左旋盐酸西替利嗪的合成工艺改进

Improved synthesis of levocetirizine dihydrochloride

目的研究左旋盐酸西替利嗪的合成工艺。方法以氯代苯和苯甲酰氯为起始原料,经傅克酰化、还原胺化得到左旋盐酸西替利嗪的关键中间体4-氯双苯胺(4),4再经拆分、成环、缩合制得左旋盐酸西替利嗪。结果与结论目标化合物的结构经红外光谱、元素分析确证,总收率为9.96%。该工艺操作简便,适用于工业化生产。

Aim To improve the synthetic process of levocetirizine dihydrochloride. Methods 4-Chloro- phenylphenylmethylamine（4）, a key intermediate of cetirizine, was obtained via Friedel-Crafts reaction from 1- chlorobenzene with benzoyl chloride, followed by separating with L-（ ＋ ）tartaric acid to give R enantiomer（5） of 4. Cyclization of 5 with bis（2-chloroethyl） amine hydrochloride to afford （R）-4-chlorophenylphenylmethyl piperazine （6）, then 6 was subsequendy oondensed to levocefirizine dihydrochloride（1）. Results and conclusion The structure of target compound was confirmed by IR, elemental analysis, and the overall yield was 9.96 %. The improved method was easy for synthesis and suitable for industrial manufacturing.