5-bromo-4-fluoro-2-methoxybenzonitrile

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 mL flask was added 5-bromo-4-fluoro-2-methoxybenzonitrile (4.00 g, 17.4 mmol), Bis(Triphenylphosphine)Palladium(II)Chloride (0.61 g, 0.87 mmol), tributyl(1-ethoxy-vinyl)tin (9.42 mL, 26.1 mmol) followed by addition of 1,4 dioxane (40 mL). The resulting mixture was stirred at 95° C. for 3 h; the flask was taken out of the oil bath and cooled to rt followed by treatment with a mixture of THF/H2O (50/25 mL) and placed in an ice bath. To the flask was added NBS (6.19 g, 34.8 mmol) in small portions; after stirred for 0.5 h at 0° C., LC indicated formation of the desired product. The reaction mixture was taken out of the ice bath and slowly warmed up to rt. The reaction mixture was extracted with EtOAc (3×100 mL), washed with brine and water, it was then dried (Na2SO4), filtered and concentrated to dryness followed by separation over silica gel with the solvent systems of hexanes/EtOAc (1/0.5) to give the desired product. LC/MS: [(M+2)]+=274. cooled to rt placed in an ice bath after stirred for 0.5 h at 0° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-fluoro-2-methoxybenzonitrile (35 g, 0.23 mol) in 300 mL of concentrated H2SO4 was added NBS (42 g, 0.23 mol) portionwise at −10° C. and the reaction was stirred at r.t. for 2 hours. Then the reaction was poured into 2 L of ice portionwise, and the solid precipitated out was filtered. The filter cake was washed with water, then the solid was dried in vacuo to give 5-bromo-4-fluoro-2-methoxybenzonitrile. the solid precipitated out was filtered The filter cake was washed with water the solid was dried in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 mL flask was added 4-fluoro-2-methoxybenzonitrile (9.00 g, 59.5 mmol), NBS (12.7 g, 71.5 mmol) and TFA (40 mL); the resulting mixture was stirred for 4 h at 65° C. Analysis of the reaction by LC indicated completion of the reaction. The reaction mixture was concentrated to dryness, treated with EtOAc (200 mL) and washed with brine and water, dried (Na2SO4), filtered and concentrated to dryness. The resulting organic residue was purified by MPLC with the solvent systems of hexanes/EtOAc=1/1 to furnish the desired product: LC/MS: [(M+2)]+=232; Analysis of the reaction by LC completion of the reaction The reaction mixture was concentrated to dryness treated with EtOAc (200 mL) washed with brine and water dried (Na2SO4) filtered concentrated to dryness The resulting organic residue was purified by MPLC with the solvent systems of hexanes/EtOAc=1/1