4-ethenyl-2-fluorobenzonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Into a cooled solution (−78° C.) of 2-fluoro-4-vinylbenzonitrile (1.3 g, 8.8 mmol; see step (i) above) in 40 mL of CH2Cl2 and 5 mL of methanol was to bubbled ozone (50 L/h, 29 g/m3) for 30 min. Argon was subsequently bubbled through to remove excess ozone. Sodium borohydride (0.67 g, 0.018 mol) was added and the cooling bath was removed. The mixture was stirred and allowed to react for 1 h. The mixture was evaporated and 2M HCl was added. The mixture was extracted twice with diethyl ether and the combined ether fraction was dried (Na2SO4) and evaporated. The crude product crystallised. Yield: 1.1 g (81%). to bubbled ozone (50 L/h, 29 g/m3) for 30 min Argon was subsequently bubbled through to remove excess ozone the cooling bath was removed to react for 1 h The mixture was evaporated 2M HCl was added The mixture was extracted twice with diethyl ether the combined ether fraction was dried (Na2SO4) evaporated The crude product crystallised

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

Procedure: A solution of 4-bromo-2-fluorobenzonitrile (4.92 g, 0.0246 mol), vinyltributyltin (0.78 g, 0.246 mol), and tetrakistriphenylphosphine (0.67 g, 0.58 mmol) in 250 mL of toluene was refluxed under nitrogen overnight. The solvent was evaporated and the residue was flash chromatographed on silica gel with heptane:CH2Cl2 (1:1) to pure CH2Cl2. A colourless oil was obtained that crystallised. Yield: 3.0 g (82%). The solvent was evaporated chromatographed on silica gel with heptane:CH2Cl2 (1:1) to pure CH2Cl2 A colourless oil was obtained that crystallised

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

Procedure: Into a cooled solution (−78° C.) of 2-fluoro-4-vinylbenzonitrile (1.3 g, 8.8 mmol; see step (i) above) in 40 mL of CH2Cl2 and 5 mL of methanol was bubbled ozone (50 L/h, 29 g/m3) for 30 min. Argon was subsequently bubbled through to remove excess ozone. Sodium borohydride (0.67 g, 0.018 mol) was added and the cooling bath was removed. The mixture was stirred and allowed to react for 1 h. The mixture was evaporated and 2M HCl was added. The mixture was extracted twice with diethyl ether and the combined ether fraction was dried (Na2SO4) and evaporated. The crude product crystallised. Yield: 1.1 g (81%). Argon was subsequently bubbled through to remove excess ozone the cooling bath was removed to react for 1 h The mixture was evaporated 2M HCl was added The mixture was extracted twice with diethyl ether the combined ether fraction was dried (Na2SO4) evaporated The crude product crystallised

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

Procedure: A solution of 4-bromo-2-fluorobenzonitrile (4.92 g, 0.0246 mol), vinyltributyltin (0.78 g, 0.246 mol), and tetrakistriphenylphosphine (0.67 g, 0.58 mmol) in 250 mL of toluene was refluxed under nitrogen overnight. The solvent was evaporated and the residue was flash chromatographed on silica gel with heptane:CH2Cl2 (1:1) to pure CH2Cl2. A colourless oil was obtained that crystallised. Yield: 3.0 g (82%). The solvent was evaporated chromatographed on silica gel with heptane:CH2Cl2 (1:1) to pure CH2Cl2 A colourless oil was obtained that crystallised

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

Procedure: To a solution of 4-ethenyl-2-fluorobenzonitrile (18.0 g, 122 mmol) in 200 mL of DCM was slowly added mCPBA (74.8 g, 367.347 mmol) in portions at 0° C. The mixture was warmed to room temperature and stirred overnight. The solution was washed with aqueous Na2SO3 until KI paper didn't change color. The organic layers was washed with brine and then concentrated. The residue was purified via column chromatography to give 2-fluoro-4-oxiran-2-ylbenzonitrile: 1H-NMR (400 MHz, CDCl3) δ ppm 7.59˜7.62 (m, 1H), 7.12˜7.22 (m, 2H), 3.89˜3.91 (m, 1H), 3.20˜3.22 (m, 1H), 2.72˜2.74 (m, 1H). at 0° C The solution was washed with aqueous Na2SO3 until KI paper didn't change color The organic layers was washed with brine concentrated The residue was purified via column chromatography

