Methanol → Methyl 2-(3-methylisoxazol-5-yl)acetate

Participants

Reaction Steps

A solution of 3-methyl-5-isoxazole acetic acid (10.2 g, 72.6 mmol) in methanol (100 mL) was treated with p-toluene-4-sulfonic acid monohydrate (1.0 g, cat.) and the resulting mixture was then heated under reflux for 4 h. After cooling, the mixture was then evaporated and the brownish residue stirred with saturated sodium bicarbonate solution and diethylether. The organic phase was dried over sodium sulfate and concentrated to afford (3-methyl-isoxazol-5-yl)-acetic acid methyl ester (9.62 g) as a light yellow oil. This was then dissolved in butanol and reacted with hydrazine hydrate As described for example 112a. The resulting mixture was then heated under reflux for 16 h and after cooling and evaporation, the residue was crystallized from n-butanol/toluene to afford the title compound as a white solid (5.30 g). Concentration of the mother liquor provided another crop of solid material (2.95 g, overall yield: 73%). 1H-NMR (300 MHz, DMSO): δ=2.19 (s, 3H), 3.25 (s, 2H), 4.29 (s, 2H), 6.17 (s, 1H), 9.29 (s, 1H).

Provenance & Evidence