Methyl 5-isopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate synthesis

Yield:1097776-52-7 67%

Reaction Conditions:

Stage #1: Methyl 4-methyl-3-oxopentanoatewith sodium hydroxide in methanol at 0;
Stage #2: (Z)-N-hydroxy-2-(trifluoromethoxy)benzimidoyl chloride in tetrahydrofuran;methanol at 20;

Steps:

7.c

A 0.5 M solution of sodium hydroxide in methanol (10.5 mL) was added drop wise to a 0 ⁰C solution of methyl isobutyryl acetate (0.75 mL, 5.27 mmol) in tetrahydrofuran (2 mL). After 5 minutes of stirring, a solution of /V-hy droxy-2 - [(trifluoromethyl)oxy]benzene- carboximidoyl chloride (0.93 g, 3.88 mmol) in tetrahydrofuran (5 mL) was added. The mixture was stirred at room temperature overnight. The mixture was concentrated. Water was added, and the resulting precipitate was filtered and dried under high vacuum to give 1.07 g (67%) of methyl 5-(l-methylethyl)-3-{2- [(trifluoromethyl)oxy]phenyl}-4-isoxazolecarboxylate as a solid. ¹H NMR (400 MHz, CDCl₃): δ 7.54-7.49 (m, 2H), 7.39-7.31 (m, 2H), 3.85-3.75 (m, IH), 3.67 (s, 3H), 1.40 (d, J = 7 Hz, 6H).

References:

WO2009/5998,2009,A1 Location in patent:Page/Page column 102-103