Toluene → 6-[4-(Trifluoromethoxy)phenyl]-1H-indole

HRID 1791406Notes

Reaction equation

HRID 1791406 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[F:11][C:12]([F:24])([F:23])[O:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:11][C:12]([F:23])([F:24])[O:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[CH:7][NH:8]3)=[CH:4][CH:3]=2)=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 6764936-BromoindoleHCID 27343864-(Trifluoromethoxy)phenylboronic acid

Product 1

HCID 220329516-[4-(Trifluoromethoxy)phenyl]-1H-indole

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

The mixture of 6-bromo-1H-indole (1.22 g, 6.22 mmol), 4-trifluoromethoxyphenyl boronic acid (1.41 g, 6.84 mmol), tetrakis(triphenylphosphine)palladium (0.213 g, 0.184 mmol) and sodium carbonate (2.64 g, 24.9 mmoles) in water (12.5 mL), ethanol (4 mL), and toluene (25 mL) was heated at reflux for 1.5 hours then cooled to room temperature. The mixture was then evaporated to dryness and the residue was partitioned in methylene chloride and water. The organic phase was washed with water, brine, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was purified by flash chromatography using 10-30% chloroform in hexane as an eluant. The title compound was obtained as a white solid (0.874 g, 51%), mp: 165-166° C. 1HNMR (300 MHz, DMSO-d6): δ 11.25 (s, 1H), 7.8 (d, 2H, J=7.0 Hz), 7.65 (d, 2H, J=7.0 Hz), 7.4-7.5 (m, 3H), 7.3 (d, 1H, J=8.8 Hz), and 6.45 ppm (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 hours
  3. customThe mixture was then evaporated to dryness
  4. customthe residue was partitioned in methylene chloride
  5. washThe organic phase was washed with water, brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated to dryness
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-1af1d6e48acc44038280d9abc9a403e4
Source dataset
uspto-grants-2006_07
Patent number
US07074817B2

Reaction notes

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