Dimethylformamide → 2-(Difluoromethyl)-4-(2-morpholinoethoxy)benzaldehyde

Participants

Reaction Steps

To a solution of 4-(2-(4-bromo-3-(difluoromethyl)phenoxy)ethyl)morpholine (123; 2.8 g, 8.38 mmol) in THF (90 mL) was added n-BuLi (1.6 M solution in hexanes, 7 mL, 11.2 mmol) at −78° C. The resulting reaction mixture was stirred at the same temperature for 1 h and DMF (1.24 g, 17 mmol) was added dropwise. After stirring the mixture at −78° C. for an additional 30 min, saturated aqueous NH4Cl was added and the mixture was extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography afforded 2-(difluoromethyl)-4-(2-morpholinoethoxy)benzaldehyde 124 (1.6 g, 67%) as a brown yellow oil.

Provenance & Evidence