4-fluoro-2-iodophenol

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 15.00 g (63.03 mmol) of 4-fluoro-2-iodophenol (P7), Preparation 7 and 6.40 g (31.68 mmol) of 1,3-dibromopropane in 200 mL of acetone add 26.00 g (188.4 mmol) of potassium carbonate. Reflux the resulting reaction mixture for 24 hours. Cool the reaction mixture to room temperature, filter it, and concentrate the filtrate by rotary evaporation. Crystallize the resulting solid from acetonitrile to yield 12.00 g (74%) of (P8) as a white crystalline solid. Reflux the resulting reaction mixture for 24 hours filter it concentrate the filtrate by rotary evaporation Crystallize the resulting solid from acetonitrile to yield 12.00 g (74%) of (P8) as a white crystalline solid

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 16.8 g (150 millimoles (mmol) of 4-fluorophenol in 300 mL of methanol at 0° C., add 22.5 g (150 mmol) of NaI and 6.00 g (150 mmol) of NaOH. To the resulting mixture add 258 mL of 5% aqueous NaOCl solution (commercial bleach) over a one hour period. Stir the resulting slurry for one more hour at 0° C. Add 90 mL of 10% aqueous Na2S2O3 solution, and acidify the resulting reaction mixture by adding dilute hydrochloric acid. Extract the resulting mixture with methylene chloride, wash the resulting organic layer with brine and dry it over anhydrous magnesium sulfate. Remove solvent, dissolve the residue in hot hexanes, and allow the resulting solution to stand in a freezer for two hours. A dark colored material oils out. Decant the solution away therefrom and allow the resulting colorless decanted solution to stand in a freezer for 18 hours. Filter off the resulting white crystals and dry them under reduced pressure to yield 18.00 g (50%) of pure 4-fluoro-2-iodophenol (P7) as a white solid. the resulting reaction mixture Extract the resulting mixture with methylene chloride wash the resulting organic layer with brine dry it over anhydrous magnesium sulfate Remove solvent, dissolve the residue in hot hexanes Decant the solution away to stand in a freezer for 18 hours Filter off the resulting white crystals dry them under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-4-fluorobenzenesulfonamide (Preparation 52, 100 mg, 0.32 mmol) and potassium carbonate (109 mg, 0.8 mmol) in dimethylformamide (3 ml) was added 4-fluoro-2-iodophenol (Preparation 218, 0.32 mmol) and the reaction heated at 80° C. for 24 hours. The solution was added dropwise into rapidly stirring hydrochloric acid (2M aqueous solution). The fine dark precipitate was filtered and dried in vacuo to afford the title product as a brown solid, 100 mg, 59% yield. The fine dark precipitate was filtered dried in vacuo

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

Procedure: N-Iodosuccinimide (10 g, 45.0 mmol) and 4-fluoro-phenol (5.00 g, 40.0 mmol) were suspended in acetic acid (39 ml, 649.0 mmol) and stirred for 5 minutes before addition of concentrated sulphuric acid (0.79 ml, 13.4 mmol). The reaction mixture was stirred for 18 hours at room temperature before diluting with water (100 ml). The aqueous layer was extracted with dichloromethane (2×30 ml). The combined organic extracts were washed with sodium thiosulphate solution (20% aqueous, wt:v), water, dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by column chromatography (silica gel) eluting with toluene to afford the title compound as an off white solid, 4.5 g, 40% yield. The aqueous layer was extracted with dichloromethane (2×30 ml) The combined organic extracts were washed with sodium thiosulphate solution (20% aqueous, wt:v), water dried over sodium sulfate filtered concentrated in vacuo The crude residue was purified by column chromatography (silica gel) eluting with toluene

