反应详情

温度

75 °C

Stir a mixture of hypophosphorous acid 50 wt. % aq. sol'n (0.555 g) and 5% Pt/C (2.5 g) in H2O (20 mL, 0.4 vol.) for 10 minutes. Add solid VO(acac)2 (0.420 g, 1.20 mmol) and stir the dark slurry for an additional 5 minutes. Charge this slurry to a mixture of 2-(2,2-dimethylpropylamino)-3-nitro-6-bromopyridine (50.00 g, 173.61 mmol) in toluene (500.00 mL) in a one liter autoclave at ambient temperature. Heat the autoclave to 75° C. in the presence of H2 at 35 psi (2.38 atmospheres) with stirring at 100 rpm. After 3 hours filter the reaction mixture over a Hyflo Super Cel® pad and concentrate the filtrate under reduced pressure to one half of the overall mass (273.0 g) of the solution. Stir the solution and add cyanogen bromide (18.4 g, 173.70 mmol) followed by MeOH (250 mL). After 18 h, heat to 40° C. and concentrate under reduced pressure until 350 mL of solvent is collected via short path distillation. Dilute the resulting slurry with MTBE (350 mL, 7.0 vol.), cool to 0° C., and stir 1 h. Filter off solid, wash with MTBE (75 ml, 1.5 vol.), and dry under reduced pressure at 40° C. for 24 h to provide 48.06 g (76%) of the desired compound as a white solid.

1. stirringstir the dark slurry for an additional 5 minutes
2. additionCharge this slurry
3. stirringwith stirring at 100 rpm
4. filtrationAfter 3 hours filter the reaction mixture over a Hyflo Super Cel® pad
5. concentrationconcentrate the filtrate under reduced pressure to one half of the overall mass (273.0 g) of the solution
6. stirringStir the solution
7. temperatureheat to 40° C.
8. concentrationconcentrate under reduced pressure until 350 mL of solvent
9. distillationis collected via short path distillation
10. additionDilute the resulting slurry with MTBE (350 mL, 7.0 vol.)
11. temperaturecool to 0° C.
12. stirringstir 1 h
13. filtrationFilter off solid
14. washwash with MTBE (75 ml, 1.5 vol.)
15. customdry under reduced pressure at 40° C. for 24 h