Synthesis of 3-isoxazolols revisited. Diketene and (β-ketoesters as starting materials

Abstract

3-Isoxazolols can be made in good yields from β-ketoesters or diketene and hydroxylamine, provided that pH is kept at about 10 throughout the reaction, and that the reaction mixture is quenched with an excess of strong mineral acid. This suppresses the formation of 5-isoxazolones, which are otherwise normally the main products of the reaction.

A simple and effective strategy for labeling cysteine sulfenic acid in proteins by utilization of β-ketoesters as cleavable probes

“…The envisioned advantage of the ester linkage in C165S AhpC-1 was the potential reaction with hydroxylamine (NH 2 OH) to generate 3-methyl-5-isoxazolone. 8 As anticipated, the yield was nearly quantitative after treatment with 50 mM NH 2 OH for 1 h at 37 1C (product peak at 20 697 amu in Fig. S1B, ESIw).…”

Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria

“…Compound 88 was then subjected to a Masamune−Claisen condensation, providing keto-ester 89 in reasonable yield. 69 Condensation with hydroxylamine generated the hydroxyisoxazole ring (90), 70 and deprotection with HCl completed the synthesis of 19.…”

Cyclocondensation of Hydroxylamine with 1,3‐Bis(het)arylmonothio 1,3‐Diketones and 1,3‐Bis(het)aryl‐3‐(methylthio)‐2‐prop­enones: Synthesis of 3,5‐Bis(het)arylisoxazoles with Complementary Regioselectivity

“…Intramolecular heterocyclization via intermediates 7 – 8 then gives isoxazoles 5 exclusively, in which the het(aryl) group attached to the thiocarbonyl group in 1 is installed at the 3‐position. On the other hand, under basic conditions (pH 5–9), 3‐(methylthio)propenones 2 undergo intial nucleophilic attack by hydroxylamine at the carbonyl group to give only the regioisomeric isoxazoles (i.e., 6 ) after subsequent intramolecular cyclization via intermediates 9 – 11 (Scheme ) 17,18,26,27…”