Sodium Carbonate → 5-Phenyl-3-(1-methylpiperidin-4-yl)-1-(triisopropylsilyl)-indole

HRID 278011Notes

Reaction equation

HRID 278011 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:6]=[C:5]2[CH:21]1[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Cl-].[Na+].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:28]1([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:6]=[C:5]3[CH:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 120859685-Bromo-3-(1-Methylpiperidin-4-yl)-1-Triisopropylsilylindole

Product 1

HCID 226267975-Phenyl-3-(1-methylpiperidin-4-yl)-1-(triisopropylsilyl)-indoleYield 22%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 5-bromo-3-(1-methylpiperidin-4-yl)-1-(triisopropylsilyl)-indole (0.600 g, 1.34 mmol), phenylboronic acid (0.171 g, 1.40 mmol), tetrakis(triphenylphosphine)palladium(0) (0.077 g, 0.067 mmol), and 2M aqueous sodium carbonate solution (2 mL) in toluene (15 mL) was heated at reflux overnight. The solution was allowed to cool to room temperature, diluted with ethyl acetate and brine, the organic phase was separated, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel (flash) chromatography (dichloromethane:methanol:aqueous ammonium hydroxide 4.5:0.5:0.2) to give 0.128 g of 5-phenyl-3-(1-methylpiperidin-4-yl)-1-(triisopropylsilyl)-indole (22%) as an oil, which was desilylated by dissolving in 1 mL of tetrahydrofuran and treating with tetrabutylammonium fluoride (1M solution in tetrahydrofuran, 4 mL) with stirring at room temperature for 3 hours. The mixture was concentrated in vacuuo, and the resulting oil was purified by silica gel (flash) chromatography (eluting with 500 mL dichloromethane, followed by dichloromethane:methanol:aqueous ammonium hydroxide 4.5:0.5:0.1) to give the title compound (0.045 g) as an amorphous white solid. FDMS m/e=289 (M+). EA calculated for C20H22N2: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.19; H, 7.37; N, 9.75.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. customthe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel (flash) chromatography (dichloromethane:methanol:aqueous ammonium hydroxide 4.5:0.5:0.2)

Sources & evidence

ORD record
ord-ba5a45cc4a9d4453a900cca0044f5da5
Source dataset
uspto-grants-2002_03
Patent number
US06358972B1

Reaction notes

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