Chlorosulfonic acid → 4-(Pyridin-4-yloxy)benzene-1-sulfonyl chloride hydrochloride

HRID 23172Notes

Reaction equation

HRID 23172 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:14][S:15](O)(=[O:17])=[O:16]>ClCCCl>[ClH:14].[N:11]1[CH:12]=[CH:13][C:8]([O:1][C:2]2[CH:3]=[CH:4][C:5]([S:15]([Cl:14])(=[O:17])=[O:16])=[CH:6][CH:7]=2)=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 24638Chlorosulfonic acidHCID 2496514-Phenoxypyridine

Product 1

HCID 27352574-(Pyridin-4-yloxy)benzene-1-sulfonyl chloride hydrochloride

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-c0f7722528314e1aae9574ac99115bfd
Source dataset
uspto-grants-2005_02
Patent number
US06849732B2

Reaction notes

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