Phenol → 8-Bromo-2-phenoxyquinoline

HRID 1055991Notes

Reaction equation

HRID 1055991 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18](Cl)[CH:17]=[CH:16]2>C1COCC1>[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18]([O:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[CH:17]=[CH:16]2

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 109557558-Bromo-2-chloroquinoline

Product 1

HCID 897820178-Bromo-2-phenoxyquinolineYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

NaH (60% w/w in mineral oil; 1.311 g, 32.8 mmol) was added to a solution of phenol (3.09 g, 32.8 mmol, Aldrich) in THF (219 ml) at 0° C.; the resulting mixture was stirred for 10 min before 8-bromo-2-chloroquinoline (178a, 5.30 g, 21.86 mmol, Biofine International, Inc., Vancouver, BC) in THF (100 ml) was added. The reaction was stirred at 0° C. for 1 h before it was warmed to RT and stirred for 3 h, then heated at reflux for 24 h. Purification by silica gel chromatography (100% hexanes to 10% EtOAc/hexanes) provided 8-bromo-2-phenoxyquinoline (178b, 41% yield) as a light yellow oil. MS (ESI, pos. ion) m/z: 300.0/302 (M+1).

Workup

  1. additionwas added
  2. temperaturewas warmed to RT
  3. stirringstirred for 3 h
  4. temperatureheated
  5. temperatureat reflux for 24 h
  6. customPurification by silica gel chromatography (100% hexanes to 10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-22e07c2dbdfb4c0eb385aa8f7746eb17
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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