Toluene → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-isopropyl-nicotinamide

Participants

Reaction Conditions

Reaction Steps

A trimethylaluminium solution (2 M in toluene, 418 μL, 0.84 mmol) was added to a solution of isopropylamine (49.6 mg, 0.84 mmol) in dioxane (3.75 mL). 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (75.0 mg, 0.21 mmol) in dioxane (3.75 mL) was added after 1 h at 50° C. The reaction mixture was stirred at 85° C. overnight. Again trimethylaluminium solution in toluene (2 M, 418 μL, 0.84 mmol) and isopropylamine (49.6 mg, 0.84 mmol) was added and stirring was continued for 3 h at 85° C. The solvent was removed by distillation. The residue was purified by chromatography (silica, ethyl acetate:heptane=1:1 to 7:3) to afford the title compound (32 mg, 39%) as white solid. MS: m/e=386.2 [M+H]+.

Provenance & Evidence