Hydrochloric Acid → 1-chloro-N-(2-chloro-4-fluorophenyl)methanesulfonamide

HRID 432960Notes

Reaction equation

HRID 432960 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[Cl:10][CH2:11][S:12](Cl)(=[O:14])=[O:13].C(N(CC)CC)C.Cl>C1(C)C=CC=CC=1>[Cl:10][CH2:11][S:12]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([F:9])=[CH:8][C:2]=1[Cl:1])(=[O:14])=[O:13]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 75013Benzenamine, 2-chloro-4-fluoro-HCID 77054(Chloromethyl)sulfonyl chloride

Product 1

HCID 187608471-chloro-N-(2-chloro-4-fluorophenyl)methanesulfonamideYield 75%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
7.5 °C

Procedure

72.8 g (0.5 mol) of 2-chloro-4-fluoroaniline were dissolved in 400 mL of toluene and cooled to 5-10° C., and then 79 g (0.53 mol) of chloromethylsulfonyl chloride were added slowly with stirring. The temperature was kept below 10-15° C. The mixture was then heated to 40° C. for 30 minutes and cooled again to 5-10° C. At this temperature, 101 g (1 mol) of triethylamine was added with stirring and cooling. After the addition was complete, the mixture was stirred at 40° C. for an additional 8 hours and then poured into 1050 mL of 6 N hydrochloric acid. The organic phase was separated and the aqueous phase was washed with toluene. The combined organic phases were poured with vigorous stirring into 12.5% sodium hydroxide solution. The basic aqueous phase was separated and the organic phase was washed with aqueous sodium hydroxide solution. The combined aqueous phases were treated with active carbon and filtered. 6 N hydrochloric acid was added with cooling until the pH was below 7. The precipitated product was filtered off, washed with water and dried to yield 96.8 g (75%) of the title compound as a solid melting at 83-85° C.

Workup

  1. customwas kept below 10-15° C
  2. temperatureThe mixture was then heated to 40° C. for 30 minutes
  3. temperaturecooled again to 5-10° C
  4. stirringwith stirring
  5. temperaturecooling
  6. additionAfter the addition
  7. stirringthe mixture was stirred at 40° C. for an additional 8 hours
  8. customThe organic phase was separated
  9. washthe aqueous phase was washed with toluene
  10. additionThe combined organic phases were poured
  11. stirringwith vigorous stirring into 12.5% sodium hydroxide solution
  12. customThe basic aqueous phase was separated
  13. washthe organic phase was washed with aqueous sodium hydroxide solution
  14. additionThe combined aqueous phases were treated with active carbon
  15. filtrationfiltered
  16. addition6 N hydrochloric acid was added
  17. temperaturewith cooling until the pH was below 7
  18. filtrationThe precipitated product was filtered off
  19. washwashed with water
  20. customdried

Sources & evidence

ORD record
ord-25f791a2f634411c9ee8d8fb7f784347
Source dataset
uspto-grants-2003_12
Patent number
US06664400B2

Reaction notes

Loading…