151103-08-1

1514-87-0

139-85-5

151103-08-1

Example 10 Preparation of 4-difluoromethoxy-3-hydroxybenzaldehyde: 3,4-dihydroxybenzaldehyde (0.50 g, 3.62 mmol, Aldrich), methyl 2-chloro-2,2-difluoroacetate (0.52 g, 3.62 mmol, Aldrich), and potassium carbonate (0.50 g, 3.62 mmol) were placed in argon- protected DMF ( 5.0 mL). The reaction mixture was stirred at 60°C to 65°C for 3 hours. Upon completion of the reaction, the DMF was removed by distillation under reduced pressure. the residue was subjected to liquid-liquid partitioning with 3N HCl aqueous solution and ether. The aqueous phase was extracted three times with ether. The combined organic phases were washed sequentially with water and saturated saline, dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by fast column chromatography (silica gel, 25% ethyl acetate/hexane) to afford the title compound 4-difluoromethoxy-3-hydroxybenzaldehyde as a white solid (0.20 g, 38% yield). Melting point 83°C to 85°C.