Potassium Carbonate → diethyl 1-(2,2-difluoro-3-{[(4-methylphenyl)sulfonyl]oxy}propyl)-1H-indole-2,6-dicarboxylate

HRID 1748291Notes

Reaction equation

HRID 1748291 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:8]=2)[CH:3]=[C:2]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([O:30][CH2:31][C:32]([F:46])([F:45])[CH2:33]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:29])=[O:28])=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:46][C:32]([F:45])([CH2:31][O:30][S:27]([C:24]1[CH:25]=[CH:26][C:21]([CH3:20])=[CH:22][CH:23]=1)(=[O:29])=[O:28])[CH2:33][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:8]=2)[CH:3]=[C:2]1[C:15]([O:17][CH2:18][CH3:19])=[O:16]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 447174502,2-Difluoropropane-1,3-diyl bis(4-methylbenzenesulfonate)HCID 44754779Diethyl 1H-indole-2,6-dicarboxylate2×

Product 1

HCID 86682393diethyl 1-(2,2-difluoro-3-{[(4-methylphenyl)sulfonyl]oxy}propyl)-1H-indole-2,6-dicarboxylateYield 67.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
135 °C

Procedure

Diethyl 1H-indole-2,6-dicarboxylate (Intermediate A, 3.5 g, 13.6 mmol), 2,2-difluoropropane-1,3-diyl bis(4-methylbenzenesulfonate) (6.0 g, 14.3 mmol) and K2CO3 (3.9 g, 28.5 mmol) are mixed in DMF (36 mL) and the reaction mixture is separated into 3 fractions. Each fraction is heated in a microwave reactor at 135° C. for 1 h. The 3 fractions are combined, and water (300 mL) and EtOAc (300 mL) are added. The aqueous layer is separated and extracted with EtOAc (3×100 mL). The organic layers are combined, washed with water (3×200 mL), dried (Na2SO4) and concentrated. The crude compound is purified by flash column chromatography using EtOAc in heptane to afford the title compound (4.7 g, 59% pure, 38% yield).

Workup

  1. customthe reaction mixture is separated into 3 fractions
  2. additionwater (300 mL) and EtOAc (300 mL) are added
  3. customThe aqueous layer is separated
  4. extractionextracted with EtOAc (3×100 mL)
  5. washwashed with water (3×200 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude compound is purified by flash column chromatography

Sources & evidence

ORD record
ord-4e883693580c4a3ab01b6d54230cdcca
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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