Mesylate Of New Process For Synthesis Of Fluorine Sand Star

A new route was elaborated to synthesize a novel veterinary drug- danofloxacin mesylate(1) (FQS ) and the result was got in the following aspects:Firstly, the important intermediate of danofloxacin mesylate: (1S,4S) -2-Methyl-2,5 diazabicyclo[2.2.1]heptane Dihydrobromide(2) was synthesized form Jrara-4-hydroxy-L-proline (3) in the total yield of 64% by using a new route with five steps(schemel).Scheme 1Secondly, danofloxacin mesylate was synthesized form (1S,4S) -2-Methyl-2,5 diazabicyclo[2.2.1]heptane Dihydrobromide in the total yield of 78% with two steps(scheme2). The quality of target compound(1)can fit to the quality standard.Thirdly, a novel compound (2S,4R) -l-(4-Tolylsulfonyl)-2-(cholomethyl) -4-((4-tolylsulfonyl)oxy)pyrrolidine (8) was synthesized, its structure was identified by spectroscopic methods: 1H-NMR, 13C-NMR, 1H-'Hcosy, HSQC.Fourthly, to achieve the best condition, each step had been studied carefully: (1). The N-tosylated-fr<3ra-4-hydroxyl-L-proline(4) was reduced with potassiumborohydride and Lewis acid. To increase temperate by high pressure. The compound (5) was got in the yield of 95% by this method. The best mole rate of Lewis acid and compound (4) andKBHt, was 1:0.25:2, The best temperature is 90@ within 10h. The best volume of MeOH is compound (4) (weight) :MeOH (volume) =1:6.(2). (2S,4R) -2-(Hydromethyl)-4-hydroxy-l-(4-tolylsulfonyl)pyiTolidine (5) was tosylated and chlorinated with p-TsC\ in toluene and triethylamine instead of pyridine, The best condition of reaction was compound ( 5 ): EtaN : toluene (weight) =1:1.3:3. a new compound (8) was got with high yield and the high yield of compound (7)could be got with the cyclization of compound ( 8 ).Fifthly, the new route was used in the workshop where danofloxacin mesylate could be produced lOt every year. The average yield of five times was 48.8% , slightly less than the yield of 50% in lab. The operation was simple. The technique was stable and the running of facilities was normal. The yield increased by 25.5% than before. The cost of new route was 1,195,390 yuan/t, 2,700,000 yuan/t was decreased than before. Its economic effect was notable.