反应详情

温度

0 °C

A solution of 5.0 g (25.3 mmol) of 7-chloro-6-fluoro-isoquinoline 2-oxide (9) in 120 mL of benzotrifluoride was treated with 15.9 mL (11.1 g, 152 mmol) of tert-butylamine and cooled to 0° C. Then, 17.3 g (53.1 mmol) of p-toluenesulfonic anhydride were slowly added portionwise with temperature control (<10° C.). The reaction mixture was stirred at room temperature for 16 h, before being cooled to 0° C. and another 8.0 mL (76.1 mmol) of tert-butylamine and 8.26 g (25.3 mmol) of p-toluenesulfonic anhydride were added. The reaction mixture was stirred for 24 h at room temperature, then concentrated and partitioned between 120 mL of water and 150 mL of dichloromethane. The phases were separated and the organic phase was washed eight times with 3N aqueous sodium hydroxide, dried over magnesium sulphate, filtered and evaporated to dryness. The crude product was purified twice by silica gel chromatography (dichloromethane:methanol) to give 277 mg of pure desired product (61) and 714 mg of the product slightly contaminated with p-toluenesulfonic acid. Rt=2.35 min (Method C). Detected mass: 253.1 (M+H+).

1. temperaturebefore being cooled to 0° C.
2. stirringThe reaction mixture was stirred for 24 h at room temperature
3. concentrationconcentrated
4. custompartitioned between 120 mL of water and 150 mL of dichloromethane
5. customThe phases were separated
6. washthe organic phase was washed eight times with 3N aqueous sodium hydroxide
7. dry with materialdried over magnesium sulphate
8. filtrationfiltered
9. customevaporated to dryness
10. customThe crude product was purified twice by silica gel chromatography (dichloromethane:methanol)