2,2,2-trifluoro-N-(4-iodophenyl)acetamide

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

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

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

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,2,2-trifluoro-N-(4-iodophenyl)acetamide (3.2 g, 10 mmol, prepared according to Melissaris, A. P. and Litt, M. H. J Org Chem 1994, 59, 5818-5821), dichlorobis(triphenylphosphine)palladium(II) (0.14 g, 0.2 mmol), triphenylphosphine (19 mg, 0.07 mmol), and copper (I) iodide (0.019 g, 0.1 mmol) in triethylamine (50 mL) was degassed under Argon for 10 minutes while stirring in a 55° C. oil bath. The mixture was then treated with 5-chloropentyne (1.1 mL, 10 mmol). After four hours of heating, the mixture was allowed to cool to room temperature and was then filtered through a pad of Celite diatomaceous earth. The filtrate was concentrated under reduced pressure to provide the crude title compound, which was carried forward without further purification. ES/MS calcd. for C14H14ClF3NO+ : 290.1. found m/z=290.1 (M+H)+ prepared After four hours of heating to cool to room temperature was then filtered through a pad of Celite diatomaceous earth The filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,2,2-trifluoro-N-(4-iodophenyl)acetamide (3.2 g, 10 mmol, prepared according to Melissaris, A. P. and Litt, M. H. J Org Chem 1994, 59, 5818-5821), dichlorobis(triphenylphosphine)palladium(II) (0.14 g, 0.2 mmol), triphenylphosphine (19 mg, 0.07 mmol), and copper (I) iodide (0.019 g, 0.1 mmol) in triethylamine (50 mL) was degassed under Argon for 10 minutes while stirring in a 55° C. oil bath. The mixture was then treated with 5-chloropentyne (1.1 mL, 10 mmol). After four hours of heating, the mixture was allowed to cool to room temperature and was then filtered through a pad of Celite diatomaceous earth. The filtrate was concentrated under reduced pressure to provide the crude title compound, which was carried forward without further purification. ES/MS calcd. for C14H14ClF3NO+ : 290.1. found m/z=290.1 (M+H)+ prepared After four hours of heating to cool to room temperature was then filtered through a pad of Celite diatomaceous earth The filtrate was concentrated under reduced pressure

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: Part B: The above-obtained amide was dissolved in acetone (80 mL), to which potassium carbonate (15.75 g, 114.1 mmol) and iodomethane (9.6 mL, 114.1 mmol) were added. The reaction was heated to reflux for 2 hours and cooled, and the resulting solid was filtered. The solvent was removed from the filtrate. The residue was dissolved in dichloromethane, washed with water and brine, and dried over sodium sulfate. After filtration and removal of solvent, the solid was further dried in vacuo to give the desired 2,2,2-trifluoro-N-(4-iodo-phenyl)-N-methyl-acetamide as a white solid. MS found: (M+1)+=330.05. were added The reaction was heated to reflux for 2 hours cooled the resulting solid was filtered The solvent was removed from the filtrate The residue was dissolved in dichloromethane washed with water and brine dried over sodium sulfate After filtration and removal of solvent the solid was further dried in vacuo

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,2,2-trifluoro-N-(4-iodophenyl)acetamide (3.2 g, 10 mmol, prepared according to Melissaris, A. P. and Litt, M. H. J Org Chem 1994, 59, 5818-5821), dichlorobis(triphenylphosphine)palladium(II) (0.14 g, 0.2 mmol), triphenylphosphine (19 mg, 0.07 mmol), and copper (I) iodide (0.019 g, 0.1 mmol) in triethylamine (50 mL) was degassed under Argon for 10 minutes while stirring in a 55° C. oil bath. The mixture was then treated with 5-chloropentyne (1.1 mL, 10 mmol). After four hours of heating, the mixture was allowed to cool to room temperature and was then filtered through a pad of Celite diatomaceous earth. The filtrate was concentrated under reduced pressure to provide the crude title compound, which was carried forward without further purification. ES/MS calcd. for C14H14ClF3NO+: 290.1, found m/z=290.1 (M+H)+ prepared After four hours of heating to cool to room temperature was then filtered through a pad of Celite diatomaceous earth The filtrate was concentrated under reduced pressure

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

Procedure: The title compound was synthesized in a manner analogous to that described for Intermediate 32, using Intermediate 43 as a substrate. ES/MS calcd. for C13H14BrF3NO2+ 352.0. Found m/z=352.1 (M+H)+.

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

Procedure: A solution of Intermediate 32 (2.7 g, 8.5 mmol, prepared according to Melissaris, A. P. and Litt, M. H. J Org Chem 1994, 59, 5818-5821) in DMF (26 mL) was treated successively with tetra-n-butylammonium acetate (3.8 g, 13 mmol) and palladium (II) acetate (57 mg, 0.26 mmol). The mixture was degassed with nitrogen and then treated with 5-hexyn-1-ol (0.93 mL, 8.5 mmol). After four hours of stirring at room temperature, additional quantities of the following reagents were added: tetra-n-butylammonium acetate (1 g), palladium (II) acetate (57 mg), and 5-hexyn-1-ol (1 mL). After stirring overnight at room temperature, the mixture was partitioned between diethyl ether and water. The aqueous phase was extracted four times with diethyl ether. The combined organic extracts were washed twice with water and once with saturated aqueous sodium chloride solution before drying over anhydrous magnesium sulfate, filtration and concentration under reduced pressure to provide the title compound as brown syrup that partially solidified under vacuum. ES/MS calcd. for C14H15F3NO2+: 286.1. Found m/z=286.2 (M+H)+ The mixture was degassed with nitrogen additional quantities of the following reagents were added After stirring overnight at room temperature the mixture was partitioned between diethyl ether and water The aqueous phase was extracted four times with diethyl ether The combined organic extracts were washed twice with water and once with saturated aqueous sodium chloride solution before drying over anhydrous magnesium sulfate, filtration and concentration under reduced pressure

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

Procedure: The title compound was synthesized in a manner analogous to that described in Intermediate 32, using 4-iodo-3-methylaniline as a substrate. ES/MS calcd. for C9H7F3INO 328.95. Found m/z=330 (M+H)+.