methyl 2-(4-iodophenoxy)acetate

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

Procedure: A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.075 g, 0.21 mmol) and 4-iodophenoxyacetic acid methyl ester (0.060 g, 0.21 mmol, prepared as described in Example 35a) in dry triethylamine (2 mL) was treated at 80° C. for 1.5 hr by the procedure of Example 11 with a mixture of tetrakis(triphenylphosphine)palladium (0.018 g, 0.016 mmol), cuprous iodide (0.004 g, 0.021 mmol), and triphenylphosphine (crystal). The crude product was chromatographed (silica 40 to 50% ethyl acetate in hexanes) and stripped in vacuo to afford the tided intermediate as a dark red oil (0.080 g, 73%). 1H-NMR (400 MHz, CDCl3) δ 7.98 (d, 9.4 Hz, 2H), 7.50 (d, J=9.4 Hz, 2H), 7.20 (d, J=1.9 Hz, 1H), 7.12 (d-d, J=1.9 Hz, J=8.6 Hz, 1H), 6.84 (d, J=8.6, 1H), 4.80 (p, J=3.8 Hz, 1H), 4.00 (s, br, 4H), 3.92 (s, 3H), 3.85 (s, 3H), 2.3 to 1.5 (m, 17H with H2O). The crude product was chromatographed (silica 40 to 50% ethyl acetate in hexanes)

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

Procedure: A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.150 g, 0.42 mmol) and 4-iodophenoxyacetic acid methyl ester (0.123 g, 0.42 mmol) in dry piperidine (2 mL) was treated at 80° C. for 1.5 hr by the procedure of Example 11 with a mixture of tetrakis(triphenylphosphine)palladium (0.027 g, 0.023 mmol), cuprous iodide (0.0048 g, 0.025 mmol), and triphenylphosphine (crystal). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether) and was stripped in vacuo to afford the titled intermediate as a viscous yellow oil (0.232 g, 96%). 1H-NMR (400 MHz, CDCl3) δ 7.38 (d, J=8.7 Hz, 2H), 7.24 (d, J=2.3 Hz, 1H), 7.13 (d-d, J=8.4 Hz, J=2.3 Hz, 1H), 6.89 (d, J=8.9, 1H), 6.84 (d, J=8.4, 1H),4.81 (p, 1H), 4.69 (s, 2H), 4.00 (s, 4H), 3.84 (s, 3H), 3.56 (t, J=5.5 Hz, 2H), 3.49 (t, J=5.5 Hz, 2H), 2.3 to 1.5 (m, 32H with H2O). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether)

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

Procedure: A stirred mixture of 4-iodophenol (0.50 g, 2.27 mmol), methyl 2-bromoacetate (0.382 g, 2.50 mmol), and powdered potassium carbonate (0.314 g, 2.27 mmol) in dry acetone under argon was sealed and heated at 70° C. for 4 hr. The cooled mixture was filtered, and the filtrate was evaporated in vacuo. The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) and the solvent was removed in vacuo to afford the titled intermediate as a white solid (0.41 g, 62%), mp 69°-70° C. was sealed The cooled mixture was filtered the filtrate was evaporated in vacuo The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) the solvent was removed in vacuo

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

Procedure: A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.075 g, 0.21 mmol) and 4-iodophenoxyacetic acid methyl ester (0.060 g, 0.21 mmol, prepared as described in Example 35a) in dry triethylamine (2 mL) was treated at 80° C. for 1.5 hr by the procedure of Example 11 with a mixture of tetrakis(triphenylphosphine)palladium (0.018 g, 0.016 mmol), cuprous iodide (0.004 g, 0.021 mmol), and triphenylphosphine (crystal). The crude product was chromatographed (silica 40 to 50% ethyl acetate in hexanes) and stripped in vacuo to afford the tided intermediate as a dark red oil (0.080 g, 73%). 1H-NMR (400 MHz, CDCl3) δ 7.98 (d, 9.4 Hz, 2H), 7.50 (d, J=9.4 Hz, 2H), 7.20 (d, J=1.9 Hz, 1H), 7.12 (d-d, J=1.9 Hz, J=8.6 Hz, 1H), 6.84 (d, J=8.6, 1H), 4.80 (p, J=3.8 Hz, 1H), 4.00 (s, br, 4H), 3.92 (s, 3H), 3.85 (s, 3H), 2.3 to 1.5 (m, 17H with H2O). The crude product was chromatographed (silica 40 to 50% ethyl acetate in hexanes)

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

Procedure: A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.150 g, 0.42 mmol) and 4-iodophenoxyacetic acid methyl ester (0.123 g, 0.42 mmol) in dry piperidine (2 mL) was treated at 80° C. for 1.5 hr by the procedure of Example 11 with a mixture of tetrakis(triphenylphosphine)palladium (0.027 g, 0.023 mmol), cuprous iodide (0.0048 g, 0.025 mmol), and triphenylphosphine (crystal). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether) and was stripped in vacuo to afford the titled intermediate as a viscous yellow oil (0.232 g, 96%). 1H-NMR (400 MHz, CDCl3) δ 7.38 (d, J=8.7 Hz, 2H), 7.24 (d, J=2.3 Hz, 1H), 7.13 (d-d, J=8.4 Hz, J=2.3 Hz, 1H), 6.89 (d, J=8.9, 1H), 6.84 (d, J=8.4, 1H),4.81 (p, 1H), 4.69 (s, 2H), 4.00 (s, 4H), 3.84 (s, 3H), 3.56 (t, J=5.5 Hz, 2H), 3.49 (t, J=5.5 Hz, 2H), 2.3 to 1.5 (m, 32H with H2O). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether)

