Process Research and Development of an Enantiomerically Enriched Allyic Amine, One of the Key Intermediates for the Manufacture of Synthetic Tetracyclines

摘要

A robust, cost-effective, and high yielding Manufacturing process for enantiomerically enriched (S)-allylic amine 3, a key intermediate for fully synthetic tetracyclines have been developed. Two-novel and scalable asymmetric vinylations resulting high-to-excellent stereoselectivity have been developed for the key step. The final product is purified by an efficient Crystallization of a L-tartaric salt. The process described has been used to manufacture similar to 350 kg of the tartaric salt of 3 With 99.0% ee in 8 steps (35% overall yield) from cheap and readily available dimethyl maleate.