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

HRID 2106087Notes

Reaction equation

HRID 2106087 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[C:29]1[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:30]=1[F:38]>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:29]3[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][C:30]=3[F:38])=[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 41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent2×

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 7-Benzyloxy-6-methoxy-1H-quinolin-4-one (12.2 g, 43.3 mmol, 1.0 eq.), acetonitrile (150 ml), DMF (150 ml) and cesium carbonate (28.2 g, 86.5 mmol, 2.0 eq). The mixture was stirred at room temperature for 30 minutes at which time 1,2-difluoro-4-nitro-benzene (7.57 g, 47.6 mmol, 1.1 eq) was added over a 10 minute period. After 2 hours the reaction was complete at which time 75% of the MeCN and DMF was removed and the resulting solution was poured over into ice water. The solid was filtered and dried and further columned with a biotage system. The eluent was 1:3 ethyl acetate/hexane. Removal of the solvent afforded 7-Benzyloxy-4-(2-fluoro-4-nitro-phenoxy)-6-methoxy-quinoline as a pale green solid (7.4 g, 41% yield). 1H NMR (400 MHz, CDCl3): 8.53 (d, 1H), 8.42 (dd, 1H), 8.16 (m, 1H), 7.5 (m, 8H), 6.76 (d, 1H), 5.31 (s, 2H), 3.92 (s, 3H); MS (EI) for C23H27FN2O5: 421 (MH+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. additionwas added over a 10 minute period
  3. customwas removed
  4. additionthe resulting solution was poured over into ice water
  5. filtrationThe solid was filtered
  6. customdried
  7. customRemoval of the solvent

Sources & evidence

ORD record
ord-f494cd925bd349d892532df9b332e188
Source dataset
uspto-grants-2009_08
Patent number
US07579473B2

Reaction notes

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