2-(5-bromo-7-chloro-1-benzofuran-2-yl)ethanol

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

Procedure: To a solution of the product of step B (3.5 g, 12.7 mmol) in dichloromethane (30 mL) was added triethylamine (3.7 mL, 25.4 mmol) followed by p-toluenesulfonyl chloride (3.6 mL, 19.05 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 12 h and concentrated in vacuo. The reaction mixture was quenched with saturated sodium bicarbonate solution, washed with 0.5 N HCl and extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the crude product which was purified by column chromatography (SiO2, 4:1 hexanes/ethyl acetate) providing 2-(5-bromo-7-chlorobenzofuran-2-yl)ethyl 4-methylbenzenesulfonate (5.1 g, 95%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 7.66-7.62 (m, 2H), 7.49 (d, J=2.0 Hz, 1H), 7.36 (d, J=1.6 Hz, 1H), 7.18-7.14 (m, 2H), 6.43 (s, 1H), 4.39 (t, J=6.4 Hz, 2H), 3.14 (t, J=6.0 Hz, 2H), 2.37 (s, 3H). concentrated in vacuo The reaction mixture was quenched with saturated sodium bicarbonate solution washed with 0.5 N HCl extracted with ethyl acetate (2×20 mL) The combined organic extracts were dried over Na2SO4 concentrated in vacuo to give the crude product which was purified by column chromatography (SiO2, 4:1 hexanes/ethyl acetate)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The product of step A (14.0 g, 42.76 mmol) was added to a mixture of but-3-yn-1-ol (3.24 mL, 42.79 mmol), copper(II)oxide (3.67 g, 25.67 mmol), pyridine (21.3 mL) and N-methylpyrrolidone (85.0 mL). The reaction mixture was heated to 70° C. for 12 h then 100° C. for a further 2.5 h. The mixture was diluted with MTBE (200 mL), washed successively with 5% aq NH4OH (200 mL), 0.5 M NaOH (200 mL) and saturated brine solution (200 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to give the crude product which was purified by column chromatography (SiO2, 4:1 hexanes/ethyl acetate) providing 2-(5-bromo-7-chlorobenzofuran-2-yl)ethanol (7.8 g, 66%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 7.52 (d, J=1.6 Hz, 1H), 7.37 (d, J=2.0 Hz, 1H), 6.52-6.51 (m, 1H), 4.02 (q, J=6.0 Hz, 2H), 3.09 (t, J=6.2 Hz, 2H), 1.65 (t, J=5.6 Hz, 1H). washed successively with 5% aq NH4OH (200 mL), 0.5 M NaOH (200 mL) and saturated brine solution (200 mL) extracted with ethyl acetate (3×75 mL) The combined organic extracts were dried over Na2SO4 concentrated in vacuo to give the crude product which was purified by column chromatography (SiO2, 4:1 hexanes/ethyl acetate)