摘要
目的改进瑞舒伐他汀钙重要中间体的合成工艺。方法以对氟苯甲醛、异丁酰乙酸甲酯、尿素为原料,经环合、氧化、亲核取代、水解还原得到瑞舒伐他汀钙重要中间体嘧啶甲基醇5。结果工艺改进后,嘧啶甲基醇衍生物5的总收率由55.3%提高到77.1%。结论新工艺对中间体1的反应溶剂和中间体3的结晶溶剂进行优化;采用氢氧化钠的乙醇-水溶液将中间体3水解得中间体4,再还原为嘧啶甲基醇5,使制备中间体5的操作简单,成本更低,适合工业化生产。
Objective To improve the manufacturing process of the important intermediate of rosuvastatin calcium. Methods Starting with 4-fiuorobenzaidehyde, isobutyryiacetate and urea in the presence of a protonic compound, cuprous chloride as catalyzer, then through methyiation, oxidation, necieophiiic substitution, hydrolysis and reduction, the pyrimidine methyl alcohol intermediate 5 of rosuvatatin was synthesized. Results After process improvements, the overall yield of the pyrimidine methyl alcohol derivative 5 was increased from 55.3% to 77.1%. Conclusion The new process optimized the reaction solvent of intermediate 1 and the crystallization solvent of 3. It was hydrolysised intermediate 3 by sodium hydroxide in ethanol water solution and reducted intermediate 4 to prepare pyrimidine methyl alcohol 5. Such method is simple and lower cost. It is more suitable for industrial production.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2015年第4期256-259,294,共5页
Chinese Journal of Antibiotics
关键词
瑞舒伐他汀钙
水解
还原
Rosuvastatin calcium
Hydrolysis
Reduction
