反应详情

温度

-10 °C

C9 (4.0 g, 21 mmol) and glycinamide acetate (2.79 g, 20.8 mmol) were dissolved in methanol (40 mL) and cooled to −10° C. Aqueous sodium hydroxide solution (12 N, 3.5 mL, 42 mmol) was added, and the resulting mixture was slowly warmed to room temperature. After stirring for 3 days, the reaction mixture was concentrated in vacuo. The residue was diluted with water, and 1 N aqueous hydrochloric acid was added until the pH was approximately 7. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was slurried with 3:1 ethyl acetate/heptane, stirred for 5 minutes, filtered, and concentrated in vacuo. Silica gel chromatography (Eluent: ethyl acetate) provided the product as a tan solid that contained 15% of an undesired regioisomer; this material was used without further purification. Yield: 2.0 g. LCMS m/z 231.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.14 (d, J=8.2 Hz, 1H), 6.82-6.87 (m, 2H), 3.86 (s, 3H), 2.20 (s, 3H), 2.11 (s, 3H).

1. temperaturethe resulting mixture was slowly warmed to room temperature
2. concentrationthe reaction mixture was concentrated in vacuo
3. additionThe residue was diluted with water, and 1 N aqueous hydrochloric acid
4. additionwas added until the pH was approximately 7
5. extractionThe aqueous phase was extracted with ethyl acetate
6. washthe combined organic extracts were washed with saturated aqueous sodium chloride solution
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. stirringstirred for 5 minutes
11. filtrationfiltered
12. concentrationconcentrated in vacuo