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

Procedure: N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-N-(2,4-dimethoxybenzyl)-4-fluorobenzenesulfonamide (Preparation 207, 410 mg, 0.876 mmol), 2-iodo-4-fluorophenol (Preparation 218, 229 mg, 0.964 mmol) and potassium carbonate (363 mg, 2.63 mmol) in dimethyl sulphoxide (20 ml) were stirred at room temperature under nitrogen for 18 hours. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate (3×30 ml). The combined organics were washed with saturated aqueous sodium chloride solution (30 ml), dried over magnesium sulfate, filtered and concentrated in vacuo to give the title compound as an off-white solid, 670 mg, quantitative yield. extracted with ethyl acetate (3×30 ml) The combined organics were washed with saturated aqueous sodium chloride solution (30 ml) dried over magnesium sulfate filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-4-fluorobenzenesulfonamide (Preparation 52, 100 mg, 0.32 mmol) and potassium carbonate (109 mg, 0.8 mmol) in dimethylformamide (3 ml) was added 4-fluoro-2-iodophenol (Preparation 218, 0.32 mmol) and the reaction heated at 80° C. for 24 hours. The solution was added dropwise into rapidly stirring hydrochloric acid (2M aqueous solution). The fine dark precipitate was filtered and dried in vacuo to afford the title product as a brown solid, 100 mg, 59% yield. The fine dark precipitate was filtered dried in vacuo

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

Procedure: N-Iodosuccinimide (10 g, 45.0 mmol) and 4-fluoro-phenol (5.00 g, 40.0 mmol) were suspended in acetic acid (39 ml, 649.0 mmol) and stirred for 5 minutes before addition of concentrated sulphuric acid (0.79 ml, 13.4 mmol). The reaction mixture was stirred for 18 hours at room temperature before diluting with water (100 ml). The aqueous layer was extracted with dichloromethane (2×30 ml). The combined organic extracts were washed with sodium thiosulphate solution (20% aqueous, wt:v), water, dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by column chromatography (silica gel) eluting with toluene to afford the title compound as an off white solid, 4.5 g, 40% yield. The aqueous layer was extracted with dichloromethane (2×30 ml) The combined organic extracts were washed with sodium thiosulphate solution (20% aqueous, wt:v), water dried over sodium sulfate filtered concentrated in vacuo The crude residue was purified by column chromatography (silica gel) eluting with toluene

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

Procedure: N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-N-(2,4-dimethoxybenzyl)-4-fluorobenzenesulfonamide (Preparation 207, 410 mg, 0.876 mmol), 2-iodo-4-fluorophenol (Preparation 218, 229 mg, 0.964 mmol) and potassium carbonate (363 mg, 2.63 mmol) in dimethyl sulphoxide (20 ml) were stirred at room temperature under nitrogen for 18 hours. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate (3×30 ml). The combined organics were washed with saturated aqueous sodium chloride solution (30 ml), dried over magnesium sulfate, filtered and concentrated in vacuo to give the title compound as an off-white solid, 670 mg, quantitative yield. extracted with ethyl acetate (3×30 ml) The combined organics were washed with saturated aqueous sodium chloride solution (30 ml) dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: A solution of 4-Fluoro-2-Iodophenol [2713-29-3] (0.9 g, 3.8 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 over MgSO4, filtered and concentrated to give a solid which was triturated with MeOH, and filtered to give 83 as a solid. the reaction was cooled was extracted with EtOAc The organic layer was dried over MgSO4 filtered concentrated to give a solid which was triturated with MeOH filtered

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-4-fluorobenzenesulfonamide (Preparation 52, 100 mg, 0.32 mmol) and potassium carbonate (109 mg, 0.8 mmol) in dimethylformamide (3 ml) was added 4-fluoro-2-iodophenol (Preparation 218, 0.32 mmol) and the reaction heated at 80° C. for 24 hours. The solution was added dropwise into rapidly stirring hydrochloric acid (2M aqueous solution). The fine dark precipitate was filtered and dried in vacuo to afford the title product as a brown solid, 100 mg, 59% yield. The fine dark precipitate was filtered dried in vacuo