卡培他滨的合成

Synthesis of Capecitabine

以5'-脱氧-5-氟-尿苷为原料,经原碳酸四乙酯保护后,氯代、氨解,得到2',3'-O-二乙氧甲叉基-5'-脱氧-5-氟-胞苷4,4与氯甲酸正戊酯酰化后,在温和的酸性条件下脱掉保护基,得到卡培他滨。总收率36.8%。中间体及终产物均经过1H-NMR、MS谱确证。该方法操作简单,收率较高且产物易于分离纯化,可以用于大规模制备卡培他滨。

Capecitabine was synthesized from Doxifluridine by discriminative protection with tetraethyl orthocarbonate,chlorination,aminolysis,to provide 5 ＇-deoxy-2 ＇,3 ＇-O-（ diethoxymethylene）-5-fluoro-cytidine 4, which was subjected to acetylation with pentyl chloroformate,and deprotection in the weak acidic condition. The overall yield was up to 36. 8%. Intermediates and capecitabine were identified by both1H-NMR and MS This method had the advantages of simple procedure,high yield and easy purification. So this new method was more suitable for scale-up production.