105942-10-7

133059-44-6

97674-02-7

105942-10-7

a) Preparation of the intermediate: 4-bromo-3-fluorobenzonitrile (6.0 g, 30.00 mmol) and tributyl(1-ethoxyvinyl)tin (11.2 mL, 33.00 mmol) were dissolved in toluene (100 mL) under nitrogen protection and stirred at room temperature. Dichlorobis(triphenylphosphine)palladium(II) (0.72 g, 1.03 mmol) was then added and stirring continued at room temperature. The reaction mixture was heated to reflux temperature and stirred overnight. After the reaction was completed, it was cooled to room temperature and 2 M potassium fluoride solution (50 mL) was slowly added and stirred for 30 minutes. Next, 6 M hydrochloric acid solution (100 mL) was added, heated to 70°C and stirred for 2 hours. The insoluble material was removed by filtration and the filtrate was extracted with ethyl acetate (3 × 80 mL). The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and the solvent was concentrated under reduced pressure. Intermediate 14 was obtained in a yield of 4.3 g, 88% yield.