Potassium Carbonate → 1-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]cyclobutanecarboxylic acid

HRID 338410Notes

Reaction equation

HRID 338410 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)([O-])[O-:20].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([C:36]([OH:38])=[O:37])[CH2:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1>O1CCOCC1.CN(C=O)C.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:20])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:31]=[CH:30][C:29]([C:32]2([C:36]([OH:38])=[O:37])[CH2:35][CH2:34][CH2:33]2)=[CH:28][CH:27]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 167699191-(4-Bromophenyl)cyclobutane-1-carboxylic acidHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Product 1

HCID 866987471-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]cyclobutanecarboxylic acidYield 63.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (200 mg, 0.80 mmol) in 1,4-dioxane (5 mL) and DMF (1 mL) was added N,N-dimethylformiminium chloride (250 mg, 2.00 mmol). The reaction mixture was sealed and stirred at room temperature for 10 minutes. To the resulting slurry was added 2M aqueous potassium carbonate (2 mL, 4 mmol), 1-(4-bromophenyl)cyclobutanecarboxylic acid (255 mg, 1.00 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (50 mg). The reaction mixture was degassed with nitrogen, sealed, and heated to 90° C. for 30 minutes. The reaction was quenched with H2O (20 mL), then washed with ethyl acetate (3×20 mL). The combined organic phases were dried and concentrated in vacuo to give the title compound (180 mg, 63% yield) in crude form, which was used in the next step without further purification. 1H NMR (400 MHz, CD3OD) δ 9.90 (s, 1H), 8.17 (s, 1H), 8.13 (s, 1H), 7.62-7.61 (m, 1H), 7.48-7.45 (m, 2H), 7.41-7.37 (m, 2H), 2.86-2.79 (m, 2H), 2.62-2.45 (m, 2H), 2.05-2.01 (m, 2H).

Workup

  1. customThe reaction mixture was sealed
  2. customThe reaction mixture was degassed with nitrogen
  3. customsealed
  4. temperatureheated to 90° C. for 30 minutes
  5. customThe reaction was quenched with H2O (20 mL)
  6. washwashed with ethyl acetate (3×20 mL)
  7. customThe combined organic phases were dried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a45c8c05e1d24f02a908d958239814a8
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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