反应详情

To a stirred solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (1.1 g, 4.37 mmol) (as prepared in Ex. 2, Part A) in anhydrous DMF (10 mL) cooled to 0° C. was added HOBT (1.339 g, 8.74 mmol), EDC (1.257 g, 6.56 mmol), DIEA (3.05 mL, 17.49 mmol) followed by ammonium chloride (1.169 g, 21.86 mmol). The reaction mixture was allowed to warm to RT and stirred for 12 h under a nitrogen atmosphere. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)nicotinamide (0.900 g, 3.59 mmol, 82% yield) LC/MS (ESI) m/e 251 [(M+H)+, calcd for C12H9ClFN2O 251]; LC/MS retention time (method A): tR=1.34 min.

1. extractionextracted with ethyl acetate (2×100 mL)
2. dry with materialThe combined organic layers were dried over sodium sulfate
3. concentrationconcentrated under reduced pressure