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

HRID 705599Notes

Reaction equation

HRID 705599 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][C:15](=O)[N:16]2OC)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22](=[O:25])([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:43])C>CC#N>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:43][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:25][CH3:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 10796Cesium carbonateHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 69329959HCID 69329959, compound

Product 1

HCID 229354107-(Benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolineYield 41%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 7-Benzyloxy-methoxy-1H-quinolinone (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-36c93259471d46d5bb855226f07826b3
Source dataset
uspto-grants-2015_11
Patent number
US09174947B2

Reaction notes

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