固体光气法合成洛莫司汀

Synthesis of lomustine utilizing triphosgene

以固体光气 (三光气 )为起始原料 ,经过在无水甲苯溶液中与环己胺反应生成环己基异氰酸酯 ,再经与氨基乙醇和氯化亚砜的一锅法反应生成 1 (2 氯乙基 ) 3 环己基脲 (氯化物 ) ,最后再亚硝化 ,即得洛莫司汀。原料易得 ,各步反应条件温和 ,操作方便 ,步骤比文献方法 (4步 )减少一步 ,总收率由文献方法的 2 3 7%提高为 4 9 8% ,适于工业规模制备。

Cyclohexyl isocyanate was synthesized by using triphosgene as the starting material through the reaction with cyclohexylamine in the anhydrous toluene,then through the reaction with amino-ethanol and thionyl chloride to produce 1-(2-chloroethyl)-3-cyclohexyl urea(chloride),at last through nitrosation to produce lomustine.The starting material is very easy to get,the reaction conditions are moderate and the operation is convenient.The reaction steps were lessened when comparing with the literature method(four steps),and the total yield reached 49.8% from 23.7% of the literature method.This method is suitable for industrial producing.