Hydrochloric Acid → 3-(6-Methylpyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acid

Participants

Reaction Steps

To a mixture of N-hydroxy-6-methylpicolinimidoyl chloride (2.5 g, 14.65 mmol) and (Z)-ethyl 2-bromo-4,4,4-trifluorobut-2-enoate, Int-I-F (3 g, 12.15 mmol) in ethyl acetate (40 mL) was added indium(III) chloride (0.559 g, 2.53 mmol). After 1 hour, potassium hydrogen carbonate (2.022 g, 20.20 mmol) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate (40 mL) and washed with H2O. The organic layer was dried with MgSO4, filtered, and concentrated. The resulting material was purified on a silica gel cartridge using an EtOAc/hexanes gradient. The fraction with desired mass was isolated and checked by NMR. The product was found to be contaminated with dimerization product of the starting bromoolefin. This material was hydrolyzed using 1N LiOH (2eq) in EtOH for 1 hour. The pH was adjusted to 6-7 with concentrated HCl. The resulting material was extract with EtOAc 4 times and then extracts were combined, dried, and concentrated to yield 360 mg of 3-(6-methylpyridin-2-yl)-4-(trifluoromethyl)isoxazole-5-carboxylic acid. MS (m+1)=273. HPLC Peak RT=1.66 minutes (Analytical Method B).

Provenance & Evidence