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

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 in high-to-excellent stereoselectivity have been deve...

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Bibliographic Details
Published in:Organic process research & development 2015-11, Vol.19 (11), p.1784-1795
Main Authors: Zhang, Wu-Yan, Hogan, Philip C, Chen, Chi-Li, Niu, John, Wang, Zhimin, Lafrance, Danny, Gilicky, Olga, Dunwoody, Nicholas, Ronn, Magnus
Format: Article
Language:English
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Summary: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 in 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 ∼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.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.5b00274