冰片衍生物N-Boc基脱保护工艺研究

Study on the Deprotection of N-Boc of Borneol Derivatives

以磷酸作为脱保护剂对冰片衍生物N-Boc保护基进行脱保护合成L-脯氨酸冰片酯与L-丙氨酰-L-脯氨酸冰片酯,考察了各反应条件对两种冰片酯产率的影响,确定了Boc-L-脯氨酸冰片酯中N-Boc脱除的最佳工艺为:反应溶剂为二氯甲烷,反应物与脱保护剂的当量比为1∶10,反应时间为18 h,除杂液为二氯甲烷,碳酸钠用量为磷酸体积的20倍;Boc-L-丙氨酰-L-脯氨酸冰片酯中N-Boc脱除的最佳工艺为:反应溶剂为二氯甲烷,反应物与脱保护剂的当量比为1∶5,反应时间为7 h,除杂液为石油醚与乙酸乙酯(体积比为2∶1),碳酸钠用量为磷酸体积的20倍。该法制备产物具有杂质少、产率高的优势。

Phosphoric acid was used as deprotection agent to deprotect the N-Boc protection group of borneol derivative to synthesize L-proline bornyl ester and L-propionyl-L-proline bornyl ester. The effects of reaction condition were investigated. The optimum reaction conditions of L-proline borneol ester were obtained as follows:reaction solvent was dichloromethane, the equivalent ratio of reactant to deprotective agent was 1∶10, the reaction time was 18 h, the impurity removal liquid was dichloromethane, washing sodium carbonate was 20 times as volume as phosphoric acid. The optimum process of N-Boc removal from Boc-L-alanyl l-proline bornyl ester was as follows:dichloromethane was the solvent, the equivalent ratio of reactant to deprotective agent was 1∶5, the reaction time was 7 h, the volume ratio of petroleum ether to ethyl acetate was 2∶1, washing sodium carbonate was 20 times as volume as phosphoric acid. The process had the advantages of less impurities and high yield.