3-methylaminopiperidine, an intermediate for the manufacturing of Balofloxacin, was synthesis from nicotinic amide in four steps. 3-aminopyridine was prepared from the Hofmann reaction of nicotinic amide in 93% yield. Treatment of 3-aminopyridine with AFA at room temperature gave 3-formamidopyridine in 95% yield. 3-methylaminopyridine was prepared via reduction of 3-formamidopyridine with LiAlH4. The reaction parameters such as the addition way, the quantity of THF and LiAlH4 used, reaction temperature and reaction time were optimized and 95% yield of 3-methylaminopyridine were obtained. Finally 3-methylaminopyridine was reduced to 3-methylaminopiperidine with Na in ethyl alcohol. The yield of 3-methylaminopiperidine hydrochloride was 90%. TLC, HPLC, 1H-NMR and GC-MS analyzed the purity and structure of the intermediates and the final products. |