Dichloromethane → 5,7-Difluoro-3-iodo-1-(phenylsulfonyl)-1H-indole

HRID 8114

Reaction equation

HRID 8114 reaction equation
[I:1]Cl.C(Cl)Cl.[F:6][C:7]1[CH:8]=[C:9]2[C:13](=[C:14]([F:16])[CH:15]=1)[NH:12][CH:11]=[CH:10]2.[C:17]1([S:23](Cl)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>N1C=CC=CC=1.C1(C)C=CC=CC=1.[OH-].[Na+].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:17]1([S:23]([N:12]2[C:13]3[C:9](=[CH:8][C:7]([F:6])=[CH:15][C:14]=3[F:16])[C:10]([I:1])=[CH:11]2)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 7369Benzenesulfonyl chlorideHCID 24640Iodine chlorideHCID 27787305,7-difluoro-1H-indole

Product 1

HCID 220147845,7-Difluoro-3-iodo-1-(phenylsulfonyl)-1H-indoleYield 87%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 1049PyridineSolventHCID 1140TolueneSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

The 1.0 M ICl in CH2Cl2 (43 ml, 43 mmol) is added to a solution of 5,7-difluoroindole (6 g, 39 mmol) in 35 ml pyridine under N2 at 0° C. and the resulting mixture is stirred for 30 minutes. The reaction is diluted with toluene and washed with brine, 1N HCl, 1N NaOH, dried (Na2SO4), filtered and concentrated. The crude 3-iodo-5,7-difluoroindole is stirred in toluene (85 ml) and 5 N NaOH (70 ml), tetrabutylammonium bromide (1.25 g, 3.9 mmol), then benzenesulfonyl chloride (6.2 ml, 48 mmol) are added and the resulting mixture is stirred 24 hours. The two phase reaction mixture is diluted with toluene, washed with brine, dried(Na2SO4), filtered, concentrated and the residue is triturated with diethyl ether/petroleum ether. The resulting solid is filtered to give 14.2 g of N-Benzenesulfonyl-3-iodo-5,7-difluoroindole (87%).

Workup

  1. washwashed with brine, 1N HCl, 1N NaOH
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. stirringThe crude 3-iodo-5,7-difluoroindole is stirred in toluene (85 ml)
  6. stirringthe resulting mixture is stirred 24 hours
  7. customThe two phase reaction mixture
  8. washwashed with brine, dried(Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customthe residue is triturated with diethyl ether/petroleum ether
  12. filtrationThe resulting solid is filtered

Sources & evidence

ORD record
ord-563d6e04fa2144da9e95cdda593c8abd
Source dataset
uspto-grants-2006_08
Patent number
US07087635B2

Linked notes

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