Dimethylformamide → (S)-2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzaldehyde

Participants

Reaction Steps

To a solution of (S)-4-((4-bromo-3-(difluoromethyl)phenoxy)methyl)-2,2-dimethyl-1,3-dioxolane (65; 3 g, 0.089 mol) in THF (30 ml) was added n-BuLi (2.5M solution in hexane, 3.9 ml, 0.097 mol) at −78° C. The mixture was stirred at the same temperature for 1 h and DMF (0.929 g, 0.103 mol) was added dropwise. After stirring at −78° C. for an additional 20 min, saturated aqueous NH4Cl (30 ml) was added. The resulting reaction mixture was warmed to room temperature and extracted with Et2O (3×15 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by chromatography (petroleum ether/EtOAc=5:1) to afford the titled compound, namely (S)-2-(difluoromethyl)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzaldehyde 66 (1.83 g, 72%).

Provenance & Evidence