反应详情

An aqueous NaOH 2N (2.55 ml, 5.10 mmol) solution was added to methyl 8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylate (0.79 g, 1.68 mmol) in a mixture of MeOH (9 mL) and DCM (6 mL) and the reaction mixture was stirred at room temperature overnight. The mixture was cooled to 0° C. and an aqueous HCl 2N (2.5 mL, 5.0 mmol) solution was added dropwise to the reaction mixture until pH ˜3. After dilution with water (9 mL), the reaction mixture was concentrated to half volume. The aqueous phase was extracted with DCM, the organic phase was concentrated to dryness, leading to a foam, which was triturated in EtAc, collected by filtration, washed with EtAc, diethyl ether, dried under vacuum at 50° C. to afford 8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylic acid (0.638 g, 83%) as an off-white solid. Mass Spectrum: m/z [M+H]+=457.

1. temperatureThe mixture was cooled to 0° C.
2. concentrationAfter dilution with water (9 mL), the reaction mixture was concentrated to half volume
3. extractionThe aqueous phase was extracted with DCM
4. concentrationthe organic phase was concentrated to dryness
5. customwas triturated in EtAc
6. filtrationcollected by filtration
7. washwashed with EtAc, diethyl ether
8. customdried under vacuum at 50° C.