An improved process for chiron synthesis of the atorvastatin side chain

作者：Xiong Fang Jun; Li Jie; Chen Xiao Fei; Chen Wen Xue; Chen Fen Er^*

来源：Tetrahedron: Asymmetry , 2014, 25(16-17): 1205-1208.

DOI：10.1016/j.tetasy.2014.07.002

An improved and practical synthesis of tert-butyl ((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetate 3 has been developed for supplying this key chiral side-chain of atorvastatin by using a Blaise reaction of (S)-4-chloro-3-((trimethylsilyl)oxy)butanenitrile 7 and the Raney Ni catalyzed hydrogenation of tert-butyl 2-((4R,6R)-6-(-2-oximeethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate 12 as the key steps. This nine-step route from (R)-epichlorohydrin afforded the target compound in 55% overall yield of high chemical and enantiomeric purity.

• 出版日期2014-9-15
• 单位复旦大学