101459-87-4Relevant academic research and scientific papers
Efficient Synthesis of the Nucleus of Atorvastatin Calcium
Xing, Yuzhi,Chen, Shipeng,Zhou, Yingtao,Liu, Na,Chen, Ligong,Li, Yang
, p. 2832 - 2840 (2015)
An efficient synthetic route for the parent nucleus of atorvastatin calcium was successfully established through the modification of the related reactions. Under the optimized conditions, compound 1 was obtained in 61.2% yield (lit. 51.4%) from methyl isopropyl ketone via five steps. Two impurities generated by the aldol condensation of methyl isopropyl ketone were identified by gas chromatography-mass spectrometry and their generation can be inhibited by reducing the mixing time of methyl isopropyl ketone and NaH. One oxybromination protocol with hydrogen peroxide was employed to make the best of bromine. A debromination by-product was isolated and confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry and its generation mechanism was discussed. The impurity can be inhibited by protecting the reaction from light and easily removed by recrystallization.
Asymmetric Aza-Wacker-Type Cyclization of N-Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters
Kou, Xuezhen,Shao, Qihang,Ye, Chenghao,Yang, Guoqiang,Zhang, Wanbin
, p. 7587 - 7597 (2018/06/04)
We have developed an asymmetric aza-Wacker-type cyclization of N-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the C=C double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a syn-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is cis to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps.