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

Procedure: A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.150 g, 0.42 mmol) and 4-iodophenoxyacetic acid methyl ester (0.123 g, 0.42 mmol) in dry piperidine (2 mL) was treated at 80° C. for 1.5 hr by the procedure of Example 11 with a mixture of tetrakis(triphenylphosphine)palladium (0.027 g, 0.023 mmol), cuprous iodide (0.0048 g, 0.025 mmol), and triphenylphosphine (crystal). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether) and was stripped in vacuo to afford the titled intermediate as a viscous yellow oil (0.232 g, 96%). 1H-NMR (400 MHz, CDCl3) δ 7.38 (d, J=8.7 Hz, 2H), 7.24 (d, J=2.3 Hz, 1H), 7.13 (d-d, J=8.4 Hz, J=2.3 Hz, 1H), 6.89 (d, J=8.9, 1H), 6.84 (d, J=8.4, 1H),4.81 (p, 1H), 4.69 (s, 2H), 4.00 (s, 4H), 3.84 (s, 3H), 3.56 (t, J=5.5 Hz, 2H), 3.49 (t, J=5.5 Hz, 2H), 2.3 to 1.5 (m, 32H with H2O). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether)

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

Procedure: A stirred mixture of 4-iodophenol (0.50 g, 2.27 mmol), methyl 2-bromoacetate (0.382 g, 2.50 mmol), and powdered potassium carbonate (0.314 g, 2.27 mmol) in dry acetone under argon was sealed and heated at 70° C. for 4 hr. The cooled mixture was filtered, and the filtrate was evaporated in vacuo. The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) and the solvent was removed in vacuo to afford the titled intermediate as a white solid (0.41 g, 62%), mp 69°-70° C. was sealed The cooled mixture was filtered the filtrate was evaporated in vacuo The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) the solvent was removed in vacuo

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

Procedure: A stirred mixture of 4-iodophenol (0.50 g, 2.27 mmol), methyl 2-bromoacetate (0.382 g, 2.50 mmol), and powdered potassium carbonate (0.314 g, 2.27 mmol) in dry acetone under argon was sealed and heated at 70° C. for 4 hr. The cooled mixture was filtered, and the filtrate was evaporated in vacuo. The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) and the solvent was removed in vacuo to afford the titled intermediate as a white solid (0.41 g, 62%), mp 69°-70° C. was sealed The cooled mixture was filtered the filtrate was evaporated in vacuo The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) the solvent was removed in vacuo

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

Procedure: A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.075 g, 0.21 mmol) and 4-iodophenoxyacetic acid methyl ester (0.060 g, 0.21 mmol, prepared as described in Example 35a) in dry triethylamine (2 mL) was treated at 80° C. for 1.5 hr by the procedure of Example 11 with a mixture of tetrakis(triphenylphosphine)palladium (0.018 g, 0.016 mmol), cuprous iodide (0.004 g, 0.021 mmol), and triphenylphosphine (crystal). The crude product was chromatographed (silica 40 to 50% ethyl acetate in hexanes) and stripped in vacuo to afford the tided intermediate as a dark red oil (0.080 g, 73%). 1H-NMR (400 MHz, CDCl3) δ 7.98 (d, 9.4 Hz, 2H), 7.50 (d, J=9.4 Hz, 2H), 7.20 (d, J=1.9 Hz, 1H), 7.12 (d-d, J=1.9 Hz, J=8.6 Hz, 1H), 6.84 (d, J=8.6, 1H), 4.80 (p, J=3.8 Hz, 1H), 4.00 (s, br, 4H), 3.92 (s, 3H), 3.85 (s, 3H), 2.3 to 1.5 (m, 17H with H2O). The crude product was chromatographed (silica 40 to 50% ethyl acetate in hexanes)

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

Procedure: A stirred mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.150 g, 0.42 mmol) and 4-iodophenoxyacetic acid methyl ester (0.123 g, 0.42 mmol) in dry piperidine (2 mL) was treated at 80° C. for 1.5 hr by the procedure of Example 11 with a mixture of tetrakis(triphenylphosphine)palladium (0.027 g, 0.023 mmol), cuprous iodide (0.0048 g, 0.025 mmol), and triphenylphosphine (crystal). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether) and was stripped in vacuo to afford the titled intermediate as a viscous yellow oil (0.232 g, 96%). 1H-NMR (400 MHz, CDCl3) δ 7.38 (d, J=8.7 Hz, 2H), 7.24 (d, J=2.3 Hz, 1H), 7.13 (d-d, J=8.4 Hz, J=2.3 Hz, 1H), 6.89 (d, J=8.9, 1H), 6.84 (d, J=8.4, 1H),4.81 (p, 1H), 4.69 (s, 2H), 4.00 (s, 4H), 3.84 (s, 3H), 3.56 (t, J=5.5 Hz, 2H), 3.49 (t, J=5.5 Hz, 2H), 2.3 to 1.5 (m, 32H with H2O). The crude product was chromatographed (silica 50 to 75% ethyl acetate in petroleum ether)

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

Procedure: A stirred mixture of 4-iodophenol (0.50 g, 2.27 mmol), methyl 2-bromoacetate (0.382 g, 2.50 mmol), and powdered potassium carbonate (0.314 g, 2.27 mmol) in dry acetone under argon was sealed and heated at 70° C. for 4 hr. The cooled mixture was filtered, and the filtrate was evaporated in vacuo. The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) and the solvent was removed in vacuo to afford the titled intermediate as a white solid (0.41 g, 62%), mp 69°-70° C. was sealed The cooled mixture was filtered the filtrate was evaporated in vacuo The residue was purified by chromatography (silica, 40 to 50% methylene chloride in cyclohexane) the solvent was removed in vacuo