反应详情

温度

40 °C

Add 1-azidomethyl-3,5-bistrifluoromethylbenzene (3.73 g, 13.8 mmol) and potassium carbonate (5.73 g, 41.4 mmol) to a solution of (2-chlorophenyl)-[2-(2-hydroxy-2-pyridin-4-yl-vinyl)pyridin-3-yl]methanone phosphate (6.0 g, 13.8 mmol) in DMSO (16 mL). Heat to 40° C. and stir for approximately 20-24 h. Cool the reaction mixture to ambient temperature, and add the mixture to CH2Cl2 (75 mL) and 1 N NaOH (75 mL). Separate the layers, and extract the aqueous layer with CH2Cl2 (50 mL). Separate the layers, combine the organic layers and extract the combined organic layers with 1 N NaOH (2×50 mL). Add MgSO4 and acid-washed carbon (1.2 g), stir for 20 min and filter through Celite®. Concentrate the filtrate to a total weight of approximately 25 g. Add heptane (75 mL) dropwise over approximately 45 min. Seed the solution with the title compound if necessary. Stir the resulting slurry for 1 h and then filter to obtain the title compound. Dry the title compound, then add it to isopropanol (36 mL). Heat the mixture until the solid dissolves (approx. 65° C.). Allow the solution to cool to ambient temperature. Stir the resulting slurry for approximately 3 hours. Cool the slurry in an ice/water bath and stir for 2 h. Filter and dry to afford the title compound as a white solid. MS(IS) 588 (M+1). TLC (3% MeOH/CH2Cl2) Rf=0.17. 1H NMR (400 MHz, CDCl3): 5.46 (s, 2H); 7.19 (m, 5H); 7.36 (dd, 1H, J=4.9, 7.8); 7.45 (s, 2H); 7.59 (m, 1H); 7.83 (s, 1H); 7.93 (dd, 1H, J=1.5, 7.8); 8.56 (dd, 1H, J=1.5, 4.9); 8.70 (d, 2H, J=5.9).

1. temperatureCool the reaction mixture to ambient temperature
2. customSeparate the layers
3. extractionextract the aqueous layer with CH2Cl2 (50 mL)
4. customSeparate the layers
5. extractionextract the combined organic layers with 1 N NaOH (2×50 mL)
6. washAdd MgSO4 and acid-washed carbon (1.2 g)
7. stirringstir for 20 min
8. filtrationfilter through Celite®
9. concentrationConcentrate the filtrate to a total weight of approximately 25 g
10. waitAdd heptane (75 mL) dropwise over approximately 45 min
11. stirringStir the resulting slurry for 1 h
12. filtrationfilter