2-(4-bromo-2-fluorophenoxy)acetonitrile

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

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

Procedure: Bromoacetonitrile (1.81 ml, 0.026M) was added to a solution of 4-bromo-2-fluorophenol (5.0 g, 0.026M) and potassium carbonate (3.54 g, 0.026M) in DMF (50 ml). The reaction was stirred for 12 hours and then partitioned between diethyl ether (200 ml) and water (200 ml). The organics were separated, dried over magnesium sulfate, filtered and concentrated in vacuuo to afford the title compound as a yellow oil (6.0 g). 1H NMR (CDCl3): δ 4.84 (s, 2H), 7.03–7.10 (m, 2H), 7.21 (m, 1H). partitioned between diethyl ether (200 ml) and water (200 ml) The organics were separated dried over magnesium sulfate filtered concentrated in vacuuo

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (4-bromo-2-fluorophenoxy)acetonitrile (2.5 g, 10.8 mmol), 1-Cyclopentyl-2-propen-1-ol (2.0 g, 16.2 mmol), dichlorobis (triphenylphosphine) palladium (II) (151 mg, 0.22 mmol), and sodium bicarbonate (1.08 g, 12.9 mmol) in N-methylpyrrolidinone (20 mL) was heated to 140° C. under N2 for 5 hours. The reaction mixture was partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a black oil. The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes) to give the desired product (2.7 g, 93%). 1H NMR (CDCl3): δ 1.52–1.83 (m, 8H), 2.75 (m, 2H), 2.85 (m, 3H), 4.80 (s, 2H), 6.92–7.06 (m, 3H). The reaction mixture was partitioned between 1N HCl and EtOAc The organic layer was washed with saturated NaHCO3, brine dried over Na2SO4 concentrated to a black oil The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes)

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (4-bromo-2-fluorophenoxy)acetonitrile (2.5 g, 10.8 mmol), 1-Cyclopentyl-2-propen-1-ol (2.0 g, 16.2 mmol), dichlorobis (triphenylphosphine) palladium (II) (151 mg, 0.22 mmol), and sodium bicarbonate (1.08 g, 12.9 mmol) in N-methylpyrrolidinone (20 mL) was heated to 140° C. under N2 for 5 hours. The reaction mixture was partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a black oil. The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes) to give the desired product (2.7 g, 93%). 1H NMR (CDCl3): δ 1.52–1.83 (m, 8H), 2.75 (m, 2H), 2.85 (m, 3H), 4.80 (s, 2H), 6.92–7.06 (m, 3H). The reaction mixture was partitioned between 1N HCl and EtOAc The organic layer was washed with saturated NaHCO3, brine dried over Na2SO4 concentrated to a black oil The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes)

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

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

Procedure: Bromoacetonitrile (1.81 ml, 0.026M) was added to a solution of 4-bromo-2-fluorophenol (5.0 g, 0.026M) and potassium carbonate (3.54 g, 0.026M) in DMF (50 ml). The reaction was stirred for 12 hours and then partitioned between diethyl ether (200 ml) and water (200 ml). The organics were separated, dried over magnesium sulfate, filtered and concentrated in vacuuo to afford the title compound as a yellow oil (6.0 g). 1H NMR (CDCl3): δ 4.84 (s, 2H), 7.03-7.10 (m, 2H), 7.21 (m, 1H). partitioned between diethyl ether (200 ml) and water (200 ml) The organics were separated dried over magnesium sulfate filtered concentrated in vacuuo

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (4-bromo-2-fluorophenoxy)acetonitrile (2.5 g, 10.8 mmol), 1-Cyclopentyl-2-propen-1-ol (2.0 g, 16.2 mmol), dichlorobis(triphenylphosphine)palladium (II) (151 mg, 0.22 mmol), and sodium bicarbonate (1.08 g, 12.9 mmol) in N-methylpyrrolidinone (20 mL) was heated to 140° C. under N2 for 5 hours. The reaction mixture was partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a black oil. The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes) to give the desired product (2.7 g, 93%). 1H NMR (CDCl3): δ 1.52-1.83 (m, 8H), 2.75 (m, 2H), 2.85 (m, 3H), 4.80 (s, 2H), 6.92-7.06 (m, 3H). The reaction mixture was partitioned between 1N HCl and EtOAc The organic layer was washed with saturated NaHCO3, brine dried over Na2SO4 concentrated to a black oil The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes)

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

Procedure: Bromoacetonitrile (1.81 ml, 0.026M) was added to a solution of 4-bromo-2-fluorophenol (5.0 g, 0.026M) and potassium carbonate (3.54 g, 0.026M) in DMF (50 ml). The reaction was stirred for 12 hours and then partitioned between diethyl ether (200 ml) and water (200 ml). The organics were separated, dried over magnesium sulfate, filtered and concentrated in vacuuo to afford the title compound as a yellow oil (6.0 g). 1H NMR (CDCl3): δ 4.84 (s, 2H), 7.03–7.10 (m, 2H), 7.21 (m, 1H). partitioned between diethyl ether (200 ml) and water (200 ml) The organics were separated dried over magnesium sulfate filtered concentrated in vacuuo

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (4-bromo-2-fluorophenoxy)acetonitrile (2.5 g, 10.8 mmol), 1-Cyclopentyl-2-propen-1-ol (2.0 g, 16.2 mmol), dichlorobis (triphenylphosphine) palladium (II) (151 mg, 0.22 mmol), and sodium bicarbonate (1.08 g, 12.9 mmol) in N-methylpyrrolidinone (20 mL) was heated to 140° C. under N2 for 5 hours. The reaction mixture was partitioned between 1N HCl and EtOAc. The organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4 and concentrated to a black oil. The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes) to give the desired product (2.7 g, 93%). 1H NMR (CDCl3): δ 1.52–1.83 (m, 8H), 2.75 (m, 2H), 2.85 (m, 3H), 4.80 (s, 2H), 6.92–7.06 (m, 3H). The reaction mixture was partitioned between 1N HCl and EtOAc The organic layer was washed with saturated NaHCO3, brine dried over Na2SO4 concentrated to a black oil The oil was purified by flash column chromatography (Hexanes to 10% EtOAc in hexanes)