Hydrochloric Acid → 1-benzyl-6-(3-chlorophenyl)-1H-indole

HRID 2221230Notes

Reaction equation

HRID 2221230 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.[CH2:11]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24](Br)[CH:25]=2)[CH:20]=[CH:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:11]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[CH:25]=2)[CH:20]=[CH:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 2734323(3-Chlorophenyl)boronic acidHCID 220329571-benzyl-6-bromo-1H-indole

Product 1

HCID 220329421-benzyl-6-(3-chlorophenyl)-1H-indoleYield 50%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

3-Chlorophenylboronic acid (1.21 g, 7.76 mmol) was added in four portions to the mixture of 1-benzyl-6-bromo-1H-indole (1.12 g, 3.91 mmol), palladium (II) acetate (0.0191 g, 0,0850 mmol), and tetrabutylammonium bromide (1.26 g, 3.91 mmol) in water (22.5 mL) and THF (2.5 mL) while heating at 70° C. for 4 hours. The reaction mixture was allowed to cool to room temperature and 2N hydrochloric acid was slowly added. The mixture was extracted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was purified by flash chromatography (Biotage apparatus) using 0-100% ethyl acetate in hexane as an eluant. Drying at 60° C. for 40 minutes yielded (0.621 g, 50%) of 1-benzyl-6-(3-chlorophenyl)-1H-indole as a yellow gum. Mass spectrum (+ESI, [M+H]+) m/z 318; 1HNMR (500 MHz, DMSO-d6): δ 7.85 (s, 1H), 7.75 (t, 1H, J=1.8 Hz), 7.6-7.65 (m, 2H), 7.55(d, 1H, J=3.1 Hz), 7.45 (t, 1H, J=7.8 Hz), 7.25-7.35 (m, 4H), 7.2-7.25 (m, 3H), 6.5 (d, 1H, J=3.1 Hz), and 5.5 ppm (s, 2H). Elemental Analysis for C21H16ClN: Calculated: C, 79.36; H, 5.07; N, 4.41. Found: C, 79.32; H, 5.21; N, 4.28.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography (Biotage apparatus)
  8. customDrying at 60° C. for 40 minutes

Sources & evidence

ORD record
ord-ff8fb5e490554f9ea23fbc75caece653
Source dataset
uspto-grants-2008_05
Patent number
US07368471B2

Reaction notes

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