反应详情

温度

150 °C

To a solution of 2-amino-4-chloropyridine (2.0 g, 15.6 mmol) in N-methylpyrrolidone (16 ml) were added 5-hydroxy-2-nitrobenzotrifluoride (4.85 g, 23.4 mmol) and diisopropylethylamine (8.15 ml, 46.8 mmol), followed by stirring under a nitrogen atmosphere to heat at 150° C. for 62 hrs. The reaction mixture was cooled down to room temperature and the diisopropylethylamine was evaporated under a reduced pressure. The resultant residue was partitioned between ethyl acetate:tetrahydrofuran=1:1 (300 ml) and a 1 N aqueous solution of sodium hydroxide (100 ml). The organic layer was washed with a 1 N aqueous solution of sodium hydroxide and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; heptane/ethyl acetate=1/2, ethyl acetate, then ethyl acetate/methanol=20/1). The crude product was subjected to silica gel filtration (Fuji Silysia NH) The filtrate was concentrated to give a solid, which was then suspended in diethyl ether:hexane=1:1, filtered, and dried under aeration to provide the titled compound (760 mg, 16.3%) as a brown solid.

1. temperatureThe reaction mixture was cooled down to room temperature
2. customthe diisopropylethylamine was evaporated under a reduced pressure
3. customThe resultant residue was partitioned between ethyl acetate
4. washThe organic layer was washed with a 1 N aqueous solution of sodium hydroxide and brine in this order
5. dry with materialdried over anhydrous sodium sulfate
6. customThe solvent was evaporated
7. customto give a residue, which
8. customwas then purified by silica gel column chromatography (eluent
9. filtrationThe crude product was subjected to silica gel filtration (Fuji Silysia NH) The filtrate
10. concentrationwas concentrated
11. customto give a solid, which
12. filtrationhexane=1:1, filtered
13. customdried under aeration