2-(4-iodophenoxy)ethanamine

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

Procedure: To a magnetically stirred solution of 4-iodophenol (15 grams, 0.068 mol) in 100 mL THF was sequentially added triphenylphosphine (19.67 grams, 0.075 mol), diethyl azodicarboxylate (13.06 grams, 0.073 mol), and 2-azidoethanol (5.93 grams, 0.068 mol). The mixture was stirred overnight, concentrated in vacuo, diluted with 90 mL ethyl acetate and diluted with hexane (400 mL), and the resulting solids filtered away. The filtrate was concentrated in vacuo, diluted with diethyl ether, and extracted with 1N NaOH and water. Pentane was added to induce precipitation of a white solid that was again filtered away. The filtrate was concentrated in vacuo, and dissolved in methanol (60 mL). Triethylamine (27 grams, 0.267 mol) and propanedithiol (23 grams, 0.215 mol) were added and the mixture stirred at room temperature overnight. The solution was diluted with 100 mL water and partitioned between methylene chloride and 1N NaOH. The organic layer was extracted with 2×200 mL 1N HCl and the aqueous layer washed with 100 mL methylene chloride, made basic with 2N NaOH and extracted 3×75 mL methylene chloride. The combined organics were dried over sodium carbonate, filtered and concentrated in vacuo to yield 12.97 grams of 2-(4-iodophenoxy)ethyl amine (72%). 1NMR (CDCl3, dTMS) 7.56 (2H, d, 3JHH =9 Hz, Ar-H), 6.63 (2H, d, 3JHH =9 Hz, Ar-H), 4.03 (2H, t, 3JHH =5 Hz, CH2N3), 3.57 (2H, t, 3JHH =5 Hz, OCH2). 13C NMR (CDCl3) 158.0, 138.2, 116.9, 83.4, 66.9, 49.9. IR (NaCl, cm-1) 2930, 2107 (s), 1589, 1483, 1284, 1237, 1058, 819. concentrated in vacuo diluted with 90 mL ethyl acetate diluted with hexane (400 mL) the resulting solids filtered away The filtrate was concentrated in vacuo diluted with diethyl ether extracted with 1N NaOH and water Pentane was added precipitation of a white solid that was again filtered away The filtrate was concentrated in vacuo dissolved in methanol (60 mL) the mixture stirred at room temperature overnight partitioned between methylene chloride and 1N NaOH The organic layer was extracted with 2×200 mL 1N HCl the aqueous layer washed with 100 mL methylene chloride extracted 3×75 mL methylene chloride The combined organics were dried over sodium carbonate filtered concentrated in vacuo

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

Procedure: To a magnetically stirred solution of 4-iodophenol (15 grams, 0.068 mol) in 100 mL THF was sequentially added triphenylphosphine (19.67 grams, 0.075 mol), diethyl azodicarboxylate (13.06 grams, 0.073 mol), and 2-azidoethanol (5.93 grams, 0.068 mol). The mixture was stirred overnight, concentrated in vacuo, diluted with 90 mL ethyl acetate and diluted with hexane (400 mL), and the resulting solids filtered away. The filtrate was concentrated in vacuo, diluted with diethyl ether, and extracted with 1N NaOH and water. Pentane was added to induce precipitation of a white solid that was again filtered away. The filtrate was concentrated in vacuo, and dissolved in methanol (60 mL). Triethylamine (27 grams, 0.267 mol) and propanedithiol (23 grams, 0.215 mol) were added and the mixture stirred at room temperature overnight. The solution was diluted with 100 mL water and partitioned between methylene chloride and 1N NaOH. The organic layer was extracted with 2×200 mL 1N HCl and the aqueous layer washed with 100 mL methylene chloride, made basic with 2N NaOH and extracted 3×75 mL methylene chloride. The combined organics were dried over sodium carbonate, filtered and concentrated in vacuo to yield 12.97 grams of 2-(4-iodophenoxy)ethyl amine (72%). 1NMR (CDCl3, dTMS) 7.56 (2H, d, 3JHH =9 Hz, Ar-H), 6.63 (2H, d, 3JHH =9 Hz, Ar-H), 4.03 (2H, t, 3JHH =5 Hz, CH2N3), 3.57 (2H, t, 3JHH =5 Hz, OCH2). 13C NMR (CDCl3) 158.0, 138.2, 116.9, 83.4, 66.9, 49.9. IR (NaCl, cm-1) 2930, 2107 (s), 1589, 1483, 1284, 1237, 1058, 819. concentrated in vacuo diluted with 90 mL ethyl acetate diluted with hexane (400 mL) the resulting solids filtered away The filtrate was concentrated in vacuo diluted with diethyl ether extracted with 1N NaOH and water Pentane was added precipitation of a white solid that was again filtered away The filtrate was concentrated in vacuo dissolved in methanol (60 mL) the mixture stirred at room temperature overnight partitioned between methylene chloride and 1N NaOH The organic layer was extracted with 2×200 mL 1N HCl the aqueous layer washed with 100 mL methylene chloride extracted 3×75 mL methylene chloride The combined organics were dried over sodium carbonate filtered concentrated in vacuo

