反应详情

Add 6-chloronicotinamide (7.03 g, 44.90 mmol) to a stirred solution of 4-(2-benzylamino-ethyl)-phenol (10.10 g, 44.43 mmol), potassium carbonate (15.35 g, 111.1 mmol), dimethylacetamide (138 mL), and isooctane (16 mL). Using a Dean-Stark trap, heat the reaction to reflux under nitrogen for 6 h. Cool the reaction mixtures to room temperature, filter off the solids, and concentrate most of the solvent off on a rotary evaporator. Take the residue up in ethyl acetate (200 mL) and add 1N hydrochloric acid (200 mL). Stir for 15 minutes and filter off the precipitate washing with ethyl acetate. Dissolve the solid in 400 mL of boiling 1:1 methanol/water. To this solution add 5N sodium hydroxide (35 mL) and allow the solution to cool to room temperature. Filter and wash with water to yield 19.74 g (83%) of 6-[4-(2-benzylamino-ethyl)-phenoxy]-nicotinamide: mass spectrum (ion spray): m/z=348.1 (M+1); 1H NMR (CDCl3): 8.58 (d, 1H), 8.15 (dd, 1H), 7.34-7.24 (m, 7H), 7.06 (d, 2H), 6.93 (d, 1H), 6.08 (br s, 2H), 3.82 (s, 2H), 2.92 (t, 2H), 2.84 (t, 2H), 1.33 (br s, 1H).

1. temperatureheat
2. customthe reaction
3. temperatureto reflux under nitrogen for 6 h
4. temperatureCool the reaction
5. custommixtures to room temperature
6. filtrationfilter off the solids
7. concentrationconcentrate most of the solvent off on a rotary evaporator
8. additionadd 1N hydrochloric acid (200 mL)
9. filtrationfilter off the precipitate
10. washwashing with ethyl acetate
11. dissolutionDissolve the solid in 400 mL
12. additionTo this solution add 5N sodium hydroxide (35 mL)
13. filtrationFilter
14. washwash with water