Dimethylformamide → 4-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline

HRID 1517881Notes

Reaction equation

HRID 1517881 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[OH:15].C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C.F[C:28]1[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][C:29]=1[F:37]>CC#N>[F:37][C:29]1[CH:30]=[C:31]([N+:34]([O-:36])=[O:35])[CH:32]=[CH:33][C:28]=1[O:15][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 178486804HCID 178486804, compound

Product 1

HCID 114507634-(2-Fluoro-4-nitrophenoxy)-6,7-dimethoxyquinolineYield 51.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 6,7-dimethoxyquinolin-4-ol (50 g, 0.244 mol) and Cs2CO3 (159 g, 0.488 mol) in CH3CN (300 mL)/DMF (300 mL) was stirred at room temperature for 30 min. 1,2-Difluoro-4-nitrobenzene (42.7 g, 0.268 mol) was then added dropwise. After stirring at rt for 3.5 h, the reaction solution was concentrated in vacuo. Ice (500 mL) was added to the residual suspension and the mixture was stirred overnight for precipitation. The solid was collected by filtration and further purified by a silica gel column chromatography (EtOAc) to give the title compound as a pale yellow powder (43.1 g, 51.2%).

Workup

  1. concentrationthe reaction solution was concentrated in vacuo
  2. additionIce (500 mL) was added to the residual suspension
  3. stirringthe mixture was stirred overnight for precipitation
  4. filtrationThe solid was collected by filtration
  5. customfurther purified by a silica gel column chromatography (EtOAc)

Sources & evidence

ORD record
ord-9dc3add691324930af89651c08aaecd9
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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