反应详情

温度

41.70000076293945 °C

4-(4-Methylamino-3-nitro-phenoxy)-pyridine-2-carbonitrile (5.0 g, 0.019 moles) in EtOH (15 mL) was heated to 40° C. Na2CO3 (4.7 g, 0.044 moles) was added followed by H2O (8.4 mL). Na2S2O4 (3.3 g, 0.019 moles) was added followed by H2O (10 mL). The temperature rose from 41.7 to 49.5° C. After cooling down to 41.7° C., Na2S2O4 (3.3 g, 0.019 moles) was added followed by H2O (10 mL). The temperature rose to 44.5° C. After cooling down to 36.7° C., Na2S2O4 (6.6 g, 0.038 moles) was added followed by H2O (20 mL). The temperature rose to 44.0° C. HPLC analysis showed 4.1% (LCAP) of the starting material. Additional Na2S2O4 (3.3 g, 0.019 moles) was added. After stirring an additional 15 min, heat was removed and H2O (12.5 mL) was added. At 25° C., additional Na2CO3 (1.3 g, 0.012 moles) was added and the mixture cooled in an ice/water bath. At less than 5° C., the mixture was allowed to age for 30 min (final temperature of 1.5° C.). The solid was collected by filtration and washed with H2O (10 mL followed by 5 mL). The solid was dried on the filter for 30 min and then transferred to the reaction flask and H2O (50 mL) added. The mixture was stirred for 45 min. The solid was then collected by filtration and washed with H2O (2×10 mL). The crude product was dried in a vacuum oven at 50° C. for 16 h to afford 3.50 g (76%) of the title compound: 1H NMR (400 MHz, DMSO-d6) δ 8.5 (m, 1H), 7.5 (m, 1H), 7.1 (m, 1H), 6.4 (m, 1H), 6.3 (m, 2H), 4.8 (s, 2H), 4.7 (s, 1H), 2.7 (s, 3H); APCI MS [M+H]=241; HPLC>99% (LCAP).

1. customrose from 41.7 to 49.5° C
2. customrose to 44.5° C
3. temperatureAfter cooling down to 36.7° C.
4. customrose to 44.0° C
5. temperatureheat
6. customwas removed
7. additionH2O (12.5 mL) was added
8. temperaturethe mixture cooled in an ice/water bath
9. waitAt less than 5° C., the mixture was allowed to age for 30 min
10. customtemperature of 1.5° C.
11. filtrationThe solid was collected by filtration
12. washwashed with H2O (10 mL followed by 5 mL)
13. customThe solid was dried on the
14. filtrationfilter for 30 min
15. additionadded
16. stirringThe mixture was stirred for 45 min
17. filtrationThe solid was then collected by filtration
18. washwashed with H2O (2×10 mL)
19. dry with materialThe crude product was dried in a vacuum oven at 50° C. for 16 h