反应详情

Methyl 6-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]isothiazole-3-carboxylate (37 mg, 0.062 mg) in a 3:2:1 THF-MeOH—H2O solution (1 mL) was treated with a 6N LiOH solution (85 μL, 0.49 mmol) at rt for 12 hours. After this time the organic was removed in vacuo and the residue was diluted with water (1 mL.) and cooled in ice. 3N NaOH was added dropwise until pH 7. The solid that separated was collected by filtration, washed with additional water and dried in vacuo to afford the 6-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]isothiazole-3-carboxylic acid as off white solid. 1H NMR (400 MHz, DMSO) δ 8.31 (d, J=8.0 Hz, 1H), 7.68-7.62 (m, 2H), 7.57-7.52 (m, 2H), 7.18 (bs, 1H), 6.90 (d, J=9.2 Hz, 1H), 4.31 (s, 2H), 4.18 (bs, 2H), 3.42 (m, 1H), 1.88-1.84 (m, 2H), 1.80 (1.78 (m, 4H), 1.53-1.49 (m, 2H), 1.15-1.03 (m, 5H). MS m/z 586.2 (M+1).

1. customAfter this time the organic was removed in vacuo
2. additionthe residue was diluted with water (1 mL.)
3. temperaturecooled in ice
4. addition3N NaOH was added dropwise until pH 7
5. customThe solid that separated
6. filtrationwas collected by filtration
7. washwashed with additional water
8. customdried in vacuo