1-fluoro-4-iodo-2-Methoxybenzene

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:0.00; pressure:0.00; stir:

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

Procedure: Dissolve 1-fluoro-4-iodo-2-methoxybenzene, (prepared as described in PREPARATION 47), (480 mg, 1.9 mmol) in triethylamine (7 mL, 53 mmol) and add 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1.8 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (51 mg, 0.07 mmol) and copper (I) iodide (28 mg, 0.15 mmol). Stir for 18 h at room temperature, concentrate, and purify by silica gel chromatography, eluting with 3:1 hexanes:ethyl acetate. Further purify on silica gel, eluting with 100% dichloromethane, to give the title compound as a white solid (450 mg, 94%). concentrate purify by silica gel chromatography eluting with 3:1 hexanes Further purify on silica gel eluting with 100% dichloromethane

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

Procedure: Dissolve 1-fluoro-4-iodo-2-methoxybenzene, (prepared as described in PREPARATION 47), (480 mg, 1.9 mmol) in triethylamine (7 mL, 53 mmol) and add 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1.8 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (51 mg, 0.07 mmol) and copper (I) iodide (28 mg, 0.15 mmol). Stir for 18 h at room temperature, concentrate, and purify by silica gel chromatography, eluting with 3:1 hexanes:ethyl acetate. Further purify on silica gel, eluting with 100% dichloromethane, to give the title compound as a white solid (450 mg, 94%). concentrate purify by silica gel chromatography eluting with 3:1 hexanes Further purify on silica gel eluting with 100% dichloromethane

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

Procedure: Dissolve 1-fluoro-4-iodo-2-methoxybenzene, (prepared as described in PREPARATION 47), (1.0 g, 4.0 mmol) in triethylamine (15 mL, 108 mmol) and add 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (500 mg, 3.8 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (100 mg, 0.14 mmol) and copper (I) iodide (60 mg, 0.32 mmol). Stir for 18 h at room temperature, concentrate and purify by silica gel chromatography, eluting with 3:1 hexanes:ethyl acetate. Further purify on silica gel, eluting with 9:1 dichloromethane:ethyl acetate, to give the title compound as a white solid (650 mg, 65%). concentrate purify by silica gel chromatography eluting with 3:1 hexanes Further purify on silica gel eluting with 9:1 dichloromethane

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

Procedure: Dissolve 4-fluoro-3-methoxyphenylamine (5.0 g, 35 mmol) in water (25 mL) and concentrated sulfuric acid (8 mL). Cool to less than 0° C. in an ice/methanol bath and add sodium nitrite (2.7 g, 39 mmol) dropwise in a solution in water (20 mL) and stir one h. Dissolve potassium iodide (9.9 g, 60 mmol) in water (35 mL) and add dropwise. Warm to room temperature and stir 18 h. Extract with ethyl acetate (300 mL), wash with water (200 mL), saturated aqueous sodium thiosulfate (300 mL), and saturated aqueous sodium chloride (300 mL). Dry (sodium sulfate), filter, and concentrate to give the title compound as an orange oil (8.8 g, 99%). Cool to less than 0° C. in an ice/methanol bath stir 18 h Extract with ethyl acetate (300 mL) wash with water (200 mL), saturated aqueous sodium thiosulfate (300 mL), and saturated aqueous sodium chloride (300 mL) Dry (sodium sulfate) filter concentrate

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

Procedure: Dissolve 1-fluoro-4-iodo-2-methoxybenzene, (prepared as described in PREPARATION 47), (480 mg, 1.9 mmol) in triethylamine (7 mL, 53 mmol) and add 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1.8 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (51 mg, 0.07 mmol) and copper (I) iodide (28 mg, 0.15 mmol). Stir for 18 h at room temperature, concentrate, and purify by silica gel chromatography, eluting with 3:1 hexanes:ethyl acetate. Further purify on silica gel, eluting with 100% dichloromethane, to give the title compound as a white solid (450 mg, 94%). concentrate purify by silica gel chromatography eluting with 3:1 hexanes Further purify on silica gel eluting with 100% dichloromethane

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

Procedure: Dissolve 1-fluoro-4-iodo-2-methoxybenzene, (prepared as described in PREPARATION 47), (1.0 g, 4.0 mmol) in triethylamine (15 mL, 108 mmol) and add 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (500 mg, 3.8 mmol) followed by bis(triphenylphosphine)palladium (II) dichloride (100 mg, 0.14 mmol) and copper (I) iodide (60 mg, 0.32 mmol). Stir for 18 h at room temperature, concentrate and purify by silica gel chromatography, eluting with 3:1 hexanes:ethyl acetate. Further purify on silica gel, eluting with 9:1 dichloromethane:ethyl acetate, to give the title compound as a white solid (650 mg, 65%). concentrate purify by silica gel chromatography eluting with 3:1 hexanes Further purify on silica gel eluting with 9:1 dichloromethane

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

Procedure: Dissolve 4-fluoro-3-methoxyphenylamine (5.0 g, 35 mmol) in water (25 mL) and concentrated sulfuric acid (8 mL). Cool to less than 0° C. in an ice/methanol bath and add sodium nitrite (2.7 g, 39 mmol) dropwise in a solution in water (20 mL) and stir one h. Dissolve potassium iodide (9.9 g, 60 mmol) in water (35 mL) and add dropwise. Warm to room temperature and stir 18 h. Extract with ethyl acetate (300 mL), wash with water (200 mL), saturated aqueous sodium thiosulfate (300 mL), and saturated aqueous sodium chloride (300 mL). Dry (sodium sulfate), filter, and concentrate to give the title compound as an orange oil (8.8 g, 99%). Cool to less than 0° C. in an ice/methanol bath stir 18 h Extract with ethyl acetate (300 mL) wash with water (200 mL), saturated aqueous sodium thiosulfate (300 mL), and saturated aqueous sodium chloride (300 mL) Dry (sodium sulfate) filter concentrate