1-fluoro-2-(4-iodophenoxy)benzene

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

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

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

Procedure: Add isoamylnitrite (2.45 g, 2.5 Eq.) to 4-(2-fluoro-phenoxy)-phenylamine (1.70 g, 8.37 mmol) and diiodomethane (7.84 g, 3.5 Eq.) in acetonitrile (10 mL) while stirring at 55° C. under a nitrogen atmosphere. Slowly heat mixture to 75° C. and heat at this temperature for 3 hours. Cool to room temperature and pour into water, and extract the desired material into ethyl acetate. Wash this organic layer once with water, dry over potassium carbonate, filter, and concentrate under reduced vacuum to give 2.41 g of an oil. Purify the material by silica gel chromatography (Prep. 2000) eluting with hexane/methylene chloride 9:1 to provide 1.60 g of the title compound as a thin oil. Mass spectrum (m/e): 314.0 (M*): (Bruker 300) 1H NMR (CDCl3) δ 7.55-7.60 (2H, d), 7.02-7.20 (4H, m), 6.69-6.72 (2H, d). Slowly heat mixture to 75° C. and heat at this temperature for 3 hours Cool to room temperature extract the desired material into ethyl acetate Wash this organic layer once with water dry over potassium carbonate filter concentrate under reduced vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed a solution of 1-(2-fluorophenoxy)-4-iodobenzene (3.3 g, 10.51 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). n-BuLi (4.4 mL) was added dropwise with stirring at −78° C. The resulting solution was stirred for 10 mins at −78° C. and then tris(propan-2-yl)borate (2.1 g, 11.17 mmol, 1.06 equiv) was added dropwise with stirring at −78° C. over 10 min. The resulting solution was stirred while the temperature warmed from −78° C. to room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl and concentrated under vacuum. The resulting solution was diluted with 10% aquious potassium hydroxide and then washed with ether. The pH of the aqueous was adjusted to 2-4 with hydrogen chloride (37%). The resulting solution was extracted with ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum to give 2.2 g (90%) of [4-(2-fluorophenoxy)phenyl]boronic acid as a white solid Into a 100 mL 3-necked round-bottom flask purged maintained under an inert atmosphere of nitrogen The resulting solution was stirred for 10 mins at −78° C. with stirring at −78° C. over 10 min The resulting solution was stirred while the temperature warmed from −78° C. to room temperature The reaction was then quenched by the addition of saturated aqueous NH4Cl concentrated under vacuum The resulting solution was diluted with 10% aquious potassium hydroxide washed with ether The resulting solution was extracted with ethyl acetate dried over anhydrous sodium sulfate concentrated under vacuum