反应详情

In a 30 mL microwave reaction tube were combined 4-(trifluoromethoxy)phenyl-hydrazine hydrochloride (1062 mg, 5.0 mmol; Maybridge), 9-azabicyclo[3.3.1]nonan-3-one hydrochloride (878 mg, 5.0 mmol; Accela ChemBio), and 1 N HCl in acetic acid (15 mL, 15 mmol; Aldrich). The reaction mixture was microwaved at 150° C. (Biotage Personal Chemistry, maximum 300 W) for 15 minutes, then cooled to room temperature. The solvent was removed, and the residue was dissolved in water (20 mL) and basified with solid potassium carbonate to ˜pH 12. This solution was extracted with dichloromethane (3×50 mL), and the combined organic phases were dried over magnesium sulfate. After removing the solvent under vacuum, the residue was purified by flash chromatography (silica gel, CH2Cl2/CH3OH, 3:1) to afford the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.33-1.52 (m, 2H), 1.64-1.78 (m, 2H), 1.89-2.06 (m, 2H), 2.68 (d, J=17 Hz, 1H), 3.25-3.34 (m, 1H), 3.62 (t, J=5 Hz, 1H), 4.43 (t, J=3 Hz, 1H), 6.93 (ddd, J=9, 2, 1 Hz, 1H), 7.22 (d, J=1 Hz, 1H), 7.31 (d, J=9 Hz, 1H); MS (DCI/NH3) m/z 297 (M+H)+.

1. customIn a 30 mL microwave reaction tube were combined
2. customThe reaction mixture was microwaved at 150° C. (Biotage Personal Chemistry, maximum 300 W) for 15 minutes
3. customThe solvent was removed
4. dissolutionthe residue was dissolved in water (20 mL)
5. extractionThis solution was extracted with dichloromethane (3×50 mL)
6. dry with materialthe combined organic phases were dried over magnesium sulfate
7. customAfter removing the solvent under vacuum
8. customthe residue was purified by flash chromatography (silica gel, CH2Cl2/CH3OH, 3:1)