Carbon Dioxide → 4-Chloro-2-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-N-methoxy-N-methyl-benzamide

HRID 1054493Notes

Reaction equation

HRID 1054493 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([NH:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([C:22]([F:25])([F:24])[F:23])[CH:16]=2)(=[O:14])=[O:13])[CH:3]=1.C(=O)=O.Cl.[CH3:30][NH:31][O:32][CH3:33].O>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:31]([O:32][CH3:33])[CH3:30])=[O:7])=[C:4]([NH:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([C:22]([F:24])([F:25])[F:23])[CH:16]=2)(=[O:14])=[O:13])[CH:3]=1

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 962WaterHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 21286784-Chloro-2-[4-chloro-3-(trifluoromethyl)benzenesulfonamido]benzoic acid

Product 1

HCID 578708014-Chloro-2-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-N-methoxy-N-methyl-benzamideYield 73%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-chloro-2-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-benzoic acid (5.0 g, 12.1 mmol) in THF (20 mL) was added N,N′-carbonyldiimidazole (CDI, 2.45 g, 15.13 mmol) in portions (Caution!: CO2↑). The resulting reaction mixture was then heated at reflux. After 4 hours, reaction mixture was cooled to room temperature and charged with N,O-dimethylhydroxylamine hydrochloride (1.3 g, 13.31 mmol) and heated at reflux for 1 hour. Water (100 mL) was added followed by EtOAc (100 mL) with stirring. EtOAc layer was separated and aqueous layer was further extracted with EtOAc (2×50 mL). Combined EtOAc layers were washed with aq. 2N HCl (50 mL), saturated NaHCO3 solution (50 mL), brine (50 mL), dried (Na2SO4) and evaporated. Obtained crude product was purified by automated normal-phase chromatography (50% EtOAc in hexanes) to afford title compound (4.0 g) in 73% yield. MS (ES) M+H expected 457.0. found 456.9.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas then heated
  3. temperatureat reflux
  4. customreaction mixture
  5. temperatureheated
  6. temperatureat reflux for 1 hour
  7. customEtOAc layer was separated
  8. extractionaqueous layer was further extracted with EtOAc (2×50 mL)
  9. washCombined EtOAc layers were washed with aq. 2N HCl (50 mL), saturated NaHCO3 solution (50 mL), brine (50 mL)
  10. dry with materialdried (Na2SO4)
  11. customevaporated
  12. customObtained crude product
  13. customwas purified by automated normal-phase chromatography (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-279800645296494487636b4719e2ed7a
Source dataset
uspto-grants-2016_07
Patent number
US09394307B2

Reaction notes

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