Potassium Carbonate → 4,6-difluoro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde

HRID 1054627Notes

Reaction equation

HRID 1054627 reaction equation
Br[C:2]1[C:3]([F:14])=[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)COB([C:22]2[CH:27]=[CH:26][C:25]([C:28]3([CH2:31][OH:32])[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)OC1.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:14][C:3]1[C:2]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3([CH2:31][OH:32])[CH2:29][CH2:30]3)=[CH:24][CH:23]=2)=[C:10]([F:11])[CH:9]=[C:8]2[C:4]=1[C:5]([CH:12]=[O:13])=[CH:6][NH:7]2

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 866985785-Bromo-4,6-difluoro-1H-indole-3-carbaldehydeHCID 86698629(1-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)cyclopropyl)methanol

Product 1

HCID 866986304,6-difluoro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehydeYield 28%

Reagents, catalysts & solvents 4

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

Procedure

A solution of 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde (200 mg, 0.77 mmol) and {1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]cyclopropyl}methanol (200 mg, 0.77 mmol) in toluene (6 mL) and EtOH (2 mL) was added a solution of potassium carbonate (318 mg, 2.31 mmol) in water (1.0 mL) and Pd(dppf)Cl2 (31 mg, 0.04 mmol) at room temperature under N2. The reaction was cooled to room temperature, and extracted with ethyl acetate (20 mL×3). The organic layers were washed with brine (20 mL), dried over sodium sulfate, concentrated, and purified by column chromatography to give the title compound (70 mg, 28%) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 10.00 (s, 1 H), 8.12 (s, 1 H), 7.49 (d, 2 H), 7.40 (d, 2 H), 7.19 (d, 1 H), 3.69 (s, 2 H), 0.89 (s, 4 H).

Workup

  1. extractionextracted with ethyl acetate (20 mL×3)
  2. washThe organic layers were washed with brine (20 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-4e9eaac2dec14627ad99f5ab60156e48
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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