Sodium Bicarbonate → methyl 3-cyclohexyl-2-{2-[2-(tetrahydropyran-2-yloxy)ethylsulfanyl]phenyl}-1H-indole-6-carboxylate

HRID 1012350Notes

Reaction equation

HRID 1012350 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8][CH2:9][CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.C(=O)([O-])O.[Na+].[CH:23]1([C:29]2[C:37]3[C:32](=[CH:33][C:34]([C:38]([O:40][CH3:41])=[O:39])=[CH:35][CH:36]=3)[NH:31][C:30]=2B2OC(C)(C)C(C)(C)O2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>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:23]1([C:29]2[C:37]3[C:32](=[CH:33][C:34]([C:38]([O:40][CH3:41])=[O:39])=[CH:35][CH:36]=3)[NH:31][C:30]=2[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[S:8][CH2:9][CH2:10][O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 23152432methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylateHCID 231526382-[2-(2-Bromophenylsulfanyl)ethoxy]tetrahydropyran

Product 1

HCID 11995000methyl 3-cyclohexyl-2-{2-[2-(tetrahydropyran-2-yloxy)ethylsulfanyl]phenyl}-1H-indole-6-carboxylateYield 87.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a suspension of 2-[2-(2-bromophenylsulfanyl)ethoxy]tetrahydropyran (1.00 g, 3.2 mmol), sodium hydrogen carbonate (1.10 g, 13.2 mmol) and tetrakis(triphenylphosphine)palladium (363 mg, 0.310 mmol) in 1,2-dimethoxyethane (10 ml) and water (5 ml) was added methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate (1.45 g, 3.78 mmol) with heating under reflux and the mixture was heated under reflux for 2.5 hr. The reaction mixture was allowed to cool to room temperature, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and 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=5:1-3:1) to give methyl 3-cyclohexyl-2-{2-[2-(tetrahydropyran-2-yloxy)ethylsulfanyl]phenyl}-1H-indole-6-carboxylate (1.38 g, yield 74.5%).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 2.5 hr
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was successively washed with water and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationAfter filtration
  9. customthe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel chromatography (hexane:ethyl acetate=5:1-3:1)

Sources & evidence

ORD record
ord-75d4225e3d924076bf126982453527a0
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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