反应详情

温度

-15 °C

3.3 ml (26.6 mmol) of boron trifluoride diethylether complex were cooled to −15° C. Then 2.5 g (13.3 mmol) of 6-(2-fluoro-phenyl)-pyridin-3-ylamine in 5 ml of DME and, subsequently, 1.9 ml (15.9 mmol) of tert-butyl nitrite were added dropwise. Shortly after, a thick precipitate formed. The mixture was diluted with 8 ml of DME and 8 ml of dichloromethane and stirred in an ice bath for 2 h. After addition of 50 ml of pentane, the precipitate was filtered off, dried, and stirred in 50 ml of acetic anhydride at 100° C. for 1 h. After concentration, a sodium hydrogencarbonate solution was added, and the mixture was extracted with ethyl acetate. The combined organic phases were dried and evaporated. The residue was purified by chromatography (silica gel, n-heptane/ethyl acetate 5:1). The obtained product was stirred with a 15% aqueous potassium hydroxide solution and few methanol in an ice bath and subsequently for 2 h at room temperature. After neutralization with 2 N hydrochloric acid, the mixture was extracted with ethyl acetate, and the combined extracts were dried and evaporated. Yield: 871 mg.

1. customShortly after, a thick precipitate formed
2. filtrationthe precipitate was filtered off
3. customdried
4. stirringstirred in 50 ml of acetic anhydride at 100° C. for 1 h
5. concentrationAfter concentration
6. additiona sodium hydrogencarbonate solution was added
7. extractionthe mixture was extracted with ethyl acetate
8. customThe combined organic phases were dried
9. customevaporated
10. customThe residue was purified by chromatography (silica gel, n-heptane/ethyl acetate 5:1)
11. stirringThe obtained product was stirred with a 15% aqueous potassium hydroxide solution and few methanol in an ice bath and subsequently for 2 h at room temperature
12. extractionAfter neutralization with 2 N hydrochloric acid, the mixture was extracted with ethyl acetate
13. customthe combined extracts were dried
14. customevaporated