环丙沙星的合成工艺改进

Process Improvement on the Synthesis of Ciprofloxacin

对环丙沙星(1)的合成工艺进行了改进。在2,4-二氯-5-氟苯乙酮和碳酸二甲酯的缩合反应中,用甲醇钠代替氢化钠;在乙氧亚甲基化反应中,用N,N-二甲基甲酰胺二甲缩醛代替价格昂贵的原甲酸三乙酯;在哌嗪取代反应中,采用硼络合物的方法,提高了取代反应的选择性。1及其中间体的结构经1H NMR确证。缩合反应收率80.6%,亚甲基化和胺化的总收率70.8%,哌嗪取代收率90.8%。

Ciprofloxacin （1） was synthesized by condensation, amination, cyclization, hydrolysis, piperazination from 2, 4-dichloro-5-fluoro-acetophenone. The sodium hydride was substituted by the sodium methylate in the condensation reaction; moreover, the expensive triethyl orthoformate was replaced by the N,N-dimethyl-formamidedimethyl acetal; boric coordination complex was used in the piperazination with higher selectivity. The yield of condensation, amination and piperazination were 80. 6%, 70. 8% and 90.8%, respectively. The structures of 1 and some key intermediats were confirmed by ^1H NMR.