CN110483389A - 一种氟尼辛的精制方法 - Google Patents

一种氟尼辛的精制方法 Download PDF

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Publication number
CN110483389A
CN110483389A CN201910883733.7A CN201910883733A CN110483389A CN 110483389 A CN110483389 A CN 110483389A CN 201910883733 A CN201910883733 A CN 201910883733A CN 110483389 A CN110483389 A CN 110483389A
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Prior art keywords
flunixin
refining methd
triethylamine
filter cake
centrifugation
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CN201910883733.7A
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Inventor
马居良
殷习栋
郑真真
李志远
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SHANDONG JIULONG HISINCE PHARMACEUTICAL Co Ltd
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SHANDONG JIULONG HISINCE PHARMACEUTICAL Co Ltd
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Priority to CN201910883733.7A priority Critical patent/CN110483389A/zh
Publication of CN110483389A publication Critical patent/CN110483389A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

本发明属于化学精制技术领域，具体涉及一种氟尼辛的精制方法。该方法包括下述的步骤：氟尼辛溶解于三乙胺和乙醇的混合溶剂中，向溶液中滴加入丙酮，降温至0‑5℃析晶，离心，干燥得氟尼辛精品。该方法采用三乙胺、乙醇和水对氟尼辛进行精制，乙醇可以回收套用，总收率可达93％。

Description

一种氟尼辛的精制方法
技术领域
本发明属于化学合成技术领域，具体涉及一种氟尼辛的精制方法。
背景技术
氟尼辛的化学式:C14H13F3N2，化学名为2-[[2-甲基-3-(三氟甲基)苯基]氨基]-3-吡啶甲酸，结构式：
氟尼辛是制备氟尼辛葡甲胺的关键原料，使用上主要制备成氟尼辛葡甲胺使用。氟尼辛葡甲胺(flunixin meglumine)是一种新型的、非甾体类动物专用的解热镇痛药物，属于烟酸类衍生物，是环氧化酶的抑制剂。由美国先灵葆雅公司于20世纪90年代开发(商品名为Banamine)，现已在美国、法国、瑞士、德国、英国等许多国家广泛应用。
目前文献中关于氟尼辛的精制方法有报道的比较少，通常采用的先后在水和乙醇或乙腈中打浆的方式精制。
发明内容
为了解决上述的技术问题，本发明提供一种氟尼辛的精制方法，其操作简单，反应时间短，催化剂可反复回收使用，收率高。
本发明是通过下述的技术方案来实现的：
一种的氟尼辛的精制方法，包括下述的步骤：
将氟尼辛粗品溶解于三乙胺和乙醇混合溶剂中，升温溶清，降温析晶，离心，滤饼溶解于水中，用盐酸调节pH＝5-6，析出固体，离心，干燥得成品。
上的氟尼辛的精制方法中，所述混合溶剂为三乙胺和乙醇，所述三乙胺与乙醇的重量比1:3，所述混合溶剂用量为氟尼辛粗品重量的3倍。
上的氟尼辛的精制方法中，所述溶清温度为75℃-80℃。
上的氟尼辛的精制方法中，所述析晶温度为5℃-10℃。
上的氟尼辛的精制方法中，所述析晶时间为1.5-2小时。
上的氟尼辛的精制方法中，所述滤饼溶解用水量为滤饼湿重的2.5-3倍。
上述的氟尼辛的精制方法，详细步骤为：将氟尼辛粗品加入到三乙胺和乙醇的混合溶剂中，搅拌，升温至溶解，控制温度至75℃-80℃，降温至5℃-10℃，析晶1.5-2h后，离心，滤饼和滤饼湿重2.5-3倍重量的水投入反应釜中，用盐酸调节pH＝5-6，离心，滤饼干燥得精制品。
与现有技术相比，本发明的有益效果如下：
(1)本发明的氟尼辛的精制方法，采用三乙胺、乙醇和水对氟尼辛进行精制，乙醇可以回收套用，总收率可达93％。
(2)本发明中氟尼辛的精制方法，生产周期短，乙醇三乙胺重结晶母液回收的同时，可以把重结晶损失的氟尼辛粗品回收后，多次精制，提高回收率，有效降低了生产成本。
具体实施方式
下面结合具体实施例对本发明作更进一步的说明，以便本领域的技术人员更了解本发明，但并不因此限制本发明。
实施例1
1000L反应釜中加入200kg氟尼辛粗品，分别投入600kg乙醇和200kg三乙胺，搅拌，升温至75℃-80℃，搅拌至完全溶解，降温至5℃-10℃后，搅拌1.5h，离心，滤饼加入到1000L反应釜中，加入滤饼湿重2.5倍重量的水，搅拌溶解，用浓盐酸调节pH＝5.5，离心，干燥得精制品186.4kg，收率93.2％。
实施例2
1000L反应釜中加入200kg氟尼辛粗品，分别投入600kg乙醇和200kg三乙胺，搅拌，升温至75℃-80℃，搅拌至完全溶解，降温至5℃-10℃后，搅拌2h，离心，滤饼加入到1000L反应釜中，加入滤饼湿重2.5倍重量的水，搅拌溶解，用浓盐酸调节pH＝5.3，离心，干燥得精制品187.6kg，收率93.8％。

