Hydrochloric Acid → 5-Benzyloxy-1-(4-fluoro-phenyl)-1H-indole

HRID 1633613Notes

Reaction equation

HRID 1633613 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1.[OH-].[K+].Cl>O.CCOCC>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)[CH:13]=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 99931-Bromo-4-fluorobenzeneHCID 146245-BenzyloxyindoleHCID 14797Potassium Hydroxide

Product 1

HCID 111979085-Benzyloxy-1-(4-fluoro-phenyl)-1H-indoleYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

To 22.3 g (0.1 mol) 5-benzyloxyindole in 110 ml (1.0 mol) 1-bromo-4-fluorobenzene were added 28 g (0.5 mol) powdered potassium hydroxide and 6.4 g (0.1 mol) Cu as powder. The suspension was heated to reflux for 2 h. At RT, ether and water were added, the mixture was acidified with 2M HCl and extracted with ether. The combined organic phases were washed with water and dried over Na2SO4. Column chromatography on silica gel with a gradient hexane-hexane/EtOAc 19:1-9:1 yielded 19 g (60%) 5-Benzyloxy-1-(4-fluoro-phenyl)-1H-indole as colorless solid, MS: 318 (MH+).

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 2 h
  3. extractionextracted with ether
  4. washThe combined organic phases were washed with water
  5. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-fd7faa6e24e940f88ed73fa8112c5f67
Source dataset
uspto-grants-2003_01
Patent number
US06503907B2

Reaction notes

Loading…