反应详情

温度

100 °C

Aqueous sodium hydroxide (50%, 2.08 g, 25.5 mmol) was added dropwise to a stirred solution of hydroxylamine sulfate (1.07 g, 6.52 mmol) in water (20 mL) at 25° C. After this addition was complete the product of Example 8, Step A (5 g, 10.27 mmol) in tetrahydrofuran (20 mL) was added dropwise over 40 min. After the addition was complete the mixture was stirred further for 30 min. The organic phase was separated and added to hydrochloric acid (100 mL). The mixture was extracted with ethyl acetate (2×20 mL). The organic solvent was evaporated under reduced pressure. The residue was redissolved in acetic acid (16 mL) and then warmed to 100° C. Water (2 mL) was added dropwise, and the mixture was cooled to 50° C. The mixture was seeded with a small amount of previously prepared methyl 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-1-naphthalenecarboxylate and then cooled to 25° C. Water (2 mL) was added and the mixture was cooled to 0° C. The mixture was filtered, and the solid was washed with acetic acid:water (8 mL:2 mL). The solid was dried in a vacuum oven to give the title product as a white solid (3.91 g, 76% yield) melting at 111.5-112° C. (after recrystallisation from acetonitrile).

1. additionAfter this addition
2. additionwas added dropwise over 40 min
3. additionAfter the addition
4. customThe organic phase was separated
5. additionadded to hydrochloric acid (100 mL)
6. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
7. customThe organic solvent was evaporated under reduced pressure
8. dissolutionThe residue was redissolved in acetic acid (16 mL)
9. additionWater (2 mL) was added dropwise
10. temperaturethe mixture was cooled to 50° C
11. temperaturecooled to 25° C
12. additionWater (2 mL) was added
13. temperaturethe mixture was cooled to 0° C
14. filtrationThe mixture was filtered
15. washthe solid was washed with acetic acid
16. customThe solid was dried in a vacuum oven