Synthesis And Chemical Process Of 4-(3-(Tert-Butyldimethylsilyloxy)-1, 1-difluoropropan-2-yl) Morpholine

Quinolones are a class of antibacterials synthetic antibiotics, which can effectively inhibit and kill pathogenic micro-organisms to treat bacterial infections. It is widely used in clinical treatment of various infectious diseases with a broad spectrum antimicrobial, antibacterial and strong, easy administration, oral absorption, high tissue concentrations, other antibacterial drugs, and moderate price without cross-resistance and adverse reactions.The dissertation is mainly focused on the synthesis of 4-(3-(tert-butyldimethylsilyloxy)-1,1-difluoropropan-2-yl)morpholine, which is a key intermediate of modified derivatives as antimicrobial quinolone agents. Based on the chemical structure of the target compound, we utilized the disconnection method via retrosynthetic analysis to design several synthetic routes. Using diethyl methyl ester as the starting material, it was prepared via six-steps, such as bromination, coupling reaction, reduction, hydroxyl protection, hydroxyl oxidation and fluorination. Each reaction step was optimized with proper reagents and synthetic methods. The total yield of six step reaction was 12.3%.The reaction temperature is important, because it can effect the product produce.The overall reaction route has been well developed, and pilot experiments have been successfully tested with optimized chemical process. However, the purification process in each step and cost should be further improved.