反应详情

温度

0 °C

Sodium hydride (6.63 g of 60%, 166 mmol) was added to chilled (0° C.) anhydrous tetrahydrofuran (200 mL) and the mixture was allowed to stir for 15 minutes. A solution of phenol (15.07 g, 160 mmol) in tetrahydrofuran (150 mL) was added dropwise over a period of 1 hour. A solution of 5-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]pentan-1-ol (31.723 g, 110 mmol) in tetrahydrofuran (150 mL) was added dropwise over a period of 30 minutes while maintaining the reaction temperature at 0° C. The reaction mixture was allowed to warm to ambient temperature and then it was heated at reflux overnight. Analysis by thin layer chromatography indicated that the reaction was 50–60% complete. An additional equivalent of phenoxide was prepared and added to the reaction mixture at ambient temperature; then the reaction mixture was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (300 mL); washed sequentially with water (2×50 mL), 5% sodium hydroxide (2×50 mL)) and 1N sodium hydroxide (2×50 mL); dried over magnesium sulfate and then concentrated under reduced pressure. The residue was divided into two portions and purified by column chromatography (450 g of silica gel eluting with 1:1 hexanes:ethyl acetate to 1:3 hexanes:ethyl acetate) to provide 38.13 g of 5-[(2,3-dimethyl-5-nitro-6-phenoxypyridin-4-yl)amino]pentan-1-ol.

1. temperatureto warm to ambient temperature
2. temperatureit was heated
3. temperatureat reflux overnight
4. additionadded to the reaction mixture at ambient temperature
5. temperaturethen the reaction mixture was heated
6. temperatureat reflux overnight
7. concentrationThe reaction mixture was concentrated under reduced pressure
8. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
9. washwashed sequentially with water (2×50 mL), 5% sodium hydroxide (2×50 mL)) and 1N sodium hydroxide (2×50 mL)
10. dry with materialdried over magnesium sulfate
11. concentrationconcentrated under reduced pressure
12. custompurified by column chromatography (450 g of silica gel eluting with 1:1 hexanes:ethyl acetate to 1:3 hexanes:ethyl acetate)