Sodium Carbonate → methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1012246Notes

Reaction equation

HRID 1012246 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.[CH3:21][O:22][CH2:23][O:24][C:25]1[CH:30]=[C:29]([O:31][CH2:32][O:33][CH3:34])[CH:28]=[CH:27][C:26]=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>[CH3:34][O:33][CH2:32][O:31][C:29]1[CH:30]=[C:25]([O:24][CH2:23][O:22][CH3:21])[CH:26]=[CH:27][C:28]=1[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

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylateHCID 223378172,4-Bis(methoxymethoxy)phenylboronic acid

Product 1

HCID 11995225methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-indole-6-carboxylateYield 86.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a suspension of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (14.5 g, 43.2 mmol), obtained in the same manner as in the method described in WO03/010140, and 2,4-bismethoxymethoxyphenylboronic acid (13.6 g, 56.2 mmol) in 1,2-dimethoxyethane (140 ml) and water (70 ml) were added lithium chloride (5.5 g, 129 mmol), sodium carbonate (13.7 g, 129 mmol) and tetrakis(triphenylphosphine)palladium (5.0 g, 4.3 mmol), and the mixture was stirred at 90° C. for 22 hr. The mixture was allowed to cool to room temperature, and filtered through celite. The filtrate was extracted with ethyl acetate and the organic layer was washed successively with saturated aqueous ammonium chloride solution and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=3:1) to give methyl 2-(2,4-bismethoxymethoxyphenyl)-3-cyclohexyl-1H-indole-6-carboxylate (16.9 g, yield 86%).

Workup

  1. customobtained in the same manner as in the method
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. extractionThe filtrate was extracted with ethyl acetate
  5. washthe organic layer was washed successively with saturated aqueous ammonium chloride solution and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customthe obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-1f97fac0e254406ba2c0530f2899a7e6
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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