反应详情

温度

0 °C

n-Butyllithium (2.5 M in hexanes, 13.8 mL, 34.4 mmol) was added slowly to a solution of diisopropylamine (4.53 mL, 32.3 mmol) in anhydrous THF (50 mL) at −78° C. After being stirred for 0.1 hour, the mixture was allowed to warm up to 0° C. Stirring continued for 0.5 hour. The mixture was then cooled to −78° C. and 2,6-lutidine (3.76 mL, 32.3 mmol) was added slowly. The mixture was allowed to warm up to 0° C. and stirred for 0.5 hour. The mixture was then cooled to −78° C. before the slow addition of benzo[1,3]dioxole-5-carboxylic acid methoxy-methyl-amide (4.5 g, 21.5 mmol; see Example 2 above) in anhydrous THF (10 mL). The mixture was stirred at −78° C. for 0.5 hour, at 0° C. for 0.5 hour, and at room temperature for 2 hours. The mixture was then quenched with ammonium chloride aqueous solution and extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate, filtered, and concentrated. After purification using column chromatography on silica gel (eluent: ethyl acetate (2): hexanes (8)), 4.8 g (87%) of 1-Benzo[1,3]dioxol-5-yl-2-(6-methyl-pyridin-2-yl)-ethanone as a yellow solid was obtained. MS (ESP+) m/z 256.1 (M+1). 1H NMR (400 MHz, Methanol-d4) δ 7.56 (t, 1H, J=7.5 Hz), 7.39 (dd, 1H, J=1.8 Hz, 8.3 Hz), 7.30 (dd, 1H, J=0.5 Hz, 1.8 Hz), 6.93 (m, 1H), 6.83 (m, 2H), 5.98 (s, 2H), 4.87 (s, 2H), 2.50 (s, 3H).

1. stirringStirring
2. waitcontinued for 0.5 hour
3. temperatureThe mixture was then cooled to −78° C.
4. temperatureto warm up to 0° C.
5. stirringstirred for 0.5 hour
6. stirringThe mixture was stirred at −78° C. for 0.5 hour, at 0° C. for 0.5 hour
7. waitat room temperature for 2 hours
8. customThe mixture was then quenched with ammonium chloride aqueous solution
9. extractionextracted with ethyl acetate
10. washThe extract was washed with brine
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customAfter purification