Potassium Carbonate → tert-butyl cyclopropyl{[1-(3-methoxypropyl)-4-methyl-1H-indol-3-yl]methyl}carbamate

HRID 872030Notes

Reaction equation

HRID 872030 reaction equation
[C:1](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1.Br[C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[C:19]([CH2:31][N:32]([CH:40]1[CH2:42][CH2:41]1)[C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:20][N:21]2[CH2:26][CH2:27][CH2:28][O:29][CH3:30]>O1CCOCC1.O.Cl[Pd]Cl.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:40]1([N:32]([CH2:31][C:19]2[C:18]3[C:22](=[CH:23][CH:24]=[CH:25][C:17]=3[CH3:1])[N:21]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[CH:20]=2)[C:33](=[O:39])[O:34][C:35]([CH3:36])([CH3:37])[CH3:38])[CH2:42][CH2:41]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 86645632tert-butyl {[4-bromo-1-(3-methoxypropyl)-1H-indol-3-yl]methyl}cyclopropylcarbamate

Product 1

HCID 59494370tert-butyl cyclopropyl{[1-(3-methoxypropyl)-4-methyl-1H-indol-3-yl]methyl}carbamateYield 96.9%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Potassium carbonate (207 mg), trimethylboroxin (175 μL) and bis(diphenylphosphino)ferrocene dichloropalladium (II) (40.8 mg) were added to a solution of tert-butyl {[4-bromo-1-(3-methoxypropyl)-1H-indol-3-yl]methyl}cyclopropylcarbamate (218 mg) in 1,4-dioxane (14.5 ml) and the mixture was stirred at 110° C. under argon atmosphere for 4 hours. After being cooled to room temperature, the reaction mixture was diluted with water and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated brine successively, dried over magnesium sulfate and concentrated in vacuo. The resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane to n-hexane/ethyl acetate=1/1 to 1/4) to give tert-butyl cyclopropyl{[1-(3-methoxypropyl)-4-methyl-1H-indol-3-yl]methyl}carbamate (180 mg) as a yellow oil.

Workup

  1. temperatureAfter being cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate and saturated brine successively
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane to n-hexane/ethyl acetate=1/1 to 1/4)

Sources & evidence

ORD record
ord-ff345c2f7d9a45e0a29754dc556065ba
Source dataset
uspto-grants-2015_03
Patent number
US08975252B2

Reaction notes

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