| 第 48 卷第 2 期 |  | Vol. 48 No. 2 | | 2018 年 4 月 | Apr 2018 |
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所屬欄目：醫藥及中間體
2-氰基-4-吡啶羧酸甲酯的合成工藝改進(jìn) |
| 門(mén) 靖，丁志新，曹衛凱，安 敏
（西安萬(wàn)隆制藥股份有限公司，陜西 西安 710119） |
| 摘 要：對2-氰基-4-吡啶羧酸甲酯的合成工藝進(jìn)行了優(yōu)化。以2-甲基-4-吡啶羧酸甲酯（2）為起始原料，經(jīng)氧化、酰胺化、脫水3步反應制備了目標化合物，其結構經(jīng)1H NMR和MS確證，總收率為53.0%。通過(guò)單因素實(shí)驗的方法研究了投料比、析晶溫度、反應時(shí)間等因素對產(chǎn)物的影響，優(yōu)化工藝條件：n（2）∶n（高錳酸鉀）= 1.0∶2.5，析晶溫度為0 ~5℃；n（2-羧基-4-吡啶羧酸甲酯）∶n（二氯亞砜）= 1.0∶1.4，反應時(shí)間為5~6 h；脫水反應選擇三氟乙酸酐-三乙胺體系作為脫水劑。工藝過(guò)程操作簡(jiǎn)單、反應條件溫和，易于放大生產(chǎn)，具有較好的實(shí)際應用價(jià)值。 |
| 關(guān)鍵詞：2-甲基-4-吡啶羧酸甲酯；2-氰基-4-吡啶羧酸甲酯；三氟乙酸酐-三乙胺 |
| 中圖分類(lèi)號：R914 文獻標識碼：A 文章編號：1009-9212（2018）02-0055-04 |
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| An Improved Process for the Preparation of 2-Cyano-4-pyridinecarboxylic Acid Methyl Ester |
| MEN Jing, DING Zhi-xin, CAO Wei-kai, AN Min
(Xi'an WanLong Pharmaceutical Co., Ltd., Xi'an 710119, China) |
| Abstract：2-Cyano-4-pyridinecarboxylic acid methyl ester was synthesized from the 2-methyl-4-pyridinecarboxylic acid methyl ester (2) through a series of reactions including oxidation, amidation and dehydration reaction. The structure was confirmed by 1H NMR and MS. The overall yield was up to 53.0%. The factors including material ratio, crystallization temperature and reaction time were studied by single factor experiment. The preferential experimental results showed that the optimal reaction condition as follows: the ratio of compound 2 to potassium permanganate was 1.0∶2.5; the crystallization temperature was 0~5℃; the ratio of compound 3 to thionyl chloride was 1.0∶1.4; and the reaction time was 5~6 h. Trifluoroacetic anhydride-triethylamine system could play a good part in the dehydration reaction. This improved synthetic route had the advantages of easy preparation and mild reaction conditions, which was suitable for further application and good for practical application values. |
| Key words：2-methyl-4-pyridinecarboxylic acid methyl ester; 2-cyano-4-pyridinecarboxylic acid methyl ester; trifluoroacetic anhydride-triethylamine |
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作者簡(jiǎn)介：門(mén) 靖（1986-），男，陜西西安人，工程師，主要從事原料藥開(kāi)發(fā)及申報資料撰寫(xiě)工作（E-mail：1257391857@qq.com）。
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收稿日期：2018-04-06
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