Hydrochloric Acid → Methyl 4-(chlorosulfonyl)-2-fluorobenzoate

HRID 401760Notes

Reaction equation

HRID 401760 reaction equation
[ClH:1].N[C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:13])[CH:4]=1.Cl.N([O-])=O.[Na+].[S:19](=[O:21])=[O:20]>O.CC(O)=O.[Cu]Cl.CCCCCC>[Cl:1][S:19]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:13])[CH:4]=1)(=[O:21])=[O:20]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 1119Sulfur DioxideHCID 23668193Sodium NitriteHCID 68517562Methyl 4-amino-2-fluorobenzoate hydrochloride

Product 1

HCID 57732146Methyl 4-(chlorosulfonyl)-2-fluorobenzoateYield 50,649.398%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 8058HexaneSolvent

Procedure

To a suspension of methyl 4-amino-2-fluorobenzoate hydrochloride (Preparation 12, 33.2 g, 0.154 mmol, 1 eq) in a 1:1 mixture of concentrated HCl and water (70 ml:70 ml) cooling in an ice bath was added a solution of sodium nitrite (11.71 g, 0.169 mol, 1.1 eq) in warm water (20 ml) dropwise maintaining the temperature below 50° C. The reaction mixture was allowed to stir for 10 minutes then filtered through a pad of Celite and the solid washed with water. The filtrate was added portionwise to a solution of sulphur dioxide (49.4 g, 0.771 mmol, 5 eq) and copper (1) chloride (100 mg) in AcOH (120 ml) at 0° C. and the reaction mixture stirred for 30 minutes. The mixture was extracted with DCM (3×150 ml), washed with saturated sodium hydrogen carbonate, water and brine, dried over magnesium sulphate, filtered and evaporated in vacuo. The crude material was purified by column chromatography eluting with 10% ethyl acetate:hexane to yield the title compound as a red oil (19.68 g, 0.078 mol, 50%).

Workup

  1. temperaturecooling in an ice bath
  2. temperaturedropwise maintaining the temperature below 50° C
  3. filtrationthen filtered through a pad of Celite
  4. washthe solid washed with water
  5. stirringthe reaction mixture stirred for 30 minutes
  6. extractionThe mixture was extracted with DCM (3×150 ml)
  7. washwashed with saturated sodium hydrogen carbonate, water and brine
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe crude material was purified by column chromatography
  12. washeluting with 10% ethyl acetate

Sources & evidence

ORD record
ord-161e331dc42b47189ff86387c76b1b62
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Reaction notes

Loading…