本文選題：糖尿病 + 磷酸西他列汀　； 參考：《浙江大學(xué)》2013年碩士論文

【摘要】：磷酸西他列汀是一種新型二肽基肽酶抑制劑(DPP-IV抑制劑),對2型糖尿病的治療效果良好。 本論文主要是針對磷酸西他列汀主鏈中間體進(jìn)行合成研究,文獻(xiàn)報道的磷酸西他列汀主鏈中間體3-氧代-4-(2,4,5-三氟苯基)丁酸乙酯的合成主要是以2,4,5-三氟苯乙酸和2,2-二甲基-1,3-二氧六環(huán)-4,6-二酮為原料。本論文設(shè)計了一條以1,2,4-三氟苯和丙二酸二乙酯為原料,具有自主知識產(chǎn)權(quán)的磷酸西他列汀主鏈中間體的合成路線。包括五步反應(yīng)：氯甲基化、制成格式試劑、酯的水解、制成酰氯、格式反應(yīng),最終得到純度為97.5%的3-氧代-4-(2,4,5-三氟苯基)丁酸乙酯。 新工藝路線具有起始原料廉價易得,生產(chǎn)成本低,各步驟的反應(yīng)條件溫和,操作安全環(huán)保的優(yōu)點(diǎn)。其中氯甲基化的收率達(dá)到85.1%,高于文獻(xiàn)的75%。 制備格式試劑使用2-甲基四氫呋喃為溶劑,降低偶合副反應(yīng)的發(fā)生,提高了反應(yīng)的收率,減少了溶劑使用量。 另外,對文獻(xiàn)報道的以2,4,5-三氟苯乙酸和丙二酸亞異丙酯為原料,得到3-氧代-4-(2,4,5-三氟苯基)丁酸乙酯的工藝,進(jìn)行了溶劑、反應(yīng)溫度等方面的優(yōu)化。
[Abstract]:Cetastatin phosphate is a new type of dipeptidyl peptidase inhibitor DPP-IV, which has a good therapeutic effect on type 2 diabetes.In this thesis, the main chain intermediates of cetastatin phosphate were synthesized.The synthesis of ethyl 3-oxo-4-trifluorophenyl 3-oxo-4-trifluorophenyl) -3-oxo-4-difluoro-5-trifluorophenyl) ethyl phosphate was reported in the literature. The synthesis of ethyl butyrate mainly consisted of 2o 4N 5- trifluorophenyl acetic acid and 2o 2 dimethyl-1n 3 dioxane 3 dioxane 6 dione as raw materials.In this paper, a synthetic route of cetaletine phosphate intermediate with independent intellectual property rights was designed, which was made from 1o 2o 4 trifluorobenzene and diethyl malonate.The reaction includes five steps: chloromethylation, preparation of formative reagent, hydrolysis of ester, preparation of acyl chloride, format reaction, and the final synthesis of ethyl 3-oxo-4-trifluorophenyl) butyrate with a purity of 97.5%.The new process has the advantages of cheap raw material, low production cost, mild reaction conditions and safe operation.The yield of chloromethylation was 85.1%, which was higher than that in the literature (75.1%).When 2-methyltetrahydrofuran was used as solvent, the coupling side reaction was reduced, the yield of the reaction was increased, and the amount of solvent was reduced.In addition, the process of synthesis of ethyl 3-oxo-4-trifluorophenyl trifluorophenyl trifluoroacetic acid and isopropyl malonate, which was reported in the literature, was optimized in terms of solvent, reaction temperature and so on.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：TQ463

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