反应详情

To a solution of [5-(4-fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid methyl ester (prepared above, 82 mg, 0.269 mmol) in THF/methanol (6 mL/0.3 mL) was added 1 N NaOH (0.3 mL, 0.3 mmol). Additional 1 N NaOH aliquots were added after 5 min (0.15 mL), 25 min (0.25 mL), and 2 h (1.0 mL). By thin layer chromatography (15/84/1 methanol/dichloromethane/acetic acid) it appeared that the starting material never disappeared, but LC/MS showed the presence of mostly methyl ether, with some desired acid and no starting material. The reaction mass was extracted with ethyl acetate. The combined organic layers were washed 1× with water, then 2× with 5% NaHCO3. The aqueous layers were combined, acidified to pH 1 with 3% HCl and extracted with dichloromethane. The organic layers were combined, washed with brine, dried and concentrated in vacuo to afford 12.8 mg (16% yield) of the titled carboxylic acid as a white solid. ESI-MS m/z 292 (MH+), 290 (M−H)−.

1. extractionThe reaction mass was extracted with ethyl acetate
2. washThe combined organic layers were washed 1× with water
3. extractionextracted with dichloromethane
4. washwashed with brine
5. customdried
6. concentrationconcentrated in vacuo