Benzyl Bromide → 1-benzyl-3-methyl-2-pyridin-3-yl-1H-indole

HRID 593496Notes

Reaction equation

HRID 593496 reaction equation
Cl.[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[CH2:28]([N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:3]([CH3:2])=[C:4]1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 7498Benzyl Bromide2×HCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539613-Methyl-2-(3-pyridyl)indole hydrochloride

Product 1

HCID 445541311-benzyl-3-methyl-2-pyridin-3-yl-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-Methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 1, 0.110 g, 0.445 mmol) is suspended in THF (3 mL) and cooled to 0° C. KHMDS (0.5M in toluene, 2 mL, 1 mmol) is added dropwise, the cooling bath is lowered and the mixture is stirred at room temperature for 15 min, whereupon it is lowered in the ice-water bath. Benzyl bromide (0.093 g, 0.534 mmol) is added dropwise. After 3 h, additional benzyl bromide (0.046 g, 0.267 mmol) is added, and upon reaction completion, the mixture is quenched with 1M aqueous HCl and diluted with ethyl acetate. The aqueous phase is extracted and the combined organic phase is dried over MgSO4, filtered and concentrated in vacuo. Purification of the residue by silica gel flash chromatography (dichloromethane-methanol, 99:1) affords 1-benzyl-3-methyl-2-pyridin-3-yl-1H-indole as a pale yellow solid. 1H NMR (400 MHz, MeOD) δ ppm 2.18 (s, 3H), 5.19 (s, 2H), 6.69-6.71 (m, 2H), 7.01-7.11 (m, 5H), 7.21 (d, J=8.1 Hz, 1H), 7.37-7.41 (m, 1H), 7.52 (d, J=7.8 Hz, 1H), 7.67-7.70 (m, 1H), 8.36 (s, 1H), 8.43-8.45 (m, 1H). MS (ESI) m/z 299 (M+H)+.

Workup

  1. waitAfter 3 h
  2. customupon reaction completion
  3. customthe mixture is quenched with 1M aqueous HCl
  4. additiondiluted with ethyl acetate
  5. extractionThe aqueous phase is extracted
  6. dry with materialthe combined organic phase is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by silica gel flash chromatography (dichloromethane-methanol, 99:1)

Sources & evidence

ORD record
ord-40799046429f4403ba291e68aee30771
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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