反应详情

Sodium hydride (25.6 g, 60% dispersion in oil, 0.64 mol) was added portion-wise to a solution of 5-hydroxy-2-methylpyridine (70 g, 0.64 mol) in DMA (700 ml) while keeping the temperature below 40° C. At the end of the addition, the mixture was stirred at room temperature for 1 hour and 2-fluoro-5-nitrotoluene (91.3 g, 0.59 mol) in DMA (100 ml) was added slowly. The mixture was stirred at 80° C. for 3 hours and then cooled. The solvents were evaporated under vacuum and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over MgSO4. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 30% ethyl acetate in petroleum ether) to give 2-methyl-5-(2-methyl-4-nitrophenoxy)pyridine as an oil (141 g, 98%); NMR spectrum (CDCl3): 2.43 (s, 3H), 2.59 (s, 3H), 6.74 (d, 1H), 7.21 (d, 1H), 7.27 (d, 1H), 8.00 (d, 1H), 8.17 (s, 1H), 8.32 (s, 1H).

1. customthe temperature below 40° C
2. additionAt the end of the addition
3. stirringThe mixture was stirred at 80° C. for 3 hours
4. temperaturecooled
5. customThe solvents were evaporated under vacuum
6. customthe residue was partitioned between ethyl acetate and water
7. washThe organic layer was washed with water and brine
8. dry with materialdried over MgSO4
9. customAfter evaporation of the solvents
10. customthe residue was purified by chromatography on silica gel (eluant: 30% ethyl acetate in petroleum ether)