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

HRID 1791459Notes

Reaction equation

HRID 1791459 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 poritions 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).

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-d9ca3800bde84f2ebc65ce5c07792f8f
Source dataset
uspto-grants-2006_07
Patent number
US07074817B2

Reaction notes

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