反应详情

温度

60 °C

A mixture of ethyl 5-amino-4-methylpyridine-2-carboxylate (2.58 g), iodine (2.91 g) and sodium periodate (1.22 g) in N,N-dimethylformamide (20 mL) was stirred at 60° C. for 6 days. The reaction mixture was cooled to room temperature. To the reaction mixture was added 1 mol/L aqueous sodium thiosulfate solution, and the resulting mixture was extracted with ethyl acetate twice. The extracts were washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1−1/1) to give ethyl 5-amino-6-iodo-4-methylpyridine-2-carboxylate (2.31 g). To sodium hexamethyldisilazide (1.03 mol/L tetrahydrofuran solution, 10.5 mL) was added a solution of ethyl 5-amino-6-iodo-4-methylpyridine-2-carboxylate (1.51 g) in tetrahydrofuran (9 mL) in a dropwise manner at −10° C., and the mixture was stirred at the same temperature for 10 minutes. To the mixture was added a solution of di(tert-butyl)dicarbonate (1.18 g) in tetrahydrofuran (4 mL) in a dropwise manner, and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1−2/1) to give the title compound (1.11 g).

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionthe resulting mixture was extracted with ethyl acetate twice
3. washThe extracts were washed with water and brine
4. dry with materialdried over anhydrous magnesium sulfate
5. customThe solvent was removed under reduced pressure
6. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1−1/1)