反应详情

温度

80 °C

A 50 mL round bottomed flask was charged with of ethyl 3-(dimethylamino)-2-(3-fluoro-4-nitrobenzoyl)acrylate (51.74 g, 166.75 mmol) and 2-aminomalonamide (23.4 mg, 200 mmol) and AcOH (1 L). The reaction mixture was heated to 80° C. over night. The starting material appeared consumed by TLC. The AcOH was removed under reduced pressure and TFA (300 mL) was added. The mixture was heated over night at 60° C. The reaction was cooled to room temperature and the TFA was removed under reduced pressure. The orange oil was treated with saturated aqueous NaHCO3 (1 L), then solid NaHCO3 was added until the solution was neutral. The solids were filtered and placed in a 1 L erlenmeyer flask. The solids were washed with H2O (3×1 L) and the water was decanted off through the filter. On the last washing the solids were poured onto the filter and allowed to air dry. The solids were once again removed from the filter and washed with Et2O (4×500 mL). The Et2O was decanted off through the filter and on the final washing the solids were transferred to the filter. An addition portion of Et2O (200 mL) was used to wash the flask and the filter cake. The desired product was dried in a vacuum oven at 40° C. to provide a light tan solid (36.8 g, 114.5 mmol, 69% yield). 1H-NMR (DMSO-d6) δ 12.28 (br s, 1H), 8.07 (app t, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.46 (dd, J=12.6, 1.6 Hz, 1H), 7.28 (dd, J=8.4, 1.6 Hz, 1H), 7.25 (br s, 1H), 6.72 (br s, 1H), 4.01 (q, J=7.2 Hz, 2H), 1.07 (t, J=7.2 Hz, 3H); LCMS*RT=4.45 min; MS {M−H]−=320.1.

1. customThe starting material appeared consumed by TLC
2. customThe AcOH was removed under reduced pressure and TFA (300 mL)
3. additionwas added
4. temperatureThe mixture was heated over night at 60° C
5. temperatureThe reaction was cooled to room temperature
6. customthe TFA was removed under reduced pressure
7. additionThe orange oil was treated with saturated aqueous NaHCO3 (1 L)
8. additionsolid NaHCO3 was added until the solution
9. filtrationThe solids were filtered
10. customplaced in a 1 L erlenmeyer flask
11. washThe solids were washed with H2O (3×1 L)
12. customthe water was decanted off through the filter
13. washOn the last washing the solids
14. additionwere poured onto the
15. filtrationfilter
16. customto air dry
17. customThe solids were once again removed from the
18. filtrationfilter
19. washwashed with Et2O (4×500 mL)
20. customThe Et2O was decanted off through the
21. filtrationfilter
22. washon the final washing the solids
23. washto wash the flask
24. dry with materialThe desired product was dried in a vacuum oven at 40° C.