2-bromo-4-fluoro-1-(2-methoxyethoxy)benzene

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: To a solution of 2-bromo-4-fluorophenol (1.2 g, 6.28 mmol) in acetonitrile (10 ml) was added potassium carbonate (2.78 g, 20 mmol) and 2-bromoethyl methyl ether (0.85 ml, 9.5 mmol). The resultant solution was heated to reflux for 16 hours. The reaction mixture was cooled then concentrated in vacuo. tert-Butyl-dimethyl ether (20 ml) and sodium hydroxide (1M aqueous solution) (10 ml) were added and the layers were separated. The organic layer was washed with saturated brine solution (10 ml) then dried over anhydrous Na2SO4 (s), filtered and evaporated in vacuo. Purification by column chromatography on silica gel eluting with heptane to heptane:ethyl acetate (9:1) afforded the title compound as a colourless oil (1.03 g, 66%). to reflux for 16 hours The reaction mixture was cooled then concentrated in vacuo tert-Butyl-dimethyl ether (20 ml) and sodium hydroxide (1M aqueous solution) (10 ml) were added the layers were separated The organic layer was washed with saturated brine solution (10 ml) then dried over anhydrous Na2SO4 (s) filtered evaporated in vacuo Purification by column chromatography on silica gel eluting with heptane to heptane:ethyl acetate (9:1)

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

Procedure: To a solution of 2-bromo-4-fluorophenol (1.2 g, 6.28 mmol) in acetonitrile (10 ml) was added potassium carbonate (2.78 g, 20 mmol) and 2-bromoethyl methyl ether (0.85 ml, 9.5 mmol). The resultant solution was heated to reflux for 16 hours. The reaction mixture was cooled then concentrated in vacuo. tert-Butyl-dimethyl ether (20 ml) and sodium hydroxide (1M aqueous solution) (10 ml) were added and the layers were separated. The organic layer was washed with saturated brine solution (10 ml) then dried over anhydrous Na2SO4 (s), filtered and evaporated in vacuo. Purification by column chromatography on silica gel eluting with heptane to heptane:ethyl acetate (9:1) afforded the title compound as a colourless oil (1.03 g, 66%). to reflux for 16 hours The reaction mixture was cooled then concentrated in vacuo tert-Butyl-dimethyl ether (20 ml) and sodium hydroxide (1M aqueous solution) (10 ml) were added the layers were separated The organic layer was washed with saturated brine solution (10 ml) then dried over anhydrous Na2SO4 (s) filtered evaporated in vacuo Purification by column chromatography on silica gel eluting with heptane to heptane:ethyl acetate (9:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-bromo-2-methoxyethane (5.49 g, 39.5 mmol) was added to a mixture of 2-bromo-4-fluoro phenol (5 g, 26.18 mmol) and K2CO3 (11.5 g, 83.25 mmol) in CH3CN (41.5 mL) and continued stirring at 80° C. for 16 hr. The reaction mixture was quenched with 1M aq.NaOH solution, extracted with diethyl ether (3×100 mL), dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude, which was purified by column chromatography (using silica gel and 2% ethyl acetate in hexane as eluent) to afford the desired compound (Int-42). 1H NMR (300 MHz, CDCl3) δ ppm 7.3 (1H, m), 6.9 (1H, m), 6.7 (1H, m), 4.1 (2H, t), 3.8 (2H, t), 3.5 (3H, s). The reaction mixture was quenched with 1M aq NaOH solution, extracted with diethyl ether (3×100 mL) dried over anhydrous sodium sulphate concentrated under reduced pressure to afford the crude, which was purified by column chromatography (using silica gel and 2% ethyl acetate in hexane as eluent)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-bromo-2-methoxyethane (5.49 g, 39.5 mmol) was added to a mixture of 2-bromo-4-fluoro phenol (5 g, 26.18 mmol) and K2CO3 (11.5 g, 83.25 mmol) in CH3CN (41.5 mL) and continued stirring at 80° C. for 16 hr. The reaction mixture was quenched with 1M aq.NaOH solution, extracted with diethyl ether (3×100 mL), dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude, which was purified by column chromatography (using silica gel and 2% ethyl acetate in hexane as eluent) to afford the desired compound (Int-42). 1H NMR (300 MHz, CDCl3) δ ppm 7.3 (1H, m), 6.9 (1H, m), 6.7 (1H, m), 4.1 (2H, t), 3.8 (2H, t), 3.5 (3H, s). The reaction mixture was quenched with 1M aq NaOH solution, extracted with diethyl ether (3×100 mL) dried over anhydrous sodium sulphate concentrated under reduced pressure to afford the crude, which was purified by column chromatography (using silica gel and 2% ethyl acetate in hexane as eluent)

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

Procedure: To a solution of 2-bromo-4-fluorophenol (1.2 g, 6.28 mmol) in acetonitrile (10 ml) was added potassium carbonate (2.78 g, 20 mmol) and 2-bromoethyl methyl ether (0.85 ml, 9.5 mmol). The resultant solution was heated to reflux for 16 hours. The reaction mixture was cooled then concentrated in vacuo. tert-Butyl-dimethyl ether (20 ml) and sodium hydroxide (1M aqueous solution) (10 ml) were added and the layers were separated. The organic layer was washed with saturated brine solution (10 ml) then dried over anhydrous Na2SO4 (s), filtered and evaporated in vacuo. Purification by column chromatography on silica gel eluting with heptane to heptane:ethyl acetate (9:1) afforded the title compound as a colourless oil (1.03 g, 66%). to reflux for 16 hours The reaction mixture was cooled then concentrated in vacuo tert-Butyl-dimethyl ether (20 ml) and sodium hydroxide (1M aqueous solution) (10 ml) were added the layers were separated The organic layer was washed with saturated brine solution (10 ml) then dried over anhydrous Na2SO4 (s) filtered evaporated in vacuo Purification by column chromatography on silica gel eluting with heptane to heptane:ethyl acetate (9:1)