Potassium Carbonate → 1-(propan-2-yl)-4-(2,3,4-trifluorophenyl)-1H-indole-3-carboxaldehyde

HRID 402844Notes

Reaction equation

HRID 402844 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH:14]=[O:15])=[CH:5][N:6]2[CH:11]([CH3:13])[CH3:12].[F:16][C:17]1[C:22]([F:23])=[C:21]([F:24])[CH:20]=[CH:19][C:18]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.Cl[Pd]Cl.[Fe]>[CH3:12][CH:11]([N:6]1[C:7]2[C:3](=[C:2]([C:20]3[CH:19]=[CH:18][C:17]([F:16])=[C:22]([F:23])[C:21]=3[F:24])[CH:10]=[CH:9][CH:8]=2)[C:4]([CH:14]=[O:15])=[CH:5]1)[CH3:13]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27832802,3,4-Trifluorobenzeneboronic acidHCID 772308814-bromo-1-isopropyl-1H-indole-3-carbaldehyde

Product 1

HCID 866852811-(propan-2-yl)-4-(2,3,4-trifluorophenyl)-1H-indole-3-carboxaldehydeYield 68.7%

Reagents, catalysts & solvents 3

HCID 178454869HCID 178454869, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 4-bromo-1-(propan-2-yl)-1H-indole-3-carboxaldehyde (100 mg, 0.376 mmol) and 2,3,4-trifluorophenylboronic acid (79 mg, 0.451 mmol) in dioxane (2 mL) and water (0.5 mL) in a 5 mL microwave reaction vial was added potassium carbonate (156 mg, 1.13 mmol) and dichloro[1,1′-bis(di-t-butylphosphino)ferrocene]palladium (II) (25 mg, 0.038 mmol). The reaction was placed under nitrogen, sealed and heated in a microwave reactor at 140° C. for 15 minutes. The solvent was removed in vacuo and the residue was partitioned with ethyl acetate and aqueous sodium bicarbonate and extracted twice with ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel (COMBI FLASH 24 gm column, gradient of 0-100% ethyl acetate/hexanes) to give the title intermediate (82 mg).

Workup

  1. customsealed
  2. customThe solvent was removed in vacuo
  3. customthe residue was partitioned with ethyl acetate and aqueous sodium bicarbonate
  4. extractionextracted twice with ethyl acetate
  5. washThe organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified on silica gel (COMBI FLASH 24 gm column, gradient of 0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-32e07e7475ba49d9b3530fab92a58071
Source dataset
uspto-grants-2014_06
Patent number
US08742110B2

Reaction notes

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