反应详情

温度

50 °C

A suspension of 5-bromo-4-methyl-3-(3-trifluoromethyl-phenyl)-pyridin-2-ylamine (Int. 1, 1.0 g, 3.02 mmol) in IPA (3 mL) was treated with dimethylformamide dimethyl acetal (522 μL, 3.93 mmol) then heated at reflux for 3 hrs. The reaction mixture was cooled to 50° C. and hydroxylamine hydrochloride (273 mg, 3.93 mmol) was added. The reaction mixture was stirred at 50° C. for 1.5 hrs then allowed to cool and the resultant precipitate was collected by filtration, washing with IMS. The solid thus obtained was dissolved in THF (10 mL) and cooled to 0° C. before dropwise addition of trifluoroacetic anhydride (481 μL, 3.46 mmol), keeping the internal temperature below 10° C. Once addition was complete the reaction mixture was stirred at room temperature for 18 hrs. Sodium hydrogen carbonate (5% solution, 25 mL) was added and the mixture was extracted with EtOAc (2×25 mL). The combined organic extracts were washed with 5% sodium hydrogen carbonate solution (15 mL), then dried (Na2SO4), filtered and concentrated in vacuo to give the title compound as a white solid (1.05 g).

1. temperaturethen heated
2. temperatureat reflux for 3 hrs
3. temperatureto cool
4. filtrationthe resultant precipitate was collected by filtration
5. washwashing with IMS
6. customThe solid thus obtained
7. customthe internal temperature below 10° C
8. additionOnce addition
9. stirringwas stirred at room temperature for 18 hrs
10. extractionthe mixture was extracted with EtOAc (2×25 mL)
11. washThe combined organic extracts were washed with 5% sodium hydrogen carbonate solution (15 mL)
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo