反应详情

Under a nitrogen atmosphere, KF (0.28 g, 1.87 mmol) and 18-crown-6 (0.49 g, 1.87 mmol) were added to a solution of (3R)-1-[(1R)-1-(4-methoxyphenyl)ethyl]-5-oxopyrrolidine-3-carbaldehyde 1.07 (420 mg, 1.7 mmol) and (difluoromethyl)trimethylsilane (530 mg, 0.52 mmol, 68 uL), and the mixture was stirred at room temperature for 5 hours. 1M HCl was added, and the reaction was stirred for 15 minutes. EtOAc and water were added and the aqueous layer was extracted with EtOAc. The combined organics were dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (0→15% MeOH in EtOAc) to afford 4-(2,2-difluoro-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 1.24 as a mixture of diastereomers, which were not separated at this stage.

1. stirringthe reaction was stirred for 15 minutes
2. extractionthe aqueous layer was extracted with EtOAc
3. dry with materialThe combined organics were dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by flash chromatography (0→15% MeOH in EtOAc)