Potassium Carbonate → 1-Boc-2-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]-6-methoxyindole

HRID 1009639Notes

Reaction equation

HRID 1009639 reaction equation
[C:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][C:18](F)(F)F)[CH:15]=2)[CH:10]=[C:9]1B(O)O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].I[C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH2:36][CH2:35][CH2:34][S:33]2(=[O:38])=[O:37])=[CH:28][CH:27]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[CH:10]=[C:9]1[C:26]1[CH:27]=[CH:28][C:29]([N:32]2[CH2:36][CH2:35][CH2:34][S:33]2(=[O:38])=[O:37])=[CH:30][CH:31]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 147632212-(4-Iodophenyl)isothiazolidine-1,1-dioxideHCID 57355675(1-(tert-Butoxycarbonyl)-6-(trifluoromethoxy)-1H-indol-2-yl)boronic acid

Product 1

HCID 594306781-Boc-2-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]-6-methoxyindole

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-Boc-6-trifluoromethoxyindole-2-boronic acid prepared above (0.74 g, 2.1 mmol), 2-(4-iodophenyl)isothiazolidine-1,1-dioxide (0.76 g, 2.4 mmol), and PdCl2(dppf) (0.08 g, 0.1 mmol) in DMF (6.0 mL), is added K2CO3 solution (3.2 mL, 2.0 M, 6.4 mmol). The mixture is stirred at room temperature overnight and then poured into ice-water (100 mL). The precipitate is collected and washed with water and purified by flash column chromatography (silica gel, DCM/EtOAc, 9/1) to furnish 1-Boc-2-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]-6-methoxyindole, which is treated with 50% TFA in DCM (15 mL) at room temperature for 1 h. After the removal of the volatiles, the residue is carefully stirred with saturated NaHCO3 for 0.5 h. The precipitate is collected via filtration and washed thoroughly with water and dried to provide essentially pure 1-H-2-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]-6-trifluoromethoxyindole.

Workup

  1. customThe precipitate is collected
  2. washwashed with water
  3. custompurified by flash column chromatography (silica gel, DCM/EtOAc, 9/1)

Sources & evidence

ORD record
ord-ff608a1714c94bbf8c58b63c2f708fe2
Source dataset
uspto-grants-2011_07
Patent number
US07973069B2

Reaction notes

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