Ethyl Acetate → 2,4-Dimethyl-5-nitropyridine

To a stirred suspension of 2-chloro-4-methyl-5-nitropyridine (9.419 g, 54.6 mmol) in dioxane (110 mL) was added tetrakis(triphenyl phosphine) palladium (6.330 g, 5.46 mmol) and the mixture stirred for 15 min prior to the addition of trimethyl boroxine (7.68 mL, 54.6 mmol) and potassium carbonate (22.64 g, 164.0 mmol). The reaction mixture was heated under reflux for 6 h then allowed to cool to rt over 16 h. Ethyl acetate (200 mL) was added and the mixture stirred vigorously for 1 h. The mixture was filtered through celite, washing through with ethyl acetate/THF (1:1, v/v). Brine (100 mL) was added and attempted separation of layers resulted in a thick emulsion. After removal of all volatiles, ethyl acetate (300 mL) was added and the mixture filtered, giving rise to a biphasic mixture. The layers were separated and the aqueous phase was extracted with ethyl acetate (3×100 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting oil was dissolved in dichloromethane then purified via flash column chromatography (SiO2, ethyl acetate/isohexane, 3:7, v/v) to give the title compound as an orange oil. δH (CDCl3): 2.59 (3H, s), 2.60 (3H, s), 7.12 (1H, s), 9.07 (1H, s).

1. temperatureThe reaction mixture was heated
2. temperatureunder reflux for 6 h
3. stirringthe mixture stirred vigorously for 1 h
4. filtrationThe mixture was filtered through celite
5. washwashing through with ethyl acetate/THF (1:1
6. additionBrine (100 mL) was added
7. customseparation of layers
8. customresulted in a thick emulsion
9. customAfter removal of all volatiles, ethyl acetate (300 mL)
10. additionwas added
11. filtrationthe mixture filtered
12. customgiving rise to a biphasic mixture
13. customThe layers were separated
14. extractionthe aqueous phase was extracted with ethyl acetate (3×100 mL)
15. washThe combined organics were washed with brine (100 mL)
16. dry with materialdried (MgSO4)
17. filtrationfiltered
18. concentrationconcentrated in vacuo
19. dissolutionThe resulting oil was dissolved in dichloromethane
20. customthen purified via flash column chromatography (SiO2, ethyl acetate/isohexane, 3:7, v/v)

ORD record

ord-508c9672e15d4b2f898ea9ffb38b7053

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07405210B2