反应详情

温度

60 °C

Intermediate (23t) (1.78 g, 13.0 mmol), 2-chloro-4-methyl-5-nitropyridine (2.31 g, 13.0 mmol) and potassium carbonate (1.80 g, 13.0 mmol) were dissolved in DMF (120 mL). When the mixture was warmed to 60° C., the colorless solution turned blue in 10 minutes. After 16 hours of stirring at 60° C., the reaction mixture was allowed to cool down to room temperature and then diluted with 100 mL of Et2O. The inorganic precipitate was removed by filtration and washed with Et2O. The combined organic solution (600 mL total) was transferred to a separatory funnel and washed with 60 mL of water three times and with brine one time. The solution was dried over MgSO4 and then concentrated under reduced pressure to obtain crude brown solid. The crude solid was dissolved in MeOH (240 mL). To the solution was added 10% palladium on activated carbon under nitrogen atmosphere. Replacing nitrogen gas with hydrogen gas, the reaction mixture was stirred at room temperature (if the reaction did not proceed in 30 minutes, filtrated the Pd/C was filtered off and the reaction was set up again. After 1.5 hours of stirring, palladium on carbon was filtered off and washed with MeOH. The solution was concentrated under reduced pressure to obtain a pale yellow solid. The crude compound was purified on silica gel with EtOAc/hexane (1/1-3/2) to afford (1u) as a white solid (2.21 g, 70% yield over 2 steps). 1H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.33 (ddd, J=7.8, 3.1, 1.6 Hz, 1H), 7.29-7.22 (m, 1H), 7.23 (s, OH), 7.15 (ddd, J=9.3, 4.7, 1.6 Hz, 1H), 6.82 (s, 1H), 2.22 (s, 3H) ppm.

1. temperatureto cool down to room temperature
2. customThe inorganic precipitate was removed by filtration
3. washwashed with Et2O
4. customThe combined organic solution (600 mL total) was transferred to a separatory funnel
5. washwashed with 60 mL of water three times and with brine one time
6. dry with materialThe solution was dried over MgSO4
7. concentrationconcentrated under reduced pressure
8. customto obtain crude brown solid
9. waitdid not proceed in 30 minutes
10. filtrationfiltrated the Pd/C
11. filtrationwas filtered off
12. stirringAfter 1.5 hours of stirring
13. filtrationpalladium on carbon was filtered off
14. washwashed with MeOH
15. concentrationThe solution was concentrated under reduced pressure
16. customto obtain a pale yellow solid
17. customThe crude compound was purified on silica gel with EtOAc/hexane (1/1-3/2)