Efficient Construction of the Nucleus of Rosuvastatin Calcium
Yingtao Zhou, Chenhui Lin, Yuzhi Xing, Ligong Chen, Xilong Yan · Journal of Heterocyclic Chemistry · 2016
A novel and efficient five‐step synthetic route, including a Biginelli reaction, dehydrogenation, chlorination, sulfonamidation, and reduction, for the core of Rosuvastatin was established. All steps were systematically studied. Tert‐butylhydroperoxide aqueous solution was applied in the dehydrogenation instead of nitric acid.N,N‐dimethylaniline was employed as a catalyst to accelerate the chlorination proceeding smoothly, and its catalytic mechanism is discussed. In the sulfonamidation, the conversion of compound5was obviously improved by use of NaH and acetonitrile. In addition, two sulfonamidation side products6and7were detected and isolated. Thus, under the optimized reaction conditions, the target product was obtained in 60.4% total yield, much higher than the reported yield (36.4%).