恩替卡韦关键中间体4-甲氧苯基二苯基氯甲烷的合成工艺研究

Synthesis of Key Intermediate 4-Methoxytriphenylchloromethane of Entecavir

以苯(2)为原料,与四氯化碳发生傅-克烷基化反应,制得二苯基二氯甲烷(3),优化条件下收率84.7%;3和苯甲醚再发生傅-克烷基化反应,得到恩替卡韦关键中间体4-甲氧苯基二苯基氯甲烷(1),优化条件下收率85.9%,产品纯度99.1%。考察了催化剂的结构、催化剂的量、反应温度等因素对收率的影响。通过^(1)H NMR、^(13)C NMR和ESI-MS确证了1及中间体的结构。

Dichlorodiphenylmethane(3)was obtained from benzene(2)and carbon tetrachloride through FriedelCrafts alkylation with a yield of 84.7%.Then 4-methoxytriphenylchloromethane(1)was synthesized from 3 and anisole through Friedel-Crafts alkylation with a yield of 85.9%and a chromatographic purity of 99.1%.The affecting factors including the structure,ratio of the catalysts,and the reaction temperature were investigated.The structures of the compound 1 and intermediate were characterized by ^(1)H NMR,^(13)C NMR and ESI-MS.