Hydrochloric Acid → Methyl 3-chloro-4-(chlorosulfonyl)benzoate

HRID 401755Notes

Reaction equation

HRID 401755 reaction equation
N[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[Cl:12].[ClH:13].N([O-])=O.[Na+].[S:18](=[O:20])=[O:19]>O.CC(O)=O.[Cu]Cl>[Cl:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[S:18]([Cl:13])(=[O:20])=[O:19])[C:6]([O:8][CH3:9])=[O:7]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1119Sulfur DioxideHCID 1515284Methyl 4-Amino-3-chlorobenzoateHCID 23668193Sodium Nitrite

Product 1

HCID 47002988Methyl 3-chloro-4-(chlorosulfonyl)benzoateYield 50%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

To a suspension of methyl 4-amino-3-chlorobenzoate (33 g, 146 mmol, 1 eq) in a 1:1 mixture of concentrated HCl and water (140 ml) cooling in an ice/MeOH bath was added a solution of sodium nitrite (11.1 g, 160 mmol, 1.1 eq) in warm water (20 ml) dropwise, ensuring that the reaction temperature was maintained below 5° C. The mixture was filtered through a pad of Celite and the solids washed with water. The resulting filtrate was added portionwise to a mixture of sulphur dioxide (47 g, 729 mmol, 5 eq) and copper (I) chloride (catalytic) in AcOH, maintaining the reaction temperature below 10° C. The reaction mixture was extracted into DCM (600 ml), washed with water (600 ml), dried over sodium sulphate, filtered and the solvent evaporated in vacuo. The residue was redissolved in DCM, washed with saturated sodium hydrogen carbonate, dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was purified by column chromatography eluting with 0-15% ethyl acetate:hexane then triturated with hexane to yield the title compound (19.6 g, 73.6 mmol, 50%).

Workup

  1. temperaturecooling in an ice/MeOH bath
  2. temperaturewas maintained below 5° C
  3. filtrationThe mixture was filtered through a pad of Celite
  4. washthe solids washed with water
  5. temperaturemaintaining the reaction temperature below 10° C
  6. extractionThe reaction mixture was extracted into DCM (600 ml)
  7. washwashed with water (600 ml)
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. customthe solvent evaporated in vacuo
  11. dissolutionThe residue was redissolved in DCM
  12. washwashed with saturated sodium hydrogen carbonate
  13. dry with materialdried over sodium sulphate
  14. filtrationfiltered
  15. customevaporated in vacuo
  16. customThe crude material was purified by column chromatography
  17. washeluting with 0-15% ethyl acetate
  18. customhexane then triturated with hexane

Sources & evidence

ORD record
ord-a0fae7c029db4f88a99ddee158663abe
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Reaction notes

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