Cesium fluoride → ethyl 4-chloro-7-o-tolyl-1H-indole-2-carboxylate

HRID 576266Notes

Reaction equation

HRID 576266 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2.[C:17]1([CH3:26])[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.[F-].[Cs+]>O1CCOCC1.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>[Cl:16][C:5]1[CH:4]=[CH:3][C:2]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH3:26])=[C:10]2[C:6]=1[CH:7]=[C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:9]2

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 27332672-Methylphenyl boronic acidHCID 68942988ethyl 7-bromo-4-chloro-1H-indole-2-carboxylate

Product 1

HCID 68936971ethyl 4-chloro-7-o-tolyl-1H-indole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of EXAMPLE 166B (610 mg), o-tolylboronic acid (330 mg), cesium fluoride (930 mg) in dioxane (5 mL) was added tetrakis(triphenylphosphine)palladium (240 mg). The resulting mixture was heated under reflux overnight and concentrated. The residue was diluted with ethyl acetate and saturated ammonium acetate, and the layers were separated. The aqueous layer was extracted with ethyl acetate (×2) and the combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (0-20% ethyl acetate in hexanes) to provide the title compound.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux overnight
  3. concentrationconcentrated
  4. additionThe residue was diluted with ethyl acetate and saturated ammonium acetate
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with ethyl acetate (×2)
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography (0-20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9fdf46fc17b04be9b8e0ebb955449643
Source dataset
uspto-grants-2015_05
Patent number
US09035047B2

Reaction notes

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