4-tert-butyl-2-iodophenol

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a freshly prepared solution of 2-iodo-4-(1,1-dimethylethyl)phenol (5.5 g., 0.02 mole) in a mixture of acetic acid (27 ml.) and sulfuric acid (3 ml.) is added powdered 2-chloro-N-(hydroxymethyl)acetamide (2.5 g., 0.02 mole) with stirring at 20° C. over a 10 minute period. After 2.5 hours the orange solution is poured into water (200 ml.). The 2-chloro-N-[2-hydroxy-3-iodo-5-(1,1-dimethylethyl)benzyl]-acetamide which precipitates is collected, dried by suction and dissolved in ethanol (75 ml.). Concentrated hydrochloric acid (15 ml.) is added and the mixture is refluxed for two hours. The mixture is concentrated to one-half its original volume and allowed to cool. The resulting precipitate (1.4 g.), which is unhydrolyzed 2-chloro-N-[2-hydroxy-3-iodo-5-(1,1-dimethylethyl)benzyl]acetamide, is collected. The filtrate is concentrated to 25 ml. and, upon cooling, crude 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride (4 g.) separates which upon crystallization from a mixture of ethanol and ether affords substantially pure 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride (2.5 g.), m.p. 200°-201° (dec.). The 2-chloro-N-[2-hydroxy-3-iodo-5-(1,1-dimethylethyl)benzyl]-acetamide which precipitates is collected dried by suction dissolved in ethanol (75 ml.) Concentrated hydrochloric acid (15 ml.) is added the mixture is refluxed for two hours The mixture is concentrated to one-half its original volume to cool is collected The filtrate is concentrated to 25 ml and, upon cooling upon crystallization from a mixture of ethanol and ether

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

Procedure: A solution of 4-t-butyl-2-iodophenol [38941-98-9] (1.0 g, 3.6 mmol), 4-Methoxyphenylacetylene (0.53 g, 4.0 mmol), PdCl2P(PH3)2 (70 mg), and CuI (50 mg) in DMF/Diethylamine (10 ml) was heated to 60° C. After 1 hr, the reaction was cooled and poured into water which was extracted with EtOAc. The organic layer was dried, concentrated to give a solid which was triturated with MeOH, filtered to give 84 as a solid. the reaction was cooled was extracted with EtOAc The organic layer was dried concentrated to give a solid which was triturated with MeOH filtered

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

Procedure: A solution of 4-t-butyl-2-iodophenol [38941-98-9] (1.09 g, 3.6 mmol), 4-Methoxyphenylacetylene (0.53 g, 4.0 mmol), PdCl2P(PH3)2 (70 mg), and Cul (50 mg) in DMF/Diethylamine (10 ml) was heated to 60° C. After 1 hr, the reaction was cooled and poured into water which was extracted with EtOAc. The organic layer was dried, concentrated to give a solid which was triturated with MeOH, filtered to give 84 as a solid. the reaction was cooled was extracted with EtOAc The organic layer was dried concentrated to give a solid which was triturated with MeOH filtered

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

Procedure: The general procedure was used to convert phenylacetylene and 4-tert-Butyl-2-iodophenol to the title product. Purification by flash chromatography (10% ethyl acetate in hexanes as the eluent) gave the analytically pure product as a white solid (398 mg, 80% yield). 1H NMR (300 MHz, CDCl3) δ 7.83 (dd, J=7.16, 2H), 7.57-7.56 (m, 1H), 7.44-7.38 (m, 3H), 7.34-7.30 (m, 2H), 6.96 (s, 1H), 1.38 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 155.99, 153.12, 145.92, 130.65, 128.88, 128.72, 128.33, 124.82, 122.23, 117.06, 110.42, 101.48, 34.68, 31.83. Anal. Calcd. for C18H18O: C, 86.36; H, 7.25. Found C, 86.34; H, 7.13. m.p.: 103-104° C. (lit., 7102-103° C.).

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a freshly prepared solution of 2-iodo-4-(1,1-dimethylethyl)phenol (5.5 g., 0.02 mole) in a mixture of acetic acid (27 ml.) and sulfuric acid (3 ml.) is added powdered 2-chloro-N-(hydroxymethyl)acetamide (2.5 g., 0.02 mole) with stirring at 20° C. over a 10 minute period. After 2.5 hours the orange solution is poured into water (200 ml.). The 2-chloro-N-[2-hydroxy-3-iodo-5-(1,1-dimethylethyl)benzyl]-acetamide which precipitates is collected, dried by suction and dissolved in ethanol (75 ml.). Concentrated hydrochloric acid (15 ml.) is added and the mixture is refluxed for two hours. The mixture is concentrated to one-half its original volume and allowed to cool. The resulting precipitate (1.4 g.), which is unhydrolyzed 2-chloro-N-[2-hydroxy-3-iodo-5-(1,1-dimethylethyl)benzyl]acetamide, is collected. The filtrate is concentrated to 25 ml. and, upon cooling, crude 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride (4 g.) separates which upon crystallization from a mixture of ethanol and ether affords substantially pure 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride (2.5 g.), m.p. 200°-201° (dec.). The 2-chloro-N-[2-hydroxy-3-iodo-5-(1,1-dimethylethyl)benzyl]-acetamide which precipitates is collected dried by suction dissolved in ethanol (75 ml.) Concentrated hydrochloric acid (15 ml.) is added the mixture is refluxed for two hours The mixture is concentrated to one-half its original volume to cool is collected The filtrate is concentrated to 25 ml and, upon cooling upon crystallization from a mixture of ethanol and ether