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

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.

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)

ORD-Eintrag

ord-a4b2bf56f2264c9798972d897845bdc3

Quelldatensatz

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08546408B2