1-C10醇诸如甲醇和乙醇及其混合物，C2-C10二元醇诸如乙二醇和C1-C10三元醇诸如丙三醇。或者，为了使式I的噁唑啉化合物沉淀，可将质子溶剂和任何适合的共溶剂混合。这种共溶剂包括能与所述质子溶剂混溶的其他质子溶剂诸如C4-C10链烷烃，芳香溶剂诸如苯、甲苯、二甲苯，卤代苯诸如氯苯，和醚诸如二乙醚、叔丁基甲基醚、异丙基醚和四氢呋喃或任何上面溶剂或共溶剂的混合物。
术语“烷基”是指直链或支链烷基诸如甲基、乙基、丙基或仲丁基。或者，可具体指明烷基中的碳数。例如，C1-C6烷基指含1至6个碳原子的如上所述的烷基。“卤代烷基”是指一个或多个氢被卤素取代的上述的“烷基”。
术语“芳基”是指苯基或被C1-C6烷基或卤素取代的苯基。
取代苄基是指被C1-C6烷基或卤素取代的苄基。
术语“卤素”是指氟、氯、溴或碘。
术语“卤代芳基”是指被卤素取代的苯基。
在本说明书中，
上式为一种氨基二醇砜，被称为ADS。
制备本发明化合物的步骤由下面所示：
化学流程图
式中R、R’、R”的意义同上。
根据上面的化学流程图，式I的化合物可如下制备。将式II的化合物式中R和R’的意义同上，在约0-30℃的温度(优选室温)下、在一种质子溶剂诸如乙醇、乙二醇或更优选的甲醇中，用一种还原剂诸如NaBH4、Ca(BH4)2、LiBH4或更优选的KBH4处理约2-约8小时(更优选约4小时)，获得式III的化合物：
式中R的意义同上。
如果例如在上面所述的反应中，将甲醇用作还原反应的溶剂，那么可通过蒸馏回收供随后的反应再使用。除去甲醇也可提高式I化合物的收率。
在同一反应容器中，使式III的化合物与式IV的化合物接触
R”-C≡N IV式中R”的意义同上，式IV化合物的量与式III化合物相比为约1.1-约2.5当量，优选为约1.7当量。
式IV的化合物可以是例如苄腈或二氯乙腈。该反应根据所用腈和溶剂的不同可以在25℃至115℃之间进行。该反应进行约6到约30小时，优选18小时。然后冷却该反应混合物，例如通过加入冷水，并通过常规方法诸如过滤和洗涤处理而得到式I的化合物。最好该反应步骤在约6到约7的pH下进行。
本发明方法的一项优点是消除了分离ADS的需要，因为两个反应步骤在同一容器中进行。
优选形成二氯甲基噁唑啉，最优选形成苯基噁唑啉。
如下所示的丝氨酸乙酯是优选的式II的原料：
下面实施例以可实践的方式说明了本发明，但是这并不意味着对本发明范围的限制。
实施例1
将KBH4(1g)置于约40mL甲醇中。在搅拌下加入D-苏对-甲基磺酰苯基丝氨酸乙基酯(5g)。还原为ADS的反应用几小时完成并可通过HPLC监测。当反应完成后，加入20mL甘油用以破坏过量还原剂，并且通过蒸馏去除甲醇。除去甲醇后，将产生的混合物加热到105℃，加入苄腈(3.1mL)，同时继续加热约18小时。所需的噁唑啉的形成可通过HPLC监测。将反应物冷却到室温，并进行下列处理：加入冷水、过滤产生的固体物、用甲醇洗涤固体物、然后在真空下干燥。与苯基噁唑啉真实样品一致的物质的产量为约4.7g(81％)。
实施例2
将KBH4(1g)置于约40mL甲醇中。在搅拌下加入D-苏对-甲基磺酰苯基丝氨酸乙基酯(5g)。还原为ADS的反应用几小时完成并可通过HPLC监测。当反应完成时，加入20mL甘油用以破坏过量还原剂并且通过蒸馏去除甲醇。除去甲醇后，将产生的混合物用硫酸酸化到约6到7的pH，并加入二氯乙腈(2.4g)。在50℃下搅拌反应物约18小时。所需的噁唑啉的形成可通过HPLC监测。将反应物冷却到室温并进行下列处理：过滤固体物、用异丙醇和2％NaHCO3洗涤固体物、然后在真空下干燥。与二氯噁唑啉真实样品一致的物质的产量为约3.8g(65％)。
原料
式(II)和(IV)的原料是本领域技术人员熟知的。
Claims (4)
1.制备式I化合物的方法：
式中R是H、NO2、CH3S、CH3SO2或C4-C6烷基；R”是芳基、卤代芳基、苄基、取代苄基、C1-C6烷基、C3-C7环烷基以及卤代烷基，并且噁唑啉环的构型是4R反式；该方法包括a)使式II的化合物：式中R如上所述，并且R’为H、C1-C6烷基、C3-C7环烷基、苄基、取代苄基或芳基；与一种还原剂在适合的反应容器接触以便获得式III的化合物：
式中R如上所述，和b)然后在相同的反应容器中，使式III的化合物与式IV的化合物：
R”-C≡N IV反应以便获得式I的化合物。
2.按照权利要求1的方法，其中所述还原剂是硼氢化钾。
3.按照权利要求1的方法，其中被形成的式I化合物是：
4.按照权利要求1的方法，其中被形成的式I化合物是：
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/699,271 US5663361A (en) | 1996-08-19 | 1996-08-19 | Process for preparing intermediates to florfenicol |
| US08/699,271 | 1996-08-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1233244A CN1233244A (zh) | 1999-10-27 |
| CN1097583C true CN1097583C (zh) | 2003-01-01 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97198768A Expired - Lifetime CN1097583C (zh) | 1996-08-19 | 1997-08-18 | 制备氟苯尼考的中间体的方法 |
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| Country | Link |
|---|---|
| US (1) | US5663361A (zh) |
| EP (1) | EP0922040B2 (zh) |
| JP (1) | JP3274868B2 (zh) |
| KR (1) | KR100286851B1 (zh) |
| CN (1) | CN1097583C (zh) |
| AR (1) | AR008298A1 (zh) |
| AT (1) | ATE283847T1 (zh) |
| AU (1) | AU714495B2 (zh) |
| BR (1) | BR9711318B1 (zh) |
| CA (1) | CA2264116C (zh) |
| CO (1) | CO4560550A1 (zh) |
| CZ (1) | CZ297915B6 (zh) |
| DE (1) | DE69731835T3 (zh) |
| DK (1) | DK0922040T3 (zh) |
