tert-Butyl (2S)-4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate → 1,1-Dimethylethyl (2S)-4,4-difluoro-2-formyl-1-pyrrolidinecarboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][C@H:9]1[CH2:15][OH:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:13])([F:14])[CH2:10][C@H:9]1[CH:15]=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]Participants
4
Procedure
To a solution of Compound 2b (1.33 g; 5.61 mmol) in CH2Cl2 (20 mL) was added 3,3,3-triacetoxy-3-iodophthalide (3.56 g; 8.39 mmol) at ambient temperature. The reaction mixture was stirred at room temperature for 2 h. The resultant mixture was diluted with EtOAc, and washed sequentially with saturated NaHCO3 (aq) and H2O. The organic phase was washed with H2O, and then dried over Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 2c (0.58 g; 44% yield) as a colorless oil. 1H-NMR (400 MHz, CDCl3): δ 9.59 (d, 1H), 4.28-4.45 (m, 1H), 3.77-3.89 (m, 2H), 2.43-2.63 (m, 2H), 1.46-1.51 (m, 9H).