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

HRID 338295Notes

Reaction equation

HRID 338295 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].CC1(C)COB([C:21]2[CH:26]=[CH:25][C:24]([C:27]3([CH2:30][OH:31])[CH2:29][CH2:28]3)=[CH:23][CH:22]=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]>[OH:31][CH2:30][C:27]1([C:24]2[CH:25]=[CH:26][C:21]([C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][C:10]=3[CH3:11])[NH:7][CH:6]=[C:5]4[CH:12]=[O:13])=[CH:22][CH:23]=2)[CH2:29][CH2:28]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 823888555-bromo-6-methyl-1H-indole-3-carbaldehydeHCID 86698629(1-(4-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)cyclopropyl)methanol

Product 1

HCID 866986415-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-6-methyl-1H-indole-3-carbaldehydeYield 74.1%

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-6-methyl-1H-indole-3-carbaldehyde (200 mg, 0.84 mmol) and {1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]cyclopropyl}methanol (242 mg, 0.93 mmol) in toluene (6 mL) and EtOH (2.0 mL) was added to a solution of potassium carbonate (350 mg, 2.52 mmol) in water (1.0 mL) and Pd(dppf)Cl2 (34 mg, 0.042 mmol) at room temperature under N2. TLC (petroleum ether/EtOAc=1:1) showed the reaction was complete. 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 and concentrated to give a crude ARRR!!!!, which was purified by column chromatography to give the title compound (190 mg, 74%) as a yellow solid.

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. customto give a crude ARRR
  6. custom, which was purified by column chromatography

Sources & evidence

ORD record
ord-cb486269a8bd433aae74396d887f39ce
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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