874822-98-7

122433-52-7

874822-98-7

General procedure for the synthesis of 5-fluoro-3-hydroxymethyl-2-methoxypyridine from 5-fluoro-2-methoxynicotinic acid methyl ester: To a 200 mL tetrahydrofuran solution of 5-fluoro-2-methoxynicotinic acid methyl ester (35, 10 g, 54.0 mmol) was added slowly and dropwise to lithium aluminum hydroxide (81 mL, 1 M solution in tetrahydrofuran, 81 mmol) at -78 °C. The reaction temperature was maintained at -78 °C and stirred for several hours. Upon completion of the reaction, 3 mL of water, 3 mL of 15% aqueous sodium hydroxide solution and 10 mL of water were added dropwise to quench the reaction. Subsequently, 200 mL of methyl tert-butyl ether was added for dilution. The solid insoluble material was removed by filtration and the filtrate was concentrated under vacuum to afford the target compound 5-fluoro-3-hydroxymethyl-2-methoxypyridine (36, 8 g, 50.9 mmol, 94% yield) as a white solid.