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

Procedure: A solution of 2-(4-cyano-3-fluorophenyl)ethyl methanesulfonate (35.0 g, 144 mmol) and triethylamine (50 mL) in DCM (200 mL) was added DBU (50 mL) dropwise to at 0° C. After stirring at room temperature overnight, the solution was diluted with DCM, washed with 1 N HCl and brine, and dried over anhydrous sodium sulphate and concentrated. The residue was purified by column chromatography to give title compound. washed with 1 N HCl and brine dried over anhydrous sodium sulphate concentrated The residue was purified by column chromatography

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

Procedure: To a solution of 4-ethenyl-2-fluorobenzonitrile (18.0 g, 122 mmol) in 200 mL of DCM was slowly added mCPBA (74.8 g, 367.347 mmol) in portions at 0° C. The mixture was warmed to room temperature and stirred overnight. The solution was washed with aqueous Na2SO3 until KI paper didn't change color. The organic layers was washed with brine and then concentrated. The residue was purified via column chromatography to give 2-fluoro-4-oxiran-2-ylbenzonitrile. at 0° C The solution was washed with aqueous Na2SO3 until KI paper didn't change color The organic layers was washed with brine concentrated The residue was purified via column chromatography

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

Procedure: A solution of 2-(4-cyano-3-fluorophenyl)ethyl methanesulfonate (35.0 g, 144 mmol) and triethylamine (50 mL) in DCM (200 mL) was added DBU (50 mL) dropwise to at 0° C. After stirring at room temperature overnight, the solution was diluted with DCM, washed with 1 N HCl and brine, and dried over anhydrous sodium sulphate and concentrated. The residue was purified by column chromatography to give 4-ethenyl-2-fluorobenzonitrile. 1H-NMR (400 MHz, CDCl3) δ ppm 7.53˜7.57 (m, 1H), 7.20˜7.26 (m, 2H), 6.64˜6.71 (m, 1H), 5.48˜5.90 (m, 2H). washed with 1 N HCl and brine dried over anhydrous sodium sulphate concentrated The residue was purified by column chromatography

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

Procedure: A solution of 4-bromo-2-fluorobenzonitrile (4.92 g, 0.0246 mol), vinyltributyltin (0.78 g, 0.246 mol), and tetrakistriphenylphosphine (0.67 g, 0.58 mmol) in 250 mL of toluene was refluxed under nitrogen overnight. The solvent was evaporated and the residue was flash chromatographed on silica gel with heptane:CH2Cl2 (1:1) to pure CH2Cl2. A colourless oil was obtained that crystallised. Yield: 3.0 g (82%). The solvent was evaporated chromatographed on silica gel with heptane:CH2Cl2 (1:1) to pure CH2Cl2 A colourless oil was obtained that crystallised

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

Procedure: To a solution of 4-ethenyl-2-fluorobenzonitrile (18.0 g, 122 mmol) in 200 mL of DCM was slowly added mCPBA (74.8 g, 367.347 mmol) in portions at 0° C. The mixture was warmed to room temperature and stirred overnight. The solution was washed with aqueous Na2SO3 until KI paper didn't change color. The organic layers was washed with brine and then concentrated. The residue was purified via column chromatography to give 2-fluoro-4-oxiran-2-ylbenzonitrile. 1H-NMR (400 MHz, CDCl3) δ ppm 7.59˜7.62 (m, 1H), 7.12˜7.22 (m, 2H), 3.89˜3.91 (m, 1H), 3.20˜3.22 (m, 1H), 2.72˜2.74 (m, 1H). at 0° C The solution was washed with aqueous Na2SO3 until KI paper didn't change color The organic layers was washed with brine concentrated The residue was purified via column chromatography