5777-21-9Relevant academic research and scientific papers
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.
