Cesium carbonate → HCID 66691509, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence