4-bromo-2-chloro-6-iodophenol

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

Procedure: The same procedure as in Example 8 except that 4-bromo-2-iodophenol, 2-bromo-4-chloro-6-iodophenol, 4-bromo-2-chloro-6-iodophenol or 2,4,6-triiodophenol is employed in place of 2,4-dibromo-6-iodophenol yields 3-(4-bromo-2-iodophenoxy)cyclopentene, 3-(2-bromo-4-chloro-6-iodophenoxy)cyclopentene, 3-(4-bromo-2-chloro-6-iodophenoxy)cyclopentene or 3-(2,4,6-triiodophenoxy)cyclopentene, respectively.

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

Procedure: The same procedure as in Example 8 except that 4-bromo-2-iodophenol, 2-bromo-4-chloro-6-iodophenol, 4-bromo-2-chloro-6-iodophenol or 2,4,6-triiodophenol is employed in place of 2,4-dibromo-6-iodophenol yields 3-(4-bromo-2-iodophenoxy)cyclopentene, 3-(2-bromo-4-chloro-6-iodophenoxy)cyclopentene, 3-(4-bromo-2-chloro-6-iodophenoxy)cyclopentene or 3-(2,4,6-triiodophenoxy)cyclopentene, respectively.

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

Procedure: The same procedure as in Example 8 except that 4-bromo-2-iodophenol, 2-bromo-4-chloro-6-iodophenol, 4-bromo-2-chloro-6-iodophenol or 2,4,6-triiodophenol is employed in place of 2,4-dibromo-6-iodophenol yields 3-(4-bromo-2-iodophenoxy)cyclopentene, 3-(2-bromo-4-chloro-6-iodophenoxy)cyclopentene, 3-(4-bromo-2-chloro-6-iodophenoxy)cyclopentene or 3-(2,4,6-triiodophenoxy)cyclopentene, respectively.

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)

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

Procedure: To a solution of 4-bromo-2-chlorophenol (10 g, 48.2 mmol) in 25% aqueous ammonia solution (140 mL) was added a solution of potassium iodide (24 g, 144.6 mmol) and iodine (12.2 g, 48.2 mmol) in water (125 mL). The reaction mixture was stirred at ambient temperature for 4 h and quenched with 100 mL of water. The reaction was acidified by addition of concentrated HCl (150 mL) and extracted with ethyl acetate (3×40 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, 9:1 hexanes/ethyl acetate) providing 4-bromo-2-chloro-6-iodophenol (14 g, 89%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 7.74 (d, J=2.0 Hz, 1H), 7.47 (d, J=2.0 Hz, 1H), 5.93 (s, 1H). quenched with 100 mL of water The reaction was acidified by addition of concentrated HCl (150 mL) extracted with ethyl acetate (3×40 mL) The combined organic extracts were dried over Na2SO4 concentrated in vacuo to give the crude product which was purified by column chromatography (SiO2, 9:1 hexanes/ethyl acetate)

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

Procedure: The same procedure as in Example 8 except that 4-bromo-2-iodophenol, 2-bromo-4-chloro-6-iodophenol, 4-bromo-2-chloro-6-iodophenol or 2,4,6-triiodophenol is employed in place of 2,4-dibromo-6-iodophenol yields 3-(4-bromo-2-iodophenoxy)cyclopentene, 3-(2-bromo-4-chloro-6-iodophenoxy)cyclopentene, 3-(4-bromo-2-chloro-6-iodophenoxy)cyclopentene or 3-(2,4,6-triiodophenoxy)cyclopentene, respectively.