| ES (1) | ES2234026T5 (zh) |
| HK (1) | HK1017890A1 (zh) |
| HU (1) | HU229610B1 (zh) |
| ID (1) | ID18047A (zh) |
| IL (1) | IL128574A (zh) |
| MY (1) | MY115679A (zh) |
| NO (1) | NO312962B1 (zh) |
| NZ (1) | NZ334111A (zh) |
| PE (1) | PE99798A1 (zh) |
| PL (2) | PL198553B1 (zh) |
| PT (1) | PT922040E (zh) |
| SI (1) | SI0922040T1 (zh) |
| SK (1) | SK286124B6 (zh) |
| TR (2) | TR200800474T2 (zh) |
| TW (1) | TW381075B (zh) |
| WO (1) | WO1998007709A1 (zh) |
| ZA (1) | ZA977406B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106278964A (zh) * | 2016-07-31 | 2017-01-04 | 浙江润康药业有限公司 | 氟苯尼考的制备方法 |
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| MXPA04008677A (es) * | 2002-03-08 | 2004-12-06 | Schering Plough Ltd | Antibioticos novedosos del tipo florfenicol. |
| CL2004001293A1 (es) | 2003-05-29 | 2005-05-06 | Schering Plough Ltd | Composicion farmaceutica que comprende compuestos antibacterianos como florfenicol, tiamfenicol, cloramfenicol en combinacion con al menos un portador seleccionado de triacetina, dimetilacetamida o una mezcla de ellas; y su uso en el tratamiento de u |
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| US20050049210A1 (en) * | 2003-08-27 | 2005-03-03 | Idexx Laboratories, Inc. | Methods for the controlled delivery of pharmacologically active compounds |
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| MX2007006072A (es) * | 2004-11-19 | 2007-07-11 | Schering Plough Ltd | Control de parasitos en animales mediante el uso de derivados del parasiticida 2-fenil-3-(1h-pirrol-2-il)acrilonitrilo. |
| MX2007007528A (es) * | 2004-12-21 | 2007-10-08 | Intervet Int Bv | Composicion veterinaria inyectable. |
| AR054380A1 (es) * | 2005-06-09 | 2007-06-20 | Schering Plough Ltd | Control de parasitos en animales con derivados de n- ((feniloxi) fenil) -1,1,1-trifluorometansulfonamida y de n-(fenilsulfanil) fenil) -1,1,1-trifluorometansulfonamida |
| MX2008003187A (es) * | 2005-09-07 | 2008-03-18 | Schering Plough Ltd | Un procedimiento mejorado para preparar compuestos de aminodiol protegidos con oxazodilina, utiles como intermediarios para el florfenicol. |
| US8119667B2 (en) * | 2005-12-29 | 2012-02-21 | Schering-Plough Animal Health Corporation | Carbonates of fenicol antibiotics |
| US7518017B2 (en) | 2006-02-17 | 2009-04-14 | Idexx Laboratories | Fenicol compounds and methods synthesizing 2-trifluoroacetamido-3-substituted propiophenone compounds |
| US20070238700A1 (en) * | 2006-04-10 | 2007-10-11 | Winzenberg Kevin N | N-phenyl-1,1,1-trifluoromethanesulfonamide hydrazone derivative compounds and their usage in controlling parasites |
| US8044230B2 (en) * | 2006-12-13 | 2011-10-25 | Intervet Inc. | Water-soluble prodrugs of chloramphenicol, thiamphenicol, and analogs thereof |
| WO2008076259A1 (en) * | 2006-12-13 | 2008-06-26 | Schering-Plough Ltd. | Water-soluble prodrugs of florfenicol and its analogs |
