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在超声辐射下,以(S)-2-哌啶甲酸(Ⅱ)为原料,依次与氯化亚砜、2,6-二甲基苯胺反应制得(S)-N-(2,6-二甲基苯基)-2-哌啶甲酰胺(Ⅴ),而后,Ⅴ与溴丙烷发生N-丙基化反应,经盐酸成盐得到目标化合物手性纯的盐酸盐罗哌卡因(Ⅰ)。该文考察了超声辐射条件下反应溶剂、反应温度和反应时间等因素对反应收率的影响。优化后的工艺条件与传统加热方法相比,具有条件温和、反应时间短、收率高等优点。得到的最佳反应条件为:以甲苯为酰氯和酰胺反应溶剂,酰氯化反应条件为40℃超声反应1.5 h,丙基化反应条件为40℃超声反应1 h,盐酸罗哌卡因的收率为57.8%,[α]2D5=-6.7°(c2,H2O)。部分中间体和目标产物的结构通过熔点和核磁共振波谱进行了表征。
(S) -N- (2,6-dimethyl) aniline was prepared by the reaction of (S) -2-piperidinecarboxylic acid with the thionyl chloride and 2,6- Dimethylphenyl) -2-piperidinecarboxamide (V), and then, V and bromopropane N-propylation reaction of salt into the target compound hydrochloride chiral pure hydrochloride ropivacaine ( Ⅰ). In this paper, the effects of reaction solvent, reaction temperature and reaction time on the reaction yield were investigated under ultrasonic irradiation. Compared with the traditional heating method, the optimized process conditions have the advantages of mild conditions, short reaction time and high yield. The optimal reaction conditions were as follows: the reaction temperature was 40 ℃ for 1.5 h and the reaction temperature was 40 ℃ for 1 h. The yield of ropivacaine hydrochloride Of 57.8%, [α] 2D5 = -6.7 ° (c2, H2O). The structures of some intermediates and target products were characterized by melting point and nuclear magnetic resonance spectroscopy.