1-(difluoromethoxy)-4-iodobenzene

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

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

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

Procedure: A solution of 15.3 g of 4-(trans-4-pentylcyclohexyl)phenylacetylene (available from the acetophenone by dehydration, using PCl5 /KOT), 16.2 g of difluoromethoxy-4-iodobenzene, 100 ml of triethylamine, 0.085 g of bis(triphenylphosphine)dichloropalladium and 0.11 g of copper(I) iodide is stirred at room temperature for 3 hours. The cloudy mixture is stirred into dilute hydrochloric acid (500 ml of water +200 ml of 37% hydrochloric acid), extracted with t-butyl methyl ether and worked up as usual. m.p.: 62° C., c.p.: 203.1° C. extracted with t-butyl methyl ether 203.1° C.

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

Procedure: A solution of 15.3 g of 4-(trans-4-pentylcyclohexyl)phenylacetylene (available from the acetophenone by dehydration, using PCl5 /KOT), 16.2 g of difluoromethoxy-4-iodobenzene, 100 ml of triethylamine, 0.085 g of bis(triphenylphosphine)dichloropalladium and 0.11 g of copper(I) iodide is stirred at room temperature for 3 hours. The cloudy mixture is stirred into dilute hydrochloric acid (500 ml of water +200 ml of 37% hydrochloric acid), extracted with t-butyl methyl ether and worked up as usual. m.p.: 62° C., c.p.: 203.1° C. extracted with t-butyl methyl ether 203.1° C.

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

Procedure: 100 g (0.455 mol) of 4-iodophenol and 54.6 g (1.365 mol) of sodium hydroxide are added to a mixture of 300 ml of THF and 30 ml of water. After stirring for about 1/2 hour, the mixture is evaporated in a rotary evaporator; this is repeated after the addition of 200 ml of toluene. The residue is taken up in 400 ml of THF. The mixture is cooled to 0° C., 47.1 g (0.545 mol) of chlorodifluoromethane are introduced, and the mixture is then stirred for 1 hour. It is then stirred at about +5° C. for 18 hours. The solution above the resulting slurry-like precipitate was decanted off. It was evaporated in a rotary evaporator, and the residue was chromatographed through a silica gel column, using petroleum ether as eluent. the mixture is evaporated in a rotary evaporator after the addition of 200 ml of toluene the mixture is then stirred for 1 hour It is then stirred at about +5° C. for 18 hours The solution above the resulting slurry-like precipitate was decanted off It was evaporated in a rotary evaporator the residue was chromatographed through a silica gel column

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

Procedure: 100 g (0.455 mol) of 4-iodophenol and 54.6 g (1.365 mol) of sodium hydroxide are added to a mixture of 300 ml of THF and 30 ml of water. After stirring for about 1/2 hour, the mixture is evaporated in a rotary evaporator; this is repeated after the addition of 200 ml of toluene. The residue is taken up in 400 ml of THF. The mixture is cooled to 0° C., 47.1 g (0.545 mol) of chlorodifluoromethane are introduced, and the mixture is then stirred for 1 hour. It is then stirred at about +5° C. for 18 hours. The solution above the resulting slurry-like precipitate was decanted off. It was evaporated in a rotary evaporator, and the residue was chromatographed through a silica gel column, using petroleum ether as eluent. the mixture is evaporated in a rotary evaporator after the addition of 200 ml of toluene the mixture is then stirred for 1 hour It is then stirred at about +5° C. for 18 hours The solution above the resulting slurry-like precipitate was decanted off It was evaporated in a rotary evaporator the residue was chromatographed through a silica gel column

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

Procedure: A solution of 1-(difluoromethoxy)-4-iodobenzene (12.7 g, 50 mmol) in triethylamine is treated with tetrakis(triphenylphosphine)palladium (4.0 g, 3.5 mmol), copper iodide (925 mg, 4.85 mmol), and a solution of ethynyl(trimethyl)silane (6.9 mL, 50 mmol) in acetonitrile at room temperature, stirred for 1 h at 60° C. and concentrated in vacuo. The resultant residue was dissolved in Et2O and filtered. The filtrate was concentrated and the concentrate was purified by chromatography (silica gel, EtOAc/hexane: 5/95) to give {[4-(difluoromethoxy)phenyl]ethynyl}(trimethyl)silane (11.5 g, 96%) as an oil. concentrated in vacuo The resultant residue was dissolved in Et2O filtered The filtrate was concentrated the concentrate was purified by chromatography (silica gel, EtOAc/hexane: 5/95)

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

Procedure: A solution of 1-(difluoromethoxy)-4-iodobenzene (12.7 g, 50 mmol) in triethylamine is treated with tetrakis(triphenylphosphine)palladium (4.0 g, 3.5 mmol), copper iodide (925 mg, 4.85 mmol), and a solution of ethynyl(trimethyl)silane (6.9 mL, 50 mmol) in acetonitrile at room temperature, stirred for 1 h at 60° C. and concentrated in vacuo. The resultant residue was dissolved in Et2O and filtered. The filtrate was concentrated and the concentrate was purified by chromatography (silica gel, EtOAc/hexane: 5/95) to give {[4-(difluoromethoxy)phenyl]ethynyl}(trimethyl)silane (11.5 g, 96%) as an oil. concentrated in vacuo The resultant residue was dissolved in Et2O filtered The filtrate was concentrated the concentrate was purified by chromatography (silica gel, EtOAc/hexane: 5/95)

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

Procedure: In a departure from the procedure described above the compound is prepared from 4-difluoromethoxy-1-iodo-benzene using iPrMgCl to generate the arylmetal compound and trapping this intermediate with trimethyl borate.

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

Procedure: In a departure from the procedure described above the compound is prepared from 4-difluoromethoxy-1-iodo-benzene using iPrMgCl to generate the arylmetal compound and trapping this intermediate with trimethyl borate.

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

Procedure: Prepared as described for 3,4-bis(benzyloxy)-6-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}pyridazine (Intermediate 6) from 3,4-bis(benzyloxy)-6-ethynylpyridazine (Intermediate 5) and 1-(difluoromethoxy)-4-iodobenzene in 58% yield. Prepared

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

Procedure: A solution of 1-(difluoromethoxy)-4-iodobenzene (12.7 g, 50 mmol) in triethylamine (175 mL) was treated with tetrakis(triphenylphosphine)palladium (4.0 g, 3.5 mmol), copper iodide (925 mg, 4.85 mmol), and a solution of ethynyl(trimethyl)silane (6.9 mL, 50 mmol) in acetonitrile at room temperature, stirred for 1 h at 60° C. and concentrated in vacuo. The resultant residue was dissolved in Et2O, filtered and the filtrated was concentrated in vacuo. This residue was purified by chromatography (silica gel, EtOAc/hexane:5/95) to give {[4-(difluoromethoxy)-phenyl]ethynyl}(trimethyl)silane (11.5 g, 96%) as an oil. concentrated in vacuo The resultant residue was dissolved in Et2O filtered the filtrated was concentrated in vacuo This residue was purified by chromatography (silica gel, EtOAc/hexane:5/95)