反应详情

To a 500 ml 3-necked round bottom flask equipped with reflux condenser, thermometer, magnetic stirrer bar and nitrogen bubbler was charged 2-amino-N-(1-methylethyl)-benzylamine (148.0 g, 0.907 mol), sulfamide (87.9 g, 0.907 mol) and pyridine (975 ml) and the stirred solution heated at reflux for 5 hours under nitrogen (reaction followed by GC and HPLC). The reaction mixture allowed to cool, then pyridine removed under reduced pressure. The residue was dissolved in 5N hydrochloric acid (1000 ml) and ethyl acetate (1000 ml) and the acidic layer was extracted with further ethyl acetate (5×1000 ml). The combined organic layer was washed with 5N hydrochloric acid (250 ml), then extracted with 2N sodium hydroxide (3×1000 ml), the combined aqueous layer washed with diethyl ether (2×500 ml). Ice was then added to the aqueous layer, followed by addition of 5N hydrochloric acid with cooling and stirring of the suspension to pH 1. The oily suspension was stirred at room temperature overnight, the solid filtered and dried at room temperature under vacuum to leave an off-white solid, 3,4-dihydro-3-(1-methylethyl)-1H-2,1,3-benzothiadiazine-2,2-dioxide.

1. customTo a 500 ml 3-necked round bottom flask equipped
2. temperaturewith reflux condenser
3. temperaturethe stirred solution heated
4. temperatureat reflux for 5 hours under nitrogen (reaction followed by GC and HPLC)
5. temperatureto cool
6. custompyridine removed under reduced pressure
7. dissolutionThe residue was dissolved in 5N hydrochloric acid (1000 ml)
8. extractionethyl acetate (1000 ml) and the acidic layer was extracted with further ethyl acetate (5×1000 ml)
9. washThe combined organic layer was washed with 5N hydrochloric acid (250 ml)
10. extractionextracted with 2N sodium hydroxide (3×1000 ml)
11. washthe combined aqueous layer washed with diethyl ether (2×500 ml)
12. additionIce was then added to the aqueous layer
13. additionfollowed by addition of 5N hydrochloric acid
14. temperaturewith cooling
15. stirringThe oily suspension was stirred at room temperature overnight
16. filtrationthe solid filtered
17. customdried at room temperature under vacuum