1-fluoro-4-iodo-2-(trifluoromethyl)benzene

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 mixture of 2-fluoro-5-iodobenzotrifluoride (5.00 g), copper(I) iodide (65.5 mg), triphenylphosphine (226 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (356 mg), propargyl alcohol (1.12 ml), diisopropylethylamine (12.0 ml) and tetrahydrofuran (80 ml) was stirred at room temperature for 11 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20) to give the object product (3.26 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sequentially add 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (300 mg, 2.2 mmol), (bis(triphenylphosphine)palladium (II) dichloride (69 mg, 0.10 mmol), and copper (I) iodide (38 mg, 0.198 mmol) to a solution of 1-fluoro-4-iodo-2-trifluoromethylbenzene (575 mg, 1.98 mmol) in triethylamine (4 mL) under nitrogen. Heat at 70° C. for 2.5 h and concentrate. Purify the residue by silica gel chromatography, eluting from 0:100 to 20:80 using ethyl acetate:hexanes, to give the title compound as a white solid (520 mg, 88%). concentrate Purify the residue by silica gel chromatography eluting from 0:100 to 20:80 using ethyl acetate

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sequentially add 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (300 mg, 2.2 mmol), (bis(triphenylphosphine)palladium (II) dichloride (69 mg, 0.10 mmol), and copper (I) iodide (38 mg, 0.198 mmol) to a solution of 1-fluoro-4-iodo-2-trifluoromethylbenzene (575 mg, 1.98 mmol) in triethylamine (4 mL) under nitrogen. Heat at 70° C. for 2.5 h and concentrate. Purify the residue by silica gel chromatography, eluting from 0:100 to 20:80 using ethyl acetate:hexanes, to give the title compound as a white solid (520 mg, 88%). concentrate Purify the residue by silica gel chromatography eluting from 0:100 to 20:80 using ethyl acetate

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 1-fluoro-4-iodo-2-trifluoromethylbenzene (813 mg, 2.8 mmol) in triethylamine (6 mL). Add 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (400 mg, 3.0 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (0.100 g, 0.14 mmol) and copper (I) iodide (53 mg, 0.28 mmol). Heat at 70° C. for 16 h, concentrate, and purify using silica gel chromatography, eluting with 100:0 to 90:10 methylene chloride:ethyl acetate, to give the title compound as a pale yellow solid (820 mg, 99%). concentrate purify eluting with 100:0 to 90:10 methylene chloride

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 1-fluoro-4-iodo-2-trifluoromethylbenzene (813 mg, 2.8 mmol) in triethylamine (6 mL). Add 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (400 mg, 3.0 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (0.100 g, 0.14 mmol) and copper (I) iodide (53 mg, 0.28 mmol). Heat at 70° C. for 16 h, concentrate, and purify using silica gel chromatography, eluting with 100:0 to 90:10 methylene chloride:ethyl acetate, to give the title compound as a pale yellow solid (820 mg, 99%). concentrate purify eluting with 100:0 to 90:10 methylene chloride

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

Procedure: A mixture of 2-fluoro-5-iodobenzotrifluoride (5.00 g), copper(I) iodide (65.5 mg), triphenylphosphine (226 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (356 mg), propargyl alcohol (1.12 ml), diisopropylethylamine (12.0 ml) and tetrahydrofuran (80 ml) was stirred at room temperature for 11 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20) to give the object product (3.26 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sequentially add 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (300 mg, 2.2 mmol), (bis(triphenylphosphine)palladium (II) dichloride (69 mg, 0.10 mmol), and copper (I) iodide (38 mg, 0.198 mmol) to a solution of 1-fluoro-4-iodo-2-trifluoromethylbenzene (575 mg, 1.98 mmol) in triethylamine (4 mL) under nitrogen. Heat at 70° C. for 2.5 h and concentrate. Purify the residue by silica gel chromatography, eluting from 0:100 to 20:80 using ethyl acetate:hexanes, to give the title compound as a white solid (520 mg, 88%). concentrate Purify the residue by silica gel chromatography eluting from 0:100 to 20:80 using ethyl acetate

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 1-fluoro-4-iodo-2-trifluoromethylbenzene (813 mg, 2.8 mmol) in triethylamine (6 mL). Add 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (400 mg, 3.0 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (0.100 g, 0.14 mmol) and copper (I) iodide (53 mg, 0.28 mmol). Heat at 70° C. for 16 h, concentrate, and purify using silica gel chromatography, eluting with 100:0 to 90:10 methylene chloride:ethyl acetate, to give the title compound as a pale yellow solid (820 mg, 99%). concentrate purify eluting with 100:0 to 90:10 methylene chloride