反应详情

温度

60 °C

To a solution of 4-cyclopropyl-2-fluoro-6-methylbenzamide (37.2 g, 0.19 mol) in 2-methyltetrahydrofuran (MeTHF; 223 ml) was added 1,1-dimethoxy-N,N-dimethylmethanamine (29.8 g, 0.25 mol). The mixture was heated to 60° C. for 2 hours, then around 100 mL of MeTHF was distilled out under vacuum in order to remove Methanol. The reaction mixture was heated to 55° C. again, and potassium tert-butoxide, 1 M solution in THF (289 ml, 0.29 mol) was added dropwise. After 1 hr stirring at 60° C., the reaction mixture was allowed to cool down to room temperature and poured into HCl, 1 M solution (289 ml, 0.29 mol), and then THF/MeTHF was distilled out at 60° C. for crystallization. During the distillation, IPA (223 ml) was added slowly. After most of THF/MeTHF was removed, the solution was cooled down to ambient temperature. The desired product was crystallized out from IPA/water, collected by filtration and washed with water and cold IPA. The filter cake was dried under vacuum at 50° C. to afford 30.1 g of the title compound (77% isolated yield) as a white solid. MS (ESI) 204 (M+H)+.

1. distillationaround 100 mL of MeTHF was distilled out under vacuum in order
2. customto remove Methanol
3. temperatureThe reaction mixture was heated to 55° C. again
4. temperatureto cool down to room temperature
5. distillationTHF/MeTHF was distilled out at 60° C. for crystallization
6. distillationDuring the distillation, IPA (223 ml)
7. additionwas added slowly
8. customAfter most of THF/MeTHF was removed
9. temperaturethe solution was cooled down to ambient temperature
10. customThe desired product was crystallized out from IPA/water
11. filtrationcollected by filtration
12. washwashed with water and cold IPA
13. customThe filter cake was dried under vacuum at 50° C.