反应详情

温度

70 °C

To a 25-mL round-bottom flask equipped with a stir bar was added sequentially methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-fluorobenzo[d]thiazole-6-carboxylate (0.55 g, 0.89 mmol), 4.0 mL of THF, 2.0 mL of MeOH, and 3 N aqueous KOH solution (1 mL, 3 mmol). The resulting homogenous solution was stirred for 1 hour at 70° C., cooled to RT, and then quenched with AcOH (roughly 0.2 mL of glacial acetic, 3 mmoles) until pH=6 was achieved (Whatman class pH strip paper). At this time the reaction was diluted with ethyl acetate (40 mL) and washed with water (3×5 mL). The ethyl acetate fraction was concentrated under vacuum to give to an oily residue. To the resulting oil was then added 6 mL of MeOH. The oil quickly dissolved, then immediately began to crystallize. Upon standing for 2.5 hrs the mother liquor was withdrawn and crystals washed (3×2 mL of ice cold MeOH). The crystals were dried via vacuum (10 mm Hg pressure at 45° C. overnight) and then recrystallized from acetonitrile, filtered, and dried under vacuum to give the desired product 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-fluorobenzo[d]thiazole-6-carboxylic acid.

1. customTo a 25-mL round-bottom flask equipped with a stir bar
2. temperaturecooled to RT
3. washwashed with water (3×5 mL)
4. concentrationThe ethyl acetate fraction was concentrated under vacuum
5. customto give to an oily residue
6. dissolutionThe oil quickly dissolved
7. customto crystallize
8. waitUpon standing for 2.5 hrs
9. customthe mother liquor was withdrawn
10. washcrystals washed (3×2 mL of ice cold MeOH)
11. customThe crystals were dried via vacuum (10 mm Hg pressure at 45° C. overnight)
12. customrecrystallized from acetonitrile
13. filtrationfiltered
14. customdried under vacuum