反应详情

A 12-L three-neck flask equipped with a mechanical mixer, a condenser, and thermocouple was charged with Compound 4 (0.94 mole, 269.1 g) in acetonitrile (ACN; about 4 L), after which chlorosulfonyl isocyanate (0.99 mole, 86 mL) was added (dropwise) via the dropping funnel. Upon completion of the addition, the resulting reaction mixture was refluxed for about 28 minutes. The pH of the mixture was about 0 at this point. The mixture then was cooled slightly, while adding saturated HCl in methanol (MeOH; 500 mL). Subsequently, the mixture was refluxed for about 1 hour, and then allowed to cool to room temperature overnight, during which time crystals formed. The crystals were collected on a sintered glass frit and rinsed with acetonitrile (400 mL and 500 mL). The filter cake was then transferred to a 12 L reactor with a mechanical stirrer. Deionized (DI) water (900 mL) and saturated Na2CO3 (500 mL) were added to afford mixture having a pH of about 10. Next, the solids in the mixture were collected and slurry rinsed with DI water (3×500 mL). The rinsed product was dried via lyophilization to afford about 268.79 g (63.3% yield) of Compound 5.

1. customA 12-L three-neck flask equipped with a mechanical mixer, a condenser
2. additionUpon completion of the addition
3. customthe resulting reaction mixture
4. temperaturewas refluxed for about 28 minutes
5. temperatureThe mixture then was cooled slightly
6. temperatureSubsequently, the mixture was refluxed for about 1 hour
7. customformed
8. customThe crystals were collected on a sintered glass frit
9. washrinsed with acetonitrile (400 mL and 500 mL)
10. customThe filter cake was then transferred to a 12 L reactor with a mechanical stirrer
11. additionDeionized (DI) water (900 mL) and saturated Na2CO3 (500 mL) were added
12. customto afford mixture
13. customNext, the solids in the mixture were collected
14. washslurry rinsed with DI water (3×500 mL)
15. customThe rinsed product was dried via lyophilization