Isopropanol → 6-Fluoro-3-(4-methoxyphenyl)-1,2-benzisoxazole

Participants

Reaction Steps

Combine (2,4-difluoro-phenyl)-(4-methoxy-phenyl)-methanone oxime (277.5 g, 1.05 mol), water (200 mL) and isopropyl alcohol (1140 mL) and heat (˜75-80° C.) under a nitrogen atmosphere. Add 45% potassium hydroxide (591.5 g), in one portion, followed by water (75 mL). Immediate exotherm to 82° C. Continue heating for 5.3 hours. Cool reaction mixture to room temperature overnight. Cool reaction mixture in an ice bath, filter and wash (2×250 mL) filter cake with a cold mixture of isopropyl alcohol and water (20:80). Let filter cake dry to the air to give the title compound (182.7 g, 73% Yield): 1H NMR (CDCl3, 200 MHz) δ 3.9 (s, 3H), 7.1 (m, 3H), 7.3 (m, 1H), 7.85 (m, 3H). Purity by LC/MS (APCl)=100% area, [M+H]+=244 m/e.

Provenance & Evidence