| MX2009011642A (es) * | 2007-04-27 | 2010-01-29 | Schering Plough Ltd | Compuestos y metodos para potenciar la solubilidad de florfenicol y antibioticos estructuralmente relacionados utilizando ciclodextrinas. |
| PE20090758A1 (es) * | 2007-05-30 | 2009-06-24 | Schering Plough Ltd | Un proceso para la preparacion de compuestos de aminodiol protegidos con oxazolina, utiles como intermediarios para florfenicol |
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| ES2666187T3 (es) | 2007-06-27 | 2018-05-03 | E. I. Du Pont De Nemours And Company | Procedimiento de control de plagas en animales |
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| US7550625B2 (en) * | 2007-10-19 | 2009-06-23 | Idexx Laboratories | Esters of florfenicol |
| KR20100085162A (ko) * | 2007-11-09 | 2010-07-28 | 인터벳 인터내셔널 비.브이. | 속방성 고체 제형, 제조 및 이의 용도 |
| TWI468407B (zh) | 2008-02-06 | 2015-01-11 | Du Pont | 中離子農藥 |
| EP2321269B1 (en) * | 2008-07-30 | 2018-09-19 | Intervet International B.V. | Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol |
| UA107804C2 (en) | 2009-08-05 | 2015-02-25 | Du Pont | Mixtures of pesticides mezoionnyh |
| BR112012002519A2 (pt) | 2009-08-05 | 2019-09-24 | Du Pont | "pesticidas mesoiônicos" |
| UA110924C2 (uk) | 2009-08-05 | 2016-03-10 | Е. І. Дю Пон Де Немур Енд Компані | Мезоіонні пестициди |
| KR20120047996A (ko) | 2009-08-05 | 2012-05-14 | 이 아이 듀폰 디 네모아 앤드 캄파니 | 메소이온성 살충제 |
| BRPI1002023A2 (pt) | 2010-03-01 | 2011-10-25 | Nanocore Biotecnologia S A | forma farmacêutica sólida de dissolução rápida para tratamento de infecções bacterianas |
| JP5933530B2 (ja) | 2010-05-27 | 2016-06-08 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニーＥ．Ｉ．Ｄｕ Ｐｏｎｔ Ｄｅ Ｎｅｍｏｕｒｓ Ａｎｄ Ｃｏｍｐａｎｙ | ４−［５−［３−クロロ−５−（トリフルオロメチル）フェニル］−４，５−ジヒドロ−５−（トリフルオロメチル）−３−イソオキサゾリル］−ｎ−［２−オキソ−２−［（２，２，２−トリフルオロエチル）アミノ］エチル］−１−ナフタレンカルボキサミドの結晶質形態 |
| WO2012087630A1 (en) | 2010-12-20 | 2012-06-28 | E.I. Du Pont De Nemours And Company | Pyridine and pyrimidine compounds for controlling invertebrate |
| WO2013158422A1 (en) | 2012-04-17 | 2013-10-24 | E. I. Du Pont De Nemours And Company | Heterocyclic compounds for controlling invertebrate pests |
| CN102911133B (zh) * | 2012-10-31 | 2014-07-02 | 绍兴民生医药有限公司 | (4r,5r)-2-二氯甲基-4,5-二氢-5-(4-甲砜基苯基)-4-恶唑甲醇的纯化方法 |
| CN103254147B (zh) * | 2013-04-19 | 2016-04-06 | 浙江科技学院 | 一种d-苏式-2-(二氯甲基)-4,5-二氢-5-[对-（甲砜基）苯基]-4-噁唑甲醇的制备方法 |
| CN106631872A (zh) * | 2016-12-13 | 2017-05-10 | 浙江普洛家园药业有限公司 | 一种氟苯尼考类似物中间体的合成方法 |
| CN110272856B (zh) * | 2019-05-08 | 2022-05-03 | 江南大学 | 一种表达d-苏氨酸醛缩酶的重组菌及其构建方法与应用 |
| CN117466787B (zh) * | 2023-12-28 | 2024-03-22 | 山东国邦药业有限公司 | 一种氟苯尼考中间体的制备方法 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106278964A (zh) * | 2016-07-31 | 2017-01-04 | 浙江润康药业有限公司 | 氟苯尼考的制备方法 |
| CN106278964B (zh) * | 2016-07-31 | 2018-01-16 | 浙江润康药业有限公司 | 氟苯尼考的制备方法 |
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