Claims (7)

1.一种的氟尼辛的精制方法，包括下述的步骤：
将氟尼辛粗品溶解于三乙胺和乙醇混合溶剂中，升温溶清，降温析晶，离心，滤饼溶解于水中，用盐酸调节pH＝5-6，析出固体，离心，干燥得成品。
2.根据权利要求1所述的氟尼辛的精制方法，其特征在于，所述混合溶剂为三乙胺和乙醇，所述三乙胺与乙醇的重量比1:3，所述混合溶剂用量为氟尼辛粗品重量的3倍。
3.根据权利要求1所述的氟尼辛的精制方法，其特征在于，所述溶清温度为75℃-80℃。
4.根据权利要求1所述的氟尼辛的精制方法，其特征在于，所述析晶温度为5℃-10℃。
5.根据权利要求1所述的氟尼辛的精制方法，其特征在于，所述析晶时间为1.5-2小时。
6.根据权利要求1所述的氟尼辛的精制方法，其特征在于，所述滤饼溶解用水量为滤饼湿重的2.5-3倍。
7.根据权利要求1所述的氟尼辛的精制方法，其特征在于，详细步骤为：将氟尼辛粗品加入到三乙胺和乙醇的混合溶剂中，搅拌，升温至溶解，控制温度至75℃-80℃，降温至5℃-10℃，析晶1.5-2h后，离心，滤饼和滤饼湿重2.5-3倍重量的水投入反应釜中，用盐酸调节pH＝5-6，离心，滤饼干燥得精制品。
CN201910883733.7A 2019-09-18 2019-09-18 一种氟尼辛的精制方法 Pending CN110483389A (zh)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1803773A (zh) * 2006-01-24 2006-07-19 山东鲁抗舍里乐药业有限公司 氟尼辛葡甲胺的合成提取精制方法
CN102442944A (zh) * 2011-12-14 2012-05-09 齐鲁动物保健品有限公司 一种氟尼辛的制备方法
CN103694167A (zh) * 2013-12-11 2014-04-02 威海雅瑞生物科技有限公司 一种氟尼辛葡甲胺的合成方法
CN104193674A (zh) * 2014-08-27 2014-12-10 济南久隆医药科技有限公司 一种氟尼辛葡甲胺的合成方法
CN108586327A (zh) * 2018-04-25 2018-09-28 山东久隆恒信药业有限公司 一种氟尼辛的合成方法
CN109206365A (zh) * 2018-09-13 2019-01-15 龙岩台迈三略制药有限公司 一种氟尼辛葡甲胺的制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1803773A (zh) * 2006-01-24 2006-07-19 山东鲁抗舍里乐药业有限公司 氟尼辛葡甲胺的合成提取精制方法
CN102442944A (zh) * 2011-12-14 2012-05-09 齐鲁动物保健品有限公司 一种氟尼辛的制备方法
CN103694167A (zh) * 2013-12-11 2014-04-02 威海雅瑞生物科技有限公司 一种氟尼辛葡甲胺的合成方法
CN104193674A (zh) * 2014-08-27 2014-12-10 济南久隆医药科技有限公司 一种氟尼辛葡甲胺的合成方法
CN108586327A (zh) * 2018-04-25 2018-09-28 山东久隆恒信药业有限公司 一种氟尼辛的合成方法
CN109206365A (zh) * 2018-09-13 2019-01-15 龙岩台迈三略制药有限公司 一种氟尼辛葡甲胺的制备方法

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