- Process Research and Development of an Enantiomerically Enriched Allyic Amine, One of the Key Intermediates for the Manufacture of Synthetic Tetracyclines
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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.
- Zhang, Wu-Yan,Hogan, Philip C.,Chen, Chi-Li,Niu, John,Wang, Zhimin,Lafrance, Danny,Gilicky, Olga,Dunwoody, Nicholas,Ronn, Magnus
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p. 1784 - 1795
(2015/12/01)
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- HEPATITIS C INHIBITORS AND USES THEREOF
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This disclosure relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 133
(2012/07/13)
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- 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
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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.
- Riess, Regine,Schoen, Michael,Laschat, Sabine,Jaeger, Volker
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p. 473 - 479
(2007/10/03)
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