205115-33-9Relevant academic research and scientific papers
Process Research and Development of an Enantiomerically Enriched Allyic Amine, One of the Key Intermediates for the Manufacture of Synthetic Tetracyclines
Zhang, Wu-Yan,Hogan, Philip C.,Chen, Chi-Li,Niu, John,Wang, Zhimin,Lafrance, Danny,Gilicky, Olga,Dunwoody, Nicholas,Ronn, Magnus
, p. 1784 - 1795 (2015)
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.
Evaluation of protecting groups for 3-hydroxyisoxazoles - Short access to 3-alkoxyisoxazole-5-carbaldehydes and 3-hydroxyisoxazole-5-carbaldehyde, the putative toxic metabolite of muscimol
Riess, Regine,Schoen, Michael,Laschat, Sabine,Jaeger, Volker
, p. 473 - 479 (2007/10/03)
The regioselectivity of the 3-hydroxyisoxazole-5-ester 1 is studied with respect to O- versus N-alkylation. 3-O-Alkyl products 2 are highly favoured with benzyl, benzhydryl, and allyl bromide (≥ 91:9), in contrast to known uses of 5-alkyl-3-hydroxyisoxazoles or when methylation with diazomethane (or methyl iodide) is effected. Methoxymethylation leads to the N-substituted isoxazolinone 3e only. On reduction with DIBAH, the esters 2 afford 3-O-protected 3-hydroxyisoxazole-5-carbaldehydes 4 (75-98%). For removal of the benzyl protecting groups, three variations (HBr/HOAc, H2/ Pd/BaSO4, NBS/AIBN) were found useful with 5-ester, 5-formyl, and 5-hydroxymethyl derivatives. The free 3-hydroxy-5-carbaldehyde 9, the putative toxic metabolite of the GABA agonist muscimol, is prepared accordingly. The O-protected 3-hydroxyisoxazole-5-carbaldehydes 4 constitute versatile intermediates in various routes to analogues of CNS-active amino acids and can now be obtained in a highly efficient manner.
