Methanol → Methyl 3-{[(1,1-dimethylethyl)oxy]methyl}-5-(1-methylethyl)-4-isoxazolecarboxylate

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Reaction Steps

To a solution of (1,1-dimethylethyl)oxyethanal oxime (8.59 g, 65.5 mmol) in N,N-dimethylformamide (50 mL) was added N-chlorosuccinimide (8.45 g, 65.5 mmol). The solution was stirred for approximately 1 hour. The solution was poured into ether and washed twice with water. The organic layer containing the crude imidoyl chloride was then washed with brine, was dried over magnesium sulfate and concentrated. Then to a solution of methyl isobutyrylacetate (8.86 mL, 78.6 mmol) in tetrahydrofuran (40 mL) at 0° C. was added a 0.5 M solution of sodium methoxide in methanol (157 mL, 78.6 mmol). After stirring for approximately 5 minutes the above imidoyl chloride was added in tetrahydrofuran (30 mL). A solid was observed to precipitate. After the addition was complete the mixture was allowed to stir and warm to ambient temperature overnight. Then the solution was poured into ether and washed with water containing sodium chloride, dried over magnesium sulfate and concentrated to afford methyl 3-{[(1,1-dimethylethyl)oxy]methyl}-5-(1-methylethyl)-4-isoxazolecarboxylate (10.6 g, 63%). 1H-NMR (400 MHz, DMSO-d6) δ 4.52 (s, 2H), 3.77 (s, 3H), 3.67 (septet, J=7 Hz, 1H), 1.25 (d, J=7 Hz, 6H), 1.18 (s, 9H).

Provenance & Evidence