反应详情

Methyl 3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide (50 g.) is added to a solution of sodium hydroxide (160 g.) in water (500 ml.) at 70° C. The resulting lemon-yellow slurry is then heated at 90°-95° C. for 45 minutes and then cooled to room temperature is an ice-water bath. The pH of the reaction mixture is adjusted to 1-1.5 by gradual addition of concentrated hydrochloric acid (350 ml.). Ice chips are added as necessary to keep the temperature below 35° C. The acid product precipitates and is granulated by stirring at 10°-15° C. for 15 minutes. It is recovered by suction filtration, washed with water (100 ml.) and reslurried in water (250 ml.) for a half hour to remove excess hydrochloric acid. It is again filtered with suction and washed with water (100 ml.). Twenty-five grams of the wet filter cake (total wet filter cake is 25.5 g.) is dissolved in warm methanol (150 ml.), the solution filtered and water (50 ml.) added to the filtrate. The addition of seed crystals causes immediate precipitation of product. The slurry is granulated by stirring at about 10° C. for a half hour. The white crystalline product is separated by filtration, washed with water and air-dried. Yield = 13.2 g., M.p. 144°-146° C.

1. temperatureThe resulting lemon-yellow slurry is then heated at 90°-95° C. for 45 minutes
2. additionIce chips are added as necessary
3. customthe temperature below 35° C
4. customThe acid product precipitates
5. filtrationIt is recovered by suction filtration
6. washwashed with water (100 ml.)
7. waitreslurried in water (250 ml.) for a half hour
8. customto remove excess hydrochloric acid
9. filtrationIt is again filtered with suction
10. washwashed with water (100 ml.)
11. dissolutionTwenty-five grams of the wet filter cake (total wet filter cake is 25.5 g.) is dissolved in warm methanol (150 ml.)
12. filtrationthe solution filtered
13. additionwater (50 ml.) added to the filtrate
14. additionThe addition of seed crystals
15. customprecipitation of product
16. stirringby stirring at about 10° C. for a half hour
17. customThe white crystalline product is separated by filtration
18. washwashed with water
19. customair-dried