Sodium Carbonate → Methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate

HRID 1012252Notes

Reaction equation

HRID 1012252 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[OH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([O:19][CH3:20])=[O:18])=[CH:7][CH:8]=3)[NH:3][C:2]=2[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[OH:21])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 2773454(2-Hydroxyphenyl)boronic acidHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 11995228Methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylateYield 87.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a suspension of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (2 g, 5.95 mmol) obtained in the same manner as in the method described in WO03/010140 and 2-hydroxyphenylboronic acid (1.23 g, 8.91 mmol) in 1,2-dimethoxyethane (20 ml) and water (10 ml) were added lithium chloride (504 mg, 11.9 mmol), sodium carbonate (1.9 g, 17.9 mmol) and tetrakis(triphenylphosphine)palladium (687 mg, 0.59 mmol), and the mixture was heated under reflux for 10 hr. The mixture was allowed to cool to room temperature, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate=3:1-2:1) to give methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (1.81 g, yield 87.7%).

Workup

  1. customobtained in the same manner as in the method
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 10 hr
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel chromatography (hexane:ethyl acetate=3:1-2:1)

Sources & evidence

ORD record
ord-75fd20afb92a4507a99a589640f96178
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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