Cesium carbonate → HCID 66691509, compound

HRID 1697871Notes

Reaction equation

HRID 1697871 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][C:16]3([C:19]([O:21][CH3:22])=[O:20])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].F[C:30]1[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][C:31]=1[F:39]>C(#N)C.CN(C=O)C.CCOC(C)=O.O>[F:39][C:31]1[CH:32]=[C:33]([N+:36]([O-:38])=[O:37])[CH:34]=[CH:35][C:30]=1[O:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][C:16]3([C:19]([O:21][CH3:22])=[O:20])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 178498907HCID 178498907, compound

Product 1

HCID 66691509HCID 66691509, compound

Reagents, catalysts & solvents 2

HCID 21891449acetonitrile N,N-dimethylformamideSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 1-((4-hydroxy-6-methoxyquinolin-7- yloxy)methyl)cyclopropanecarboxylate (600 mg, from Example 1) was mixed with Cs2CO3 (2 eq) and 1,2-difluoro-4-nitrobenzene (1.2 eq) in acetonitrile/DMF (20 ml, 1/1). The reaction was heated at 60° C. for 1 hour and diluted with EtOAc/H2O then extracted with EtOAc three times. The combined organic layer was dried, evaporated and purified with silica gel column to give methyl 1-((4-(2-fluoro-4-nitro-phenoxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropanecarboxylate (300 mg). This product was mixed with iron powder (300 mg) and NH4Cl (30 mg) in EtOH/H2O (20 ml, 9/1). The reaction was refluxed for 3 hours and filtered through Celite followed by evaporation. The residue was mixed with EtOAc/H2O and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried. The solution was evaporated and purified with silica gel column to give methyl 1-((4-(2-fluoro-4-amino-phenoxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropanecarboxylate (150 mg).

Workup

  1. extractionthen extracted with EtOAc three times
  2. customThe combined organic layer was dried
  3. customevaporated
  4. custompurified with silica gel column

Sources & evidence

ORD record
ord-465793933ff54b0f952b70560b9a12ab
Source dataset
uspto-grants-2012_04
Patent number
US08163923B2

Reaction notes

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