Sodium hydride → 8-Fluoro-4-[2-(4-methylphenyl)ethoxy]quinoline

HRID 1196477Notes

Reaction equation

HRID 1196477 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][OH:12])=[CH:6][CH:5]=1.[Cl:13][C:14]1[C:23]2[C:18](=[C:19]([F:24])[CH:20]=[CH:21][CH:22]=2)[N:17]=[CH:16][CH:15]=1>CN(C=O)C.O>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]2[C:18]=1[N:17]=[CH:16][CH:15]=[C:14]2[O:12][CH2:11][CH2:10][C:7]1[CH:8]=[CH:9][C:4]([CH3:3])=[CH:5][CH:6]=1.[Cl:13][C:14]1[C:23]2[C:18](=[C:19]([O:12][CH2:11][CH2:10][C:7]3[CH:8]=[CH:9][C:4]([CH3:3])=[CH:5][CH:6]=3)[CH:20]=[CH:21][CH:22]=2)[N:17]=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 952944-Methylphenethyl alcoholHCID 27365874-Chloro-8-fluoroquinoline

Product 2

HCID 1641888-Fluoro-4-[2-(4-methylphenyl)ethoxy]quinolineYield 52.8%HCID 19094098HCID 19094098, compoundYield 8.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.2 g of sodium hydride in 50 ml of DMF was added 3.4 g of 2-(4-methylphenyl)ethanol, and the mixture was stirred for one hour at room temperature. Then 4.5 g of 4-chloro-8-fluoroquinoline were added, the mixture was heated to reflux for five hours, and then cooled to room temperature, and poured into a mixture of ice in water. The solid phase was collected and dried. TLC showed three products. These were separated by HPLC (silica gel, 70% pentane/30% EtOAc) giving 1.84 g of 8-fluoro-4-[2-(4-methylphenyl)ethoxy]quinoline (Yield: 26.3%; M.P. 89°-90° C.) 0.610 g of 4-chloro-8-[2-(4-methylphenyl)ethoxy]quinoline (Yield: 8.7%; M.P. 74°-75° C.); and 0.450 g of 4,8-bis[2-(4-methylphenyl)ethoxy]quinoline (Yield: 6.4%; M.P. 142°-143° C).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for five hours
  3. temperaturecooled to room temperature
  4. customThe solid phase was collected
  5. customdried
  6. customThese were separated by HPLC (silica gel, 70% pentane/30% EtOAc)

Sources & evidence

ORD record
ord-d2ffb9298bd2440ebf7511d8e3d043fd
Source dataset
uspto-grants-1992_05
Patent number
US05114939

Reaction notes

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