Potassium Carbonate → 4,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carbaldehyde

HRID 1054635Notes

Reaction equation

HRID 1054635 reaction equation
CC1(C)COB([C:8]2[CH:13]=[CH:12][C:11]([C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])=[CH:10][CH:9]=2)OC1.Br[C:21]1[C:22]([F:33])=[C:23]2[C:27](=[CH:28][C:29]=1[F:30])[NH:26][CH:25]=[C:24]2[CH:31]=[O:32].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO.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]>[F:33][C:22]1[C:21]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([CH3:17])([CH3:18])[CH2:15][OH:16])=[CH:12][CH:13]=2)=[C:29]([F:30])[CH:28]=[C:27]2[C:23]=1[C:24]([CH:31]=[O:32])=[CH:25][NH:26]2

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 866985785-Bromo-4,6-difluoro-1H-indole-3-carbaldehydeHCID 866986392-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)-2-methylpropan-1-ol

Product 1

HCID 866986404,6-difluoro-5-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]-1H-indole-3-carbaldehydeYield 32%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 2-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]-2-methylpropan-1-ol (102 mg, 0.386 mmol) and 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde (100 mg, 0.386 mmol) in toluene (6 mL) and EtOH (2 mL) was added a solution of potassium carbonate (160 mg, 1.159 mmol) in water (1.0 mL) and Pd(dppf)Cl2 (15.8 mg, 0.019 mmol) at room temperature under N2. The reaction was cooled to room temperature, and extracted with ethyl acetate (10 mL×2). The organic layers were washed with brine (10 mL), and dried over sodium sulfate and concentrated to give a crude residue, which was purified by column chromatography to give the title compound (40 mg, 32%) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 10.0 (s, 1 H), 8.13 (s, 1 H), 7.51 (d, 2 H), 7.40 (d, 2 H), 7.19 (d, 1 H), 3.63 (s, 2 H), 1.36 (s, 6 H).

Workup

  1. extractionextracted with ethyl acetate (10 mL×2)
  2. washThe organic layers were washed with brine (10 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customto give a crude residue, which
  6. customwas purified by column chromatography

Sources & evidence

ORD record
ord-75cd2b174edc49e4baa40e7cd6f64bef
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

Loading…