盐酸左西替利嗪的合成工艺改进

Improved Synthesis of (R)-Cetirizine

目的 探究盐酸左西替利嗪(1)的合成工艺改进。方法 以(R)-4-氯二苯甲胺、三(2-氯乙基)胺为原料,经环合反应得到化合物8;8与2-羟基乙酸乙酯经缩合得化合物7;7经水解、成盐酸盐得到终产物1,纯度99.7%,光学纯度99.2%。结果 改进后的工艺收率由文献的23.4%~42.2%提高到47.0%[以(R)-4-氯二苯甲胺计],纯度由99.1%提高到99.7%。结论 改进后的工艺原料价廉易得,成本低,原子利用率高,反应条件温和,适于工业化生产。

OBJECTIVE To explore the improvement synthetic process of levocetirizine dihydrochloride(1). METHODS(R)-4-chlorobenzylamine and tris(2-chloroethyl)amine were used as raw materials to abtain compound 8 via cyclization reaction.Compound 8 was condensed with ethyl 2-hydroxyacetate to produce compound 7.The target compound 1 was obtained after compound 7 being hydrolyzed and neutralized by hydrochloric acid.Its purity was 99.7%, and the optical purity was 99.2%. RESULTS The improved process yield was increased from 23.4% to 42.2% in the literature to 47% [based on(R)-4-chlorobenzylamine], and the purity increased from 99.1% to 99.7%. CONCLUSION The improved synthetic process have some advantages such as cheaper material, low cost, high atomic utilization rate, mild reaction conditions.This process is suitable for for manufacture.