Cesium carbonate → 7-(Benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinoline

HRID 15514Notes

Reaction equation

HRID 15514 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=[O:19])[CH:14]=[CH:15][NH:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:28][C:29]1[CH:30]=[C:31]([N+:36]([O-:38])=[O:37])[CH:32]=[CH:33][C:34]=1F>CN(C=O)C.CC#N>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:34]3[CH:33]=[CH:32][C:31]([N+:36]([O-:38])=[O:37])=[CH:30][C:29]=3[F:28])=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 226465797-(Benzyloxy)-6-methoxyquinolin-4-ol

Product 1

HCID 229354107-(Benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolineYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 7-(benzyloxy)-6-methoxyquinolin-4(1H)-one (4.4 g, 15.6 mmol), Cs2CO3 (9.0 g) in DMF (40 mL) and CH3CN (40 mL) was stirred for 30 minutes at rt. To this mixture was added 3,4-difluoronitrobenzene (2.5 g, 15.7 mmol), and the reaction mixture was stirred at rt overnight. The reaction product was a mixture of O- and N-alkylation products. It was mostly concentrated in vacuo, EtOAc (200 mL) and water (50 mL) were added to the residue, EtOAc layer was separated, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with hexane:EtOAc:MeOH/800:200:40, and then 700:300:40 to obtain the desired O-alkylation product (3.0 mg, 46%) as a white solid. 1H NMR (CDCl3) δ 8.73 (d, 1H, J=6.0 Hz), 8.29-8.26 (m, 2H), 8.08 (s, 1H), 7.60-7.35 (m, 7H), 6.67 (d, 1H, J=6.6 Hz), 5.42 (s, 2H), 4.10 (s, 3H); MS(ESI+) m/z 421.3 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at rt overnight
  2. additiona mixture of O- and N-alkylation products
  3. concentrationIt was mostly concentrated in vacuo, EtOAc (200 mL) and water (50 mL)
  4. additionwere added to the residue, EtOAc layer
  5. customwas separated
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-53f3a8859bef4310abbe4cc2d5d65160
Source dataset
uspto-grants-2010_06
Patent number
US07732613B2

Reaction notes

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