Sodium Carbonate → methyl 2-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1012258Notes

Reaction equation

HRID 1012258 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.[C:21]([O:25][C:26]([N:28]1[CH:32]=[CH:31][CH:30]=[C:29]1B(O)O)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>C(COC)OC.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>[C:21]([O:25][C:26]([N:28]1[CH:32]=[CH:31][CH:30]=[C:29]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)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 23152766methyl 2-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-cyclohexyl-1H-indole-6-carboxylateYield 64%

Reagents, catalysts & solvents 3

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

Procedure

To a suspension of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (800 mg, 2.38 mmol) obtained in the same manner as in the method described in WO03/010140 and N-tert-butoxycarbonylpyrrole-2-boronic acid (1.00 g, 4.76 mmol) in dimethoxyethane (10 ml) and water (5 ml) were added sodium carbonate (757 mg, 7.14 mmol), lithium chloride (202 mg, 4.76 mmol) and tetrakis(triphenylphosphine)palladium (275 mg, 0.238 mmol), and the mixture was heated under reflux for 9 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 washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate=8:1-6:1) to give methyl 2-(1-tert-butoxycarbonyl-1H-pyrrol-2-yl)-3-cyclohexyl-1H-indole-6-carboxylate (642 mg, yield 64%).

Workup

  1. customobtained in the same manner as in the method
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 9 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate 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 residue was purified by silica gel chromatography (hexane:ethyl acetate=8:1-6:1)

Sources & evidence

ORD record
ord-3132eff5d5344c7aa9f6190e5171bd4c
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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