Propionamide → HCID 86703360, compound

Participants

Reaction Conditions

Reaction Steps

A solution of Example A1 (35 g, 122 mmol) in anhydrous 1,4-dioxane (900 mL) was degassed with nitrogen for 10 min and to it was added propionamide (10.5 g, 143 mmol), 1,1′-bis(diphenylphosphino) ferrocene (dppf, 6.6 g, 12.0 mmol, 0.1 equiv.), Cs2CO3 (58.4 g, 179 mmol) and Pd2(dba)3 (5.47 g, 5.97 mmol). The mixture was degassed with nitrogen for another 15 min and then heated to 85° C. (internal temp) and stirred at that temp for 4 h. The reaction mixture was cooled to RT, filtered through a bed of diatomaceous earth and washed with EtOAc (1 L). The combined filtrates were concentrated under reduced pressure and purified by a silica gel chromatography (EtOAc/hexanes) to afford 30 g. This material was further purified by a trituration with diisopropyl ether (600 mL) and drying under vacuum at 40° C. to provide N-(4-(2,5-difluoro-4-nitrophenoxy)pyridin-2-yl)propionamide (27.2 g, 69% yield). MS (ESI): m/z 324.1 (M+H+). This material was carried to next step without further purification.

Provenance & Evidence