Potassium Carbonate → 6-chloro-5-[4-(1-methylpyrrolidin-2-yl)phenyl]-1H-indole-3-carbaldehyde

HRID 1054774Notes

Reaction equation

HRID 1054774 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=[O:22])([O-])[O-].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([CH:32]2[CH2:36][CH2:35][CH2:34][N:33]2[CH3:37])=[CH:28][CH:27]=1>O1CCOCC1.CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:22])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:27]=[CH:28][C:29]([CH:32]2[CH2:36][CH2:35][CH2:34][N:33]2[CH3:37])=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2848972-(4-Bromophenyl)-1-methylpyrrolidineHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Product 1

HCID 866987636-chloro-5-[4-(1-methylpyrrolidin-2-yl)phenyl]-1H-indole-3-carbaldehydeYield 53.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 217120691,4-dioxane N,N-dimethylformamideSolvent2×

Procedure

To a suspension of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (290 mg, 1.10 mmol) in mixture of 1,4-dioxane/N,N-dimethylformamide=5:1 (3 mL) was added Vilsmer-salt (330 mg, 3.30 mmol) under nitrogen and stirred at room temperature for 30 minutes. Potassium carbonate (2.0 M in water, 2.9 mL) was added to the above suspension followed by the addition of 2-(4-bromophenyl)-1-methylpyrrolidine (200 mg, 0.84 mmol) in a mixture of 1,4-dioxane/N,N-dimethylformamide=5:1 (3 mL). The mixture was degassed with nitrogen for 10 minutes. The mixture was then treated with Pd(dppf)Cl2 (125 mg, 0.165 mmol). The mixture was stirred at 90° C. under nitrogen for 30 minutes. The mixture was filtered through a celite pad and the filtrate was partitioned between ethyl acetate (10 mL) and water (20 mL), the aqueous phase was extracted three additional times with ethyl acetate (10 mL) and the combined organic phases were washed with brine (15 mL), dried over sodium sulfate, filtered and concentrated to afford crude product which was purified by silica-gel chromatography to afford the title compound (150 mg, 53.2% yield).

Workup

  1. customThe mixture was degassed with nitrogen for 10 minutes
  2. stirringThe mixture was stirred at 90° C. under nitrogen for 30 minutes
  3. filtrationThe mixture was filtered through a celite pad
  4. customthe filtrate was partitioned between ethyl acetate (10 mL) and water (20 mL)
  5. extractionthe aqueous phase was extracted three additional times with ethyl acetate (10 mL)
  6. washthe combined organic phases were washed with brine (15 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford crude product which
  11. customwas purified by silica-gel chromatography

Sources & evidence

ORD record
ord-d024228f3edc44c0b781aa7d6d452b9f
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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