反应详情

温度

10 °C

A 250 ml three necked flask, equipped with mechanical stirrer, Dean-Stark trap and condenser, was charged with 1,2-benzisoxazole-3-methanesulfonic acid methyl ester (10 grams, 0.044 mole, obtained from a commercial vendor) and toluene (100 ml). The suspension was heated to reflux while azeotropic distillation of water was performed, during 2 hours. The mixture was thereafter cooled under nitrogen atmosphere to 10° C. and DMF (0.36 ml, 0.0044 mole, 0.1 molar equivalent) was added to the mixture. Oxalyl chloride (4.1 ml, 0.047 mole, 1.07 molar equivalent) was then added drop-wise at 10-15° C. during 30 minutes and the reaction mixture was heated to 40° C. and was kept at this temperature for 4 hours. Ammonia (gas) (3.0 grams, 4 molar equivalents) was then bubbled into the reaction mixture at 10-18° C. during 2 hours and the reaction mixture was kept at ambient temperature overnight. The obtained precipitate was collected by filtration and slurried in 25% ammonium hydroxide (40 ml) at ambient temperature for 2 hours. The obtained solid was collected by filtration, washed with water and dried under reduced pressure at 50° C., overnight to obtain crude zonisamide (7.4 grams, 80.4% yield) having a purity of 98.7%, as determined by HPLC.

1. temperatureThe suspension was heated
2. temperaturethe reaction mixture was heated to 40° C.
3. waitwas kept at this temperature for 4 hours
4. customAmmonia (gas) (3.0 grams, 4 molar equivalents) was then bubbled into the reaction mixture at 10-18° C. during 2 hours
5. waitthe reaction mixture was kept at ambient temperature overnight
6. filtrationThe obtained precipitate was collected by filtration
7. waitslurried in 25% ammonium hydroxide (40 ml) at ambient temperature for 2 hours
8. filtrationThe obtained solid was collected by filtration
9. washwashed with water
10. customdried under reduced pressure at 50° C., overnight