瑞舒伐他汀中间体的合成工艺改进

Improvement in Synthesis Method of the Intermediate of Rosuvastatin

采用B iginelli嘧啶酮缩合反应,以4-氟苯甲醛、异丁酰乙酸甲脂和硫脲为原料,在质子酸存在下经缩合、甲基化、氧化、亲核取代、还原和氧化反应,合成了降血脂药物瑞舒伐他汀(Rosuvastatin)的中间体嘧啶醛化合物(Ⅶ),总收率为32.5%,与H irai K所申请的专利(US 5 260 440,1993)的方法相比,不仅缩短了反应步骤,而且收率提高了14.5%。化合物的结构经1HNMR,IR和MS进行了确证。

Applying the Biginelli reaction, reacting 4-fluorobenzaldehyde with methyl isobutyrylacetate and thiourea in the presence of a protonic compound, then through methylation, oxidation, necleophilic substitution, reduction and oxidation, the pyrimidine aldehyde intermediate of Rosuvatatin （ for reduction of cholesterol levels in patients with hypercholesterolaemia）was synthesized in 32.5% yield. Compared with the literatures, not only the synthesis step was shorten,but also the yield was improved by 14.5 %. Structures of the compounds were confirmed by ^1HNMR,IR and MS.