3-ethenyl-2,6-difluorobenzonitrile

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

Procedure: 3-Ethenyl-2,6-difluorobenzonitrile (1.70 g, 10.3 mmol) was added to DCM (10 mL) at 0° C. Then mCPBA (5.33 g, 30.9 mmol) was added and the mixture was stirred at RT for 48 h. The reaction mixture was washed with saturated aqueous Na2S2O3, then with 1N NaOH, and brine. The organic layer was separated and dried over Na2SO4, filtered, and evaporated to dryness. The crude product was purified by MPLC chromatography through a 120 g Redi-sep column, eluting with a 0-100% EtOAc/hexane solvent system. 2,6-Difluoro-3-(oxiran-2-yl)benzonitrile was isolated. The reaction mixture was washed with saturated aqueous Na2S2O3 The organic layer was separated dried over Na2SO4 filtered evaporated to dryness The crude product was purified by MPLC chromatography through a 120 g Redi-sep column eluting with a 0-100% EtOAc/hexane solvent system

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

Procedure: 3-Cyano-2,4-difluorophenyl trifluoromethanesulfonate (5.20 g, 18.1 mmol), potassium vinyl trifluoroborate (4.85 g, 36.2 mmol), PdCl2(dppf)-CH2Cl2 Adduct (0.662 g, 0.905 mmol), and TEA (5.05 mL, 36.2 mmol) were added to 75 mL of ethanol. The reaction mixture was degassed then heated at reflux for 4 h. LC-MS analysis confirmed product peak. The reaction mixture was diluted with ethyl acetate, washed twice with brine, dried, and evaporated to dryness. The crude material was then purified by MPLC chromatography through a 330 g Redi-sep column eluting with 10% EtOAc/Hexane solvent system to yield 3-ethenyl-2,6-difluorobenzonitrile. The reaction mixture was degassed then heated at reflux for 4 h The reaction mixture was diluted with ethyl acetate washed twice with brine dried evaporated to dryness The crude material was then purified by MPLC chromatography through a 330 g Redi-sep column eluting with 10% EtOAc/Hexane solvent system

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

Procedure: 3-Ethenyl-2,6-difluorobenzonitrile (1.70 g, 10.3 mmol) was added to DCM (10 mL) at 0° C. Then mCPBA (5.33 g, 30.9 mmol) was added and the mixture was stirred at RT for 48 h. The reaction mixture was washed with saturated aqueous Na2S2O3, then with 1N NaOH, and brine. The organic layer was separated and dried over Na2SO4, filtered, and evaporated to dryness. The crude product was purified by MPLC chromatography through a 120 g Redi-sep column, eluting with a 0-100% EtOAc/hexane solvent system. 2,6-Difluoro-3-(oxiran-2-yl)benzonitrile was isolated. The reaction mixture was washed with saturated aqueous Na2S2O3 The organic layer was separated dried over Na2SO4 filtered evaporated to dryness The crude product was purified by MPLC chromatography through a 120 g Redi-sep column eluting with a 0-100% EtOAc/hexane solvent system

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

Procedure: 3-Cyano-2,4-difluorophenyl trifluoromethanesulfonate (5.20 g, 18.1 mmol), potassium vinyl trifluoroborate (4.85 g, 36.2 mmol), PdCl2(dppf)-CH2Cl2 Adduct (0.662 g, 0.905 mmol), and TEA (5.05 mL, 36.2 mmol) were added to 75 mL of ethanol. The reaction mixture was degassed then heated at reflux for 4 h. LC-MS analysis confirmed product peak. The reaction mixture was diluted with ethyl acetate, washed twice with brine, dried, and evaporated to dryness. The crude material was then purified by MPLC chromatography through a 330 g Redi-sep column eluting with 10% EtOAc/Hexane solvent system to yield 3-ethenyl-2,6-difluorobenzonitrile. The reaction mixture was degassed then heated at reflux for 4 h The reaction mixture was diluted with ethyl acetate washed twice with brine dried evaporated to dryness The crude material was then purified by MPLC chromatography through a 330 g Redi-sep column eluting with 10% EtOAc/Hexane solvent system