反应详情

温度

25 °C

To a solution of 4-phenoxypyridine (6.84 g) in 20 mL of 1,2-dichloroethane at 0° C. was added 8.0 mL of chlorosulfonic acid in a dropwise manner. After 10 minutes, the ice bath was removed and the solution was allowed to warm to 25° C. After an additional 1 hour, the solution was heated to 40° C. for 3 hours, and then cooled to 25° C., and oxalyl chloride (4.4 mL) was added. The solution was heated to 50° C. for 16 hours, and then an additional 2.2 mL of oxalyl chloride was added. After 5 hours more at 5° C., the solution was cooled to 25° C., and poured with rapid stirring into 250 mL of diethyl ether. After 1 minute, the solids were allowed to settle and the supernatant was decanted. The residue was suspended in 3:1 toluene:dichloromethane (250 mL) at about 5° C. and 50 mL of 1.6 M aqueous K3PO4 was added with stirring. After about 30 seconds, the mixture was transferred to a separatory funnel and the layers were separated. The organic layer was washed with 25 mL of 1 N pH 7 phosphate buffer and with 10 mL of brine, and the combined aqueous layers were extracted with 50 mL of toluene. The combined organic layers were dried over sodium sulfate then filtered through a glass-fiber filter. To the filtrate was immediately added 11 mL of 4 M HCl in dioxane and the solution was then concentrated. Partial concentration from dichloromethane:t-butyl methyl ether and filtration gave 2.11 g of 4-((pyrid-4-yl)oxy)benzenesulfonyl chloride hydrochloride.

1. customthe ice bath was removed
2. waitAfter an additional 1 hour
3. temperaturethe solution was heated to 40° C. for 3 hours
4. temperaturecooled to 25° C.
5. additionoxalyl chloride (4.4 mL) was added
6. temperatureThe solution was heated to 50° C. for 16 hours
7. additionan additional 2.2 mL of oxalyl chloride was added
8. waitAfter 5 hours more at 5° C.
9. temperaturethe solution was cooled to 25° C.
10. additionpoured
11. waitAfter 1 minute
12. customthe supernatant was decanted
13. additiondichloromethane (250 mL) at about 5° C. and 50 mL of 1.6 M aqueous K3PO4 was added
14. stirringwith stirring
15. waitAfter about 30 seconds
16. customthe mixture was transferred to a separatory funnel
17. customthe layers were separated
18. washThe organic layer was washed with 25 mL of 1 N pH 7 phosphate buffer and with 10 mL of brine
19. extractionthe combined aqueous layers were extracted with 50 mL of toluene
20. dry with materialThe combined organic layers were dried over sodium sulfate
21. filtrationthen filtered through a glass-fiber
22. filtrationfilter
23. concentrationthe solution was then concentrated
24. concentrationPartial concentration from dichloromethane
25. filtrationt-butyl methyl ether and filtration