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

Procedure: To a solution of [2-(4-iodophenoxy)ethyl]amine (6.14 g) in dimethyl sulfoxide (50 ml) was added N,O-bis(trimethylsilyl)acetamide (2.88 ml) and the mixture was stirred for 1 hour. To the mixture was added a solution of (2R)-2-(4-nitrophenyl)oxirane (3.21 g) in dimethyl sulfoxide (10 ml) and the mixture was stirred for 37 hours. After cooling to room temperature, the mixture was quenched by the addition of 5% acetic acid/water (120 ml) and stirred for 30 minutes. The mixture was basified with 1N sodium hydroxide and extracted with ethyl acetate (120 ml). The extract was washed with water (120 ml×2) and brine (120 ml), and dried over magnesium sulfate. Filtration followed by evaporation gave (1R)-2-[[2-(4-iodophenoxy)ethyl]amino]-1-(4-nitrophenyl)ethanol (7.52 g) as a brown solid. The compound was used in the next step without further purification. the mixture was stirred for 37 hours the mixture was quenched by the addition of 5% acetic acid/water (120 ml) stirred for 30 minutes extracted with ethyl acetate (120 ml) The extract was washed with water (120 ml×2) and brine (120 ml) dried over magnesium sulfate Filtration followed by evaporation

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

Procedure: To a solution of [2-(4-iodophenoxy)ethyl]amine (6.14 g) in dimethyl sulfoxide (50 ml) was added N,O-bis(trimethylsilyl)acetamide (2.88 ml) and the mixture was stirred for 1 hour. To the mixture was added a solution of (2R)-2-(4-nitrophenyl)oxirane (3.21 g) in dimethyl sulfoxide (10 ml) and the mixture was stirred for 37 hours. After cooling to room temperature, the mixture was quenched by the addition of 5% acetic acid/water (120 ml) and stirred for 30 minutes. The mixture was basified with 1N sodium hydroxide and extracted with ethyl acetate (120 ml). The extract was washed with water (120 ml×2) and brine (120 ml), and dried over magnesium sulfate. Filtration followed by evaporation gave (1R)-2-[[2-(4-iodophenoxy)ethyl]amino]-1-(4-nitrophenyl)ethanol (7.52 g) as a brown solid. The compound was used in the next step without further purification. the mixture was stirred for 37 hours the mixture was quenched by the addition of 5% acetic acid/water (120 ml) stirred for 30 minutes extracted with ethyl acetate (120 ml) The extract was washed with water (120 ml×2) and brine (120 ml) dried over magnesium sulfate Filtration followed by evaporation

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

Procedure: To a solution of [2-(4-iodophenoxy)ethyl]amine (6.14 g) in dimethyl sulfoxide (50 ml) was added N,O-bis(trimethylsilyl)acetamide (2.88 ml) and the mixture was stirred for 1 hour. To the mixture was added a solution of (2R)-2-(4-nitrophenyl)oxirane (3.21 g) in dimethyl sulfoxide (10 ml) and the mixture was stirred for 37 hours. After cooling to room temperature, the mixture was quenched by the addition of 5% acetic acid/water (120 ml) and stirred for 30 minutes. The mixture was basified with 1N sodium hydroxide and extracted with ethyl acetate (120 ml). The extract was washed with water (120 ml×2) and brine (120 ml), and dried over magnesium sulfate. Filtration followed by evaporation gave (1R)-2-[[2-(4-iodophenoxy)ethyl]amino]-1-(4-nitrophenyl)ethanol (7.52 g) as a brown solid. The compound was used in the next step without further purification. the mixture was stirred for 37 hours the mixture was quenched by the addition of 5% acetic acid/water (120 ml) stirred for 30 minutes extracted with ethyl acetate (120 ml) The extract was washed with water (120 ml×2) and brine (120 ml) dried over magnesium sulfate Filtration followed by evaporation

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of [2-(4-iodophenoxy)ethyl]amine hydrochloride (7.0 g) in chloroform (70 ml) was added saturated sodium bicarbonate solution (70 ml) and the mixture was warmed to 50° C. and stirred for 15 minutes. The organic layer was separated and dried over magnesium sulfate. Filtration followed by evaporation gave [2-(4-iodophenoxy)ethyl]amine (6.13 g) as a white solid. The compound was used in the next step without further purification. The organic layer was separated dried over magnesium sulfate Filtration followed by evaporation

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of [2-(4-iodophenoxy)ethyl]amine hydrochloride (7.0 g) in chloroform (70 ml) was added saturated sodium bicarbonate solution (70 ml) and the mixture was warmed to 50° C. and stirred for 15 minutes. The organic layer was separated and dried over magnesium sulfate. Filtration followed by evaporation gave [2-(4-iodophenoxy)ethyl]amine (6.13 g) as a white solid. The compound was used in the next step without further purification. The organic layer was separated dried over magnesium sulfate Filtration followed by evaporation

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

Procedure: To a magnetically stirred solution of 4-iodophenol (15 grams, 0.068 mol) in 100 mL THF was sequentially added triphenylphosphine (19.67 grams, 0.075 mol), diethyl azodicarboxylate (13.06 grams, 0.073 mol), and 2-azidoethanol (5.93 grams, 0.068 mol). The mixture was stirred overnight, concentrated in vacuo, diluted with 90 mL ethyl acetate and diluted with hexane (400 mL), and the resulting solids filtered away. The filtrate was concentrated in vacuo, diluted with diethyl ether, and extracted with 1N NaOH and water. Pentane was added to induce precipatation of a white solid that was again filtered away. The fitrate was concentrated in vacuo, and dissolved in methanol (60 mL). Triethylamine (27 grams, 0.267 mol) and propanedithiol (23 grams, 0.215 mol) were added and the mixture stirred at room temperature overnight. The solution was diluted with 100 mL water and partitioned between methylene chloride and 1N NaOH. The organic layer was extracted with 2×200 mL 1N HCl and the aqueous layer washed with 100 mL methylene chloride, made basic with 2N NaOH and extracted 3×75 mL methylene chloride. The combined organics were dried over sodium carbonate, filtered and concentrated in vacuo to yield 12.97 grams of 2-(4-iodophenoxy)ethyl amine (72%). 1H NMR (CDCl3, dTMS) 7.56 (2H, d, 3JHH =9 Hz, Ar-H), 6.63 (2H, d, 3JHH =9 Hz, Ar-H), 4.03 (2H, t, 3JHH =5 Hz, CH2N3), 3.57 (2H, t, 3JHH =5 Hz, OCH2). 13C NMR (CDCl3) 158.0, 138.2, 116.9, 83.4, 66.9, 49.9. IR (NaCl, cm-1) 2930, 2107 (s), 1589, 1483, 1284, 1237, 1058, 819. concentrated in vacuo diluted with 90 mL ethyl acetate diluted with hexane (400 mL) the resulting solids filtered away The filtrate was concentrated in vacuo diluted with diethyl ether extracted with 1N NaOH and water Pentane was added that was again filtered away The fitrate was concentrated in vacuo dissolved in methanol (60 mL) the mixture stirred at room temperature overnight partitioned between methylene chloride and 1N NaOH The organic layer was extracted with 2×200 mL 1N HCl the aqueous layer washed with 100 mL methylene chloride extracted 3×75 mL methylene chloride The combined organics were dried over sodium carbonate filtered concentrated in vacuo

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

Procedure: To a magnetically stirred solution of 4-iodophenol (15 grams, 0.068 mol) in 100 mL THF was sequentially added triphenylphosphine (19.67 grams, 0.075 mol), diethyl azodicarboxylate (13.06 grams, 0.073 mol), and 2azidoethanol (5.93 grams, 0.068 mol). The mixture was stirred overnight, concentrated in vacuo, diluted with 90 mL ethyl acetate and diluted with hexane (400 mL), and the resulting solids filtered away. The filtrate was concentrated in vacuo, diluted with diethyl ether, and extracted with 1N NaOH and water. Pentane was added to induce precipatation of a white solid that was again filtered away. The fitrate was concentrated in vacuo, and dissolved in methanol (60 mL). Triethylamine (27 grams, 0.267 mol) and propanedithiol (23 grams, 0.215 mol) were added and the mixture stirred at room temperature overnight. The solution was diluted with 100 mL water and partitioned between methylene chloride and 1N NaOH. The organic layer was extracted with 2×200 mL 1N HCl and the aqueous layer washed with 100 mL methylene chloride, made basic with 2N NaOH and extracted 3×75 mL methylene chloride. The combined organics were dried over sodium carbonate, filtered and concentrated in vacuo to yield 12.97 grams of 2-(4-iodophenoxy)ethyl amine (72%). 1H NMR (CDCl3, dTMS) 7.56 (2H, d, 3JHH =9 Hz, Ar--H), 6.63 (2H, d, 3JHH =9 Hz, Ar--H), 4.03 (2H, t, 3JHH =5 Hz, CH2N3), 3.57 (2H, t, 3JHH =5 Hz, OCH2). 13C NMR (CDCl3) 158.0, 138.2, 116.9, 83.4, 66.9, 49.9. IR (NaCl, cm-1) 2930, 2107 (s), 1589, 1483, 1284, 1237, 1058, 819. concentrated in vacuo diluted with 90 mL ethyl acetate diluted with hexane (400 mL) the resulting solids filtered away The filtrate was concentrated in vacuo diluted with diethyl ether extracted with 1N NaOH and water Pentane was added that was again filtered away The fitrate was concentrated in vacuo dissolved in methanol (60 mL) the mixture stirred at room temperature overnight partitioned between methylene chloride and 1N NaOH The organic layer was extracted with 2×200 mL 1N HCl the aqueous layer washed with 100 mL methylene chloride extracted 3×75 mL methylene chloride The combined organics were dried over sodium carbonate filtered concentrated in vacuo

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

Procedure: To a magnetically stirred solution of 4-iodophenol (15 grams, 0.068 mol) in 100 mL THF was sequentially added triphenylphosphine (19.67 grams, 0.075 mol), diethyl azodicarboxylate (13.06 grams, 0.073 mol), and 2-azidoethanol (5.93 grams, 0.068 mol). The mixture was stirred overnight, concentrated in vacuo, diluted with 90 mL ethyl acetate and diluted with hexane (400 mL), and the resulting solids filtered away. The filtrate was concentrated in vacuo, diluted with diethyl ether, and extracted with 1N NaOH and water. Pentane was added to induce precipitation of a white solid that was again filtered away. The filtrate was concentrated in vacuo, and dissolved in methanol (60 mL). Triethylamine (27 grams, 0.267 mol) and propanedithiol (23 grams, 0.215 mol) were added and the mixture stirred at room temperature overnight. The solution was diluted with 100 mL water and partitioned between methylene chloride and 1N NaOH. The organic layer was extracted with 2×200 mL 1N HCl and the aqueous layer washed with 100 L methylene chloride, made basic with 2N NaOH and extracted 3×75 mL methylene chloride. The combined organics were dried over sodium carbonate, filtered and concentrated in vacuo to yield 12.97 grams of 2-(4-iodophenoxy)ethyl amine (72%). 1H NMR (CDCl3, dTMS) 7.56 (2H, d, 3JHH =9 Hz, Ar--H), 6.63 (2H, d, 3JHH =9 Hz, Ar--H), 4.03 (2H, t, 3JHH =5 Hz, CH2N3), 3.57 (2H, t, 3JHH =5 Hz, OCH2). 13C NMR (CDCl3) 158.0, 138.2, 116.9, 83.4, 66.9, 49.9. IR (NaCl, cm-1) 2930,2107 (s), 1589, 1483, 1284, 1237, 1058, 819. concentrated in vacuo diluted with 90 mL ethyl acetate diluted with hexane (400 mL) the resulting solids filtered away The filtrate was concentrated in vacuo diluted with diethyl ether extracted with 1N NaOH and water Pentane was added precipitation of a white solid that was again filtered away The filtrate was concentrated in vacuo dissolved in methanol (60 mL) the mixture stirred at room temperature overnight partitioned between methylene chloride and 1N NaOH The organic layer was extracted with 2×200 mL 1N HCl the aqueous layer washed with 100 L methylene chloride extracted 3×75 mL methylene chloride The combined organics were dried over sodium carbonate filtered concentrated in vacuo

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

Procedure: To a magnetically stirred solution of 4-iodophenol (15 grams, 0.068 mol) in 100 mL THF was sequentially added triphenylphosphine (19.67 grams, 0.075 mol), diethyl azodicarboxylate (13.06 grams, 0.073 mol), and 2-azidoethanol (5.93 grams, 0.068 mol). The mixture was stirred overnight, concentrated in vacuo, diluted with 90 mL ethyl acetate and diluted with hexane (400 mL), and the resulting solids filtered away. The filtrate was concentrated in vacuo, diluted with diethyl ether, and extracted with 1N NaOH and water. Pentane was added to induce precipitation of a white solid that was again filtered away. The filtrate was concentrated in vacuo, and dissolved in methanol (60 mL). Triethylamine (27 grams, 0.267 mol) and propanedithiol (23 grams, 0.215 mol) were added and the mixture stirred at room temperature overnight. The solution was diluted with 100 mL water and partitioned between methylene chloride and 1N NaOH. The organic layer was extracted with 2×200 mL 1N HCl and the aqueous layer washed with 100 mL methylene chloride, made basic with 2N NaOH and extracted 3×75 mL methylene chloride. The combined organics were dried over sodium carbonate, filtered and concentrated in vacuo to yield 12.97 grams of 2-(4-iodophenoxy)ethyl amine (72%). 1NMR (CDCl3, dTMS) 7.56 (2H, d, 3JHH =9 Hz, Ar-H), 6.63 (2H, d, 3JHH =9 Hz, Ar-H), 4.03 (2H, t, 3JHH =5 Hz, CH2N3), 3.57 (2H, t, 3JHH =5 Hz, OCH2). 13C NMR (CDCl3) 158.0, 138.2, 116.9, 83.4, 66.9, 49.9. IR (NaCl, cm-1) 2930, 2107 (s), 1589, 1483, 1284, 1237, 1058, 819. concentrated in vacuo diluted with 90 mL ethyl acetate diluted with hexane (400 mL) the resulting solids filtered away The filtrate was concentrated in vacuo diluted with diethyl ether extracted with 1N NaOH and water Pentane was added precipitation of a white solid that was again filtered away The filtrate was concentrated in vacuo dissolved in methanol (60 mL) the mixture stirred at room temperature overnight partitioned between methylene chloride and 1N NaOH The organic layer was extracted with 2×200 mL 1N HCl the aqueous layer washed with 100 mL methylene chloride extracted 3×75 mL methylene chloride The combined organics were dried over sodium carbonate filtered concentrated in vacuo