反应详情

温度

140 °C

To a five liter flask equipped with thermometer, packed distillation column, condenser, and stirrer, under a nitrogen atmosphere is added 3300 ml mixed xylenes, 80 g (0.297 mole) methyl 3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide, 32 g (0.340 mole) 2-aminopyridine and 8 g of activated carbon (Darco G-60* or Darco KBB*). The mixture is heated at reflux (ca. 140° C.) for 28 hours while slowly distilling off methanol and xylene at a rate of about 25 ml per hour for the first 8 hours, then at a rate of 5-10 ml per hour for the remaining reflux period, while adding fresh xylene to maintain a reaction volume of about 3500 ml. After 28 hours, the reaction mixture is cooled slightly (~100° C.) and filtered to remove carbon. The carbon cake was washed with warm xylene (100 ml), the filtrate and washings cooled slowly under a nitrogen atmosphere with rapid stirring to 25°-50° C. Stirring was continued for one hour to allow for complete crystallization. The crystals were collected by filtration, the mother liquor concentrated to about 1500 ml, cooled under nitrogen to 0°-5° C., filtered, the cake washed with 100 ml cold xylene and the crystals dried under vacuum below 60° C. for several hours. The yield is 76.7-84.6 g (78-86% of theory). Average throughput 24.4 g/liter of solvent.

1. customTo a five liter flask equipped with thermometer,
2. distillationdistillation column, condenser, and stirrer
3. additionunder a nitrogen atmosphere is added 3300 ml
4. temperatureThe mixture is heated
5. distillationwhile slowly distilling off methanol and xylene at a rate of about 25 ml per hour for the first 8 hours
6. temperatureat a rate of 5-10 ml per hour for the remaining reflux period
7. additionwhile adding fresh xylene
8. temperatureto maintain a reaction volume of about 3500 ml
9. temperaturethe reaction mixture is cooled slightly (~100° C.)
10. filtrationfiltered
11. customto remove carbon
12. washThe carbon cake was washed with warm xylene (100 ml)
13. temperaturethe filtrate and washings cooled slowly under a nitrogen atmosphere
14. stirringStirring
15. waitwas continued for one hour
16. customto allow for complete crystallization
17. filtrationThe crystals were collected by filtration
18. concentrationthe mother liquor concentrated to about 1500 ml
19. temperaturecooled under nitrogen to 0°-5° C.
20. filtrationfiltered
21. washthe cake washed with 100 ml cold xylene
22. customthe crystals dried under vacuum below 60° C. for several hours