Cesium carbonate → Methyl 5-(difluoromethoxy)picolinate

Participants

Reaction Conditions

Reaction Steps

To a RBF were added 5-hydroxy-2-pyridinecarboxylic acid methyl ester (1.2 ml, 9.94 mmol), sodium chlorodifluoroacetate (3.3 g, 21.54 mmol), and cesium carbonate (9.7 g, 29.8 mmol) in DMF (20 ml). The reaction mixture was heated to 100° C. for 3 h. Then it was cooled to RT. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with water, brine and dried over MgSO4. It was filtered and concentrated. The crude product was purified by flash chromatography eluting with a gradient of 5% to 50% EtOAc in hexane, to provide methyl 5-(difluoromethoxy)picolinate (1.4962 g, 7.37 mmol, 74.1% yield). MS m/z: 204.3 [M+H].

Provenance & Evidence