Hydrochloric Acid → HCID 49848228, compound

Participants

Reaction Steps

To a 50 mL round bottom flask adapted for magnetic stirring and fitted with a nitrogen inlet tube is charged 5-(3-fluorophenyl)-3-hydroxypyridine-2-carboxylic acid, 10, (0.932 gm, 4 mmol), N,N′-carbonyldiimidazole (CDI) (0.97 g, 6 mmol) and dimethyl sulfoxide (5 mL). The reaction mixture is stirred at 45° C. for about 1 hour then cooled to room temperature. Glycine methyl ester hydrochloride (1.15 g, 12 mmol) is added followed by the dropwise addition of diisopropylethylamine (3.2 mL, 19 mmol). The mixture is then stirred for 2.5 hours at room temperature after which water (70 mL) is added. The contents of the reaction flask is cooled to 0° C. to 5° C. and 1N HCl is added until the solution pH is approximately 2. The solution is extracted with dichloromethane (100 mL) and the organic layer dried over MgSO4 for 16 hours. Silica gel (3 g) is added and the solution slurried for 2 hours after which the solids are removed by filtration. The filtrate is concentrated to dryness under reduced pressure and the resulting residue is slurried in methanol (10 mL) for two hours. The resulting solid is collected by filtration and washed with cold methanol (20 mL) then hexane and the resulting cake is dried to afford the desired product.

Provenance & Evidence