Synthesis And Process Study Of Some Fluorinated Pharmaceutical Intermediates

4-fluorocyclohexanone,2,2-difluoropropanol and 2-amino-3-bromo-5-fluoropyridine are important intermediates for the synthesis of anticancer drugs,anti-leukemia drugs and antibiotic drugs,respectively,with high value and market The advantages of good prospects,but due to the current high cost of raw materials,low yield of target products and cumbersome synthetic routes,the paper re-optimizes the synthetic route of these three target compounds.The realization of low raw material cost,high product yield and the optimal reaction conditions for pilot production.The target product 1 is based on 1,4-cyclohexanedione monoethylene ketal.The addition of an organic base pyridine during the DAST fluorination process effectively avoids the production of by-products,further through hydrogenation and hydrolysis.The target product4-fluorocyclohexanone was synthesized by reaction,and the product yield was 78.3%,and the purity was 98.5%.The target product 2 was obtained by using ethyl pyruvate as a raw material,and the target product 2,2-difluoropropanol was synthesized by DAST fluorination and sodium borohydride reduction,and the product yield was 82.4%,and the purity was98.9%.The target product 3 was synthesized from 2-amino-5-nitropyridine by the optimization and design of the synthesis route.The product2-amino-3-bromo-5-fluoropyridine was synthesized,and the product yield was 72.1%,and the purity was 98.5%.In this thesis,the synthesis route of three fluorine-containing compounds was systematically studied from the molar ratio of feed,the amount of fluorinating agent and the kind of solvent,and the best process conditions were obtained.The target compounds and their intermediates were constructed using 1H NMR and 19 F NMR structures.Characterization,purity is detected by GC.Moreover,4-fluorocyclohexanone and2-amino-3-bromo-5-fluoropyridine have been customized for the 100-gram project,and2,2-difluoropropanol has been pilot-produced.