N-叔丁基二甲基硅基-L-脯氨醇的研制

Preparation of N-tert-butyl-dimethylsilyl-L-prolinol

以L-脯氨酸为起始原料,与叔丁基二甲基氯硅烷反应制得中间产物N-叔丁基二甲基硅基-L-脯氨酸。进一步与硼氢化钠反应制得目标产物N-叔丁基二甲基硅基-L-脯氨醇。采用核磁共振波谱和质谱分析了产物结构。研究了物料配比、反应时间对中间产物合成的影响,以及物料配比、反应温度、析晶溶剂种类对目标产物合成的影响。结果表明,较佳工艺为:合成中间产物时叔丁基二甲基氯硅烷与L-脯氨酸的量之比1.3∶1、反应时间3~4 h;合成目标产物时硼氢化钠与中间产物的量之比2∶1、反应温度30~40℃、环己烷作析晶溶剂。该工艺路线条件温和、后处理简单,总收率为70.8%。

The intermediate compounds of N-tert-butyl-dimethylsilyl-L-proline were synthesized from L-proline and tert-butyl-dimethylchlorosilane.The target product of N-tert-butyl dimethylsilyl-L-prolinol was further prepared by reaction with sodium borohydride.The structure of N-tert-butyl dimethylsilyl-L-prolinol was characterized by1 H NMR and MS.The effects of material ratios,reaction time on the synthesis of intermediates,as well as the effects of material ratio,temperature and the types of crystallization solvent on the synthesis of the target products were studied.The results show that the optimum process is as following:the ratio of amount of n(tert-butyldimethylsilyl chloride)to n(L-proline)is 1.3∶1.0,and reaction time is 3~4 h;the ratio of the amount of n(sodium borohydride)to n(intermediate)is 2∶1,and reaction temperature is 30~40℃with cyclohexane as the crystallization solvent.The process conditions are mild,with a simple post-treatment and total yield of 70.8%.