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

HRID 2199737Notes

Reaction equation

HRID 2199737 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-627e0c193d8d47288fc24e22e111781d
Source dataset
uspto-grants-2016_06
Patent number
US09359296B2

Reaction notes

Loading…