Potassium Carbonate → 5-chloro-3-hydroxy-3-(2-methoxyphenyl)-1-{[4-methoxy-2-(trifluoromethoxy)phenyl]sulfonyl}-1,3-dihydro-2H-indol-2-one

HRID 1662597Notes

Reaction equation

HRID 1662597 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([OH:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19].[H-].[Na+].[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[C:27]([O:35][C:36]([F:39])([F:38])[F:37])[CH:26]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:31]([C:28]1[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][C:27]=1[O:35][C:36]([F:37])([F:38])[F:39])(=[O:33])=[O:32])[C:6](=[O:11])[C:5]2([OH:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[O:18][CH3:19]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 219059555-Chloro-3-hydroxy-3-(2-methoxyphenyl)indolin-2-oneHCID 866256844-Methoxy-2-(trifluoromethoxy)benzene sulfonyl chloride

Product 1

HCID 674298505-chloro-3-hydroxy-3-(2-methoxyphenyl)-1-{[4-methoxy-2-(trifluoromethoxy)phenyl]sulfonyl}-1,3-dihydro-2H-indol-2-oneYield 48.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent2×

Procedure

Under nitrogen atmosphere, to a solution of 5.00 g of 5-chloro-3-hydroxy-3-(2-methoxyphenyl)-1,3-dihydro-2H-indol-2-one, which is the compound described in Preparation 1.1A of brochure Publication No. WO01/5513,0 in DMF (50 ml) was added 760 mg of NaH under ice cooling, then, the reaction mixture was warmed to room temperature and stirred for 30 minutes. To the stirred solution, under cooling at −20° C., was added dropwise a solution of 5.52 g of 4-methoxy-2-(trifluoromethoxy)benzene sulfonyl chloride in DMF (10 ml) over 3 minutes, then, the solution was stirred at the same temperature for 5 hours. After warming to 0° C., to the reaction solution was added CHCl3 and an aqueous solution of 5% K2CO3, and the solution was stirred at room temperature for 30 minutes. The liquid separation of the stirred solution was performed, then the aqueous layer was extracted with CHCl3, the combined organic layer was washed with saturated brine, dried over MgSO4, then, the drying agent was separated by filtration, and was solvent under reduced pressure. The obtained residue was purified by column chromatography (silicagel 60; mobile phase: EtOAc/n-hexane=1/1; v/v) to obtain 4.55 g of the title compound (orange color solid).

Workup

  1. temperatureTo the stirred solution, under cooling at −20° C.
  2. stirringthe solution was stirred at the same temperature for 5 hours
  3. temperatureAfter warming to 0° C., to the reaction solution
  4. customThe liquid separation of the stirred solution
  5. extractionthe aqueous layer was extracted with CHCl3
  6. washthe combined organic layer was washed with saturated brine
  7. dry with materialdried over MgSO4
  8. customthe drying agent was separated by filtration
  9. customThe obtained residue was purified by column chromatography (silicagel 60; mobile phase: EtOAc/n-hexane=1/1; v/v)

Sources & evidence

ORD record
ord-ab113497c83740e4be7c73a4770d67c7
Source dataset
uspto-grants-2011_10
Patent number
US08030499B2

Reaction notes

Loading…