3-bromo-2-chloro-6-fluorobenzonitrile

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

Procedure: 3-Bromo-2-chloro-6-fluorobenzonitrile (15.4 g, 65.6 mmol), potassium vinyl trifluoroborate (17.6 g, 131 mmol), triethylamine (18.3 mL, 131 mmol) and PdCl2(dppf)-CH2Cl2 adduct (2.68 g, 3.28 mmol) were added to ethanol (75 mL) then degassed and heated at reflux for 3 h. The reaction was diluted with ethyl acetate and washed with brine, dried and evaporated to dryness. The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10% ethyl acetate/hexane solvent system to yield 2-chloro-6-fluoro-3-vinylbenzonitrile. then degassed heated at reflux for 3 h The reaction was diluted with ethyl acetate washed with brine dried evaporated to dryness The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10% ethyl acetate/hexane solvent system

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

Procedure: 2-Chloro-6-fluorobenzonitrile (15.6 g, 100 mmol) was dissolved in trific acid (75 mL) at 0° C., then NBS (17.8 g, 100 mmol) was added. The reaction was warmed up to room temperature and stirred overnight. The reaction mixture was poured into ice and extracted with DCM (2×). DCM layers were washed with NaHCO3 and brine. The DCM was dried over Na2SO4 then filtered and concentrated. The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10-20% ethyl acetate/hexane solvent system to yield 3-bromo-2-chloro-6-fluorobenzonitrile. The reaction mixture was poured into ice extracted with DCM (2×) DCM layers were washed with NaHCO3 and brine The DCM was dried over Na2SO4 then filtered concentrated The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10-20% ethyl acetate/hexane solvent system

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

Procedure: To a solution of 3-bromo-2-chloro-6-fluorobenzamide (3.56 mmol) in 50 mL DCM were added 1.5 mL Et3N followed by trifluoromethanesulfonic acid anhydride (7.11 mmol) at 0° C. The ice bath was removed and the reaction mixture was stirred at RT. After 30 min, water was added and the mixture was extracted with DCM (3×). The combined organic layers were dried over MgSO4 and concentrated in vacuo to obtain the desired compound as brown solid. The ice bath was removed water was added the mixture was extracted with DCM (3×) The combined organic layers were dried over MgSO4 concentrated in vacuo

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

Procedure: 3-Bromo-2-chloro-6-fluorobenzonitrile (15.4 g, 65.6 mmol), potassium vinyl trifluoroborate (17.6 g, 131 mmol), triethylamine (18.3 mL, 131 mmol) and PdCl2(dppf)-CH2Cl2 adduct (2.68 g, 3.28 mmol) were added to ethanol (75 mL) then degassed and heated at reflux for 3 h. The reaction was diluted with ethyl acetate and washed with brine, dried and evaporated to dryness. The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10% ethyl acetate/hexane solvent system to yield 2-chloro-6-fluoro-3-vinylbenzonitrile. then degassed heated at reflux for 3 h The reaction was diluted with ethyl acetate washed with brine dried evaporated to dryness The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10% ethyl acetate/hexane solvent system

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

Procedure: 2-Chloro-6-fluorobenzonitrile (15.6 g, 100 mmol) was dissolved in triflic acid (75 mL) at 0° C., then NBS (17.8 g, 100 mmol) was added. The reaction was warmed up to room temperature and stirred overnight. The reaction mixture was poured into ice and extracted with DCM (2×). DCM layers were washed with NaHCO3 and brine. The DCM was dried over Na2SO4 then filtered and concentrated. The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10-20% ethyl acetate/hexane solvent system to yield 3-bromo-2-chloro-6-fluorobenzonitrile. The reaction mixture was poured into ice extracted with DCM (2×) DCM layers were washed with NaHCO3 and brine The DCM was dried over Na2SO4 then filtered concentrated The product was purified by chromatography through a 330 g ISCO Redi-Sep column with 10-20% ethyl acetate/hexane solvent system