反应详情

温度

90 °C

To a stirred solution of 2-chloro-3-methyl-5-nitropyridine (prepared according to the procedure of Hawkins and Roe, J. Am. Chem. Soc., page 330, 1948) (5.3 g, 30.7 mmol, 1 eq.) in 1,2-dimethoxyethane (50 mL) and ethanol (25 mL) was added 2-chloro-4-fluorobenzeneboronic acid (5.9 g, 33.8 mmol, 1.1 eq.). The resulting mixture was degassed with argon. To the mixture was added a solution of Na2CO3 (11.4 g, 107.45 mmol, 3.5 eq) in water (50 mL). The mixture was degassed with argon, and tetrakis(triphenylphosphine)palladium(0) (1.1 g, 0.95 mmol, 0.03 eq) was added. The mixture was degassed with argon and heated to 90° C. under argon. After 4.5 h, the mixture was cooled. The solvent was removed under reduced pressure. The residue was diluted with water and extracted 3× with ethyl acetate. The aqueous layer was extracted several times with ethyl acetate. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated. The product was purified by flash column chromatography on silica gel eluting with 5% Et2O in hexanes giving 2-(2-chloro-4-fluorophenyl)-3-methyl-5-nitropyridine. Mass spectrum (EST) 267 (M+1).

1. customThe resulting mixture was degassed with argon
2. additionwas added
3. customThe mixture was degassed with argon
4. temperaturethe mixture was cooled
5. customThe solvent was removed under reduced pressure
6. additionThe residue was diluted with water
7. extractionextracted 3× with ethyl acetate
8. extractionThe aqueous layer was extracted several times with ethyl acetate
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe product was purified by flash column chromatography on silica gel eluting with 5% Et2O in hexanes