Potassium Carbonate → 6-Fluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carbaldehyde

HRID 338223Notes

Reaction equation

HRID 338223 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].CC1(C)C(C)(C)OB([C:22]2[CH:27]=[CH:26][C:25]([C:28]3([OH:32])[CH2:31][CH2:30][CH2:29]3)=[CH:24][CH:23]=2)O1.C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-]>C1(C)C=CC=CC=1.CCO.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]>[F:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([CH:12]=[O:13])=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:22]1[CH:27]=[CH:26][C:25]([C:28]2([OH:32])[CH2:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 713020411-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutanolHCID 735543615-Bromo-6-fluoro-1H-indole-3-carbaldehyde

Product 1

HCID 866985746-Fluoro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carbaldehydeYield 51%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A mixture of 5-bromo-6-fluoro-1H-indole-3-carbaldehyde (90 mg, 0.37 mmol), 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutanol (120 mg, 0.44 mmol), 2N aqueous potassium carbonate (0.75 mL, 1.49 mmol) in toluene (3.0 mL) and EtOH (1.0 mL) was degassed with N2 for 3 minutes, and treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (30.0 mg, 0.041 mmol). The mixture was subjected to microwave irradiation conditions at 110° C. for 2 hours. The reaction mixture was cooled to room temperature, poured into half-saturated aqueous NH4Cl solution (15 mL) and extracted with EtOAc (6×15 mL). The combined organic layer were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (9-50% EtOAc/petroleum ether) to afford the title compound (58.0 mg, 51% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.0 (s, 1H), 8.42 (s, 1H), 8.20 (d, J=8.00 Hz, 1H), 7.66 (d, J=8.40 Hz, 2H), 7.59 (d, J=8.40 Hz, 2H), 7.50 (d, J=10.80 Hz, 1H), 2.48 (m, 2H), 2.41 (m, 2H), 2.02 (m, 1H), 1.76 (m, 1H).

Workup

  1. customwas degassed with N2 for 3 minutes
  2. customirradiation conditions at 110° C. for 2 hours
  3. extractionextracted with EtOAc (6×15 mL)
  4. washThe combined organic layer were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (9-50% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-20422a91414947c69ea18a273203f818
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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