2-FLUORO-5-IODOPHENYLBORONIC ACID

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

Procedure: To a cooled solution of 2-fluoro-5-iodophenylboronic acid in tetrahydrofuran (200 mL) at 0° C. add an aqueous solution of 30% hydrogen peroxide (9.92 mL, 103 mmol) dropwise, stir 10 min, and add an aqueous 4 N solution of sodium hydroxide (1.78 mL, 7.12 mmol). Warm the reaction to room temperature and stir overnight. Add manganese dioxide (250 mg) to the reaction, stir 90 min and filter through fluted filter paper. Concentrate and partition the residue between diethyl ether and water. Separate the layers and sequentially wash the organic layer with water and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter and concentrate. Purify the resulting tan oil by silica gel chromatography, eluting with a gradient of 0:100 to 30:70 ethyl acetate:hexanes, to give the title compound as a yellow waxy solid (18.1 g, 65%). Warm the reaction to room temperature stir overnight stir 90 min filter through fluted filter paper Concentrate partition the residue between diethyl ether and water Separate the layers sequentially wash the organic layer with water Dry (sodium sulfate) filter concentrate Purify the resulting tan oil by silica gel chromatography eluting with a gradient of 0:100 to 30:70 ethyl acetate

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

Procedure: Add a 2 M solution of n-butyllithium in hexanes (63 mL, 157.5 mmol) to a −20° C. solution of 2,2,6,6-tetramethylpiperidine (28 mL, 165 mmol) in tetrahydrofuran (400 μL). Cool to −78° C. and add 1-iodo-4-fluorobenzene (17.3 mL, 150 mmol) dropwise over 10 min. Stir the reaction mixture at −78° C. for 3 h and add triisopropylborate (40 mL, 172.5 mmol) dropwise over 20 min. Stir for another 30 min and warm the reaction to 40° C. and add of 5 N hydrochloric acid (75 mL). Partition the reaction mixture between diethyl ether (500 mL) and add 1 N hydrochloric acid (500 mL). Separate the organic layer and extract with 2 N sodium hydroxide (400 mL). Make the aqueous layer slightly acidic (pH ˜5-6) by dropwise addition of 5 N hydrochloric acid and collect the resulting white precipitate by filtration. Dry the precipitate overnight under vacuum to provide 2-fluoro-5-iodophenylboronic acid as a white solid, which is used directly without further purification (39g, 98%). Stir for another 30 min warm the reaction to 40° C. Partition the reaction mixture between diethyl ether (500 mL) add 1 N hydrochloric acid (500 mL) Separate the organic layer extract with 2 N sodium hydroxide (400 mL) by dropwise addition of 5 N hydrochloric acid collect the resulting white precipitate by filtration Dry the precipitate overnight under vacuum

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

Procedure: Add a 2 M solution of n-butyllithium in hexanes (63 mL, 157.5 mmol) to a −20° C. solution of 2,2,6,6-tetramethylpiperidine (28 mL, 165 mmol) in tetrahydrofuran (400 μL). Cool to −78° C. and add 1-iodo-4-fluorobenzene (17.3 mL, 150 mmol) dropwise over 10 min. Stir the reaction mixture at −78° C. for 3 h and add triisopropylborate (40 mL, 172.5 mmol) dropwise over 20 min. Stir for another 30 min and warm the reaction to 40° C. and add of 5 N hydrochloric acid (75 mL). Partition the reaction mixture between diethyl ether (500 mL) and add 1 N hydrochloric acid (500 mL). Separate the organic layer and extract with 2 N sodium hydroxide (400 mL). Make the aqueous layer slightly acidic (pH ˜5-6) by dropwise addition of 5 N hydrochloric acid and collect the resulting white precipitate by filtration. Dry the precipitate overnight under vacuum to provide 2-fluoro-5-iodophenylboronic acid as a white solid, which is used directly without further purification (39g, 98%). Stir for another 30 min warm the reaction to 40° C. Partition the reaction mixture between diethyl ether (500 mL) add 1 N hydrochloric acid (500 mL) Separate the organic layer extract with 2 N sodium hydroxide (400 mL) by dropwise addition of 5 N hydrochloric acid collect the resulting white precipitate by filtration Dry the precipitate overnight under vacuum

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

Procedure: To a cooled solution of 2-fluoro-5-iodophenylboronic acid in tetrahydrofuran (200 mL) at 0° C. add an aqueous solution of 30% hydrogen peroxide (9.92 mL, 103 mmol) dropwise, stir 10 min, and add an aqueous 4 N solution of sodium hydroxide (1.78 mL, 7.12 mmol). Warm the reaction to room temperature and stir overnight. Add manganese dioxide (250 mg) to the reaction, stir 90 min and filter through fluted filter paper. Concentrate and partition the residue between diethyl ether and water. Separate the layers and sequentially wash the organic layer with water and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter and concentrate. Purify the resulting tan oil by silica gel chromatography, eluting with a gradient of 0:100 to 30:70 ethyl acetate:hexanes, to give the title compound as a yellow waxy solid (18.1 g, 65%). Warm the reaction to room temperature stir overnight stir 90 min filter through fluted filter paper Concentrate partition the residue between diethyl ether and water Separate the layers sequentially wash the organic layer with water Dry (sodium sulfate) filter concentrate Purify the resulting tan oil by silica gel chromatography eluting with a gradient of 0:100 to 30:70 ethyl acetate

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

Procedure: Add a 2 M solution of n-butyllithium in hexanes (63 mL, 157.5 mmol) to a −20° C. solution of 2,2,6,6-tetramethylpiperidine (28 mL, 165 mmol) in tetrahydrofuran (400 μL). Cool to −78° C. and add 1-iodo-4-fluorobenzene (17.3 mL, 150 mmol) dropwise over 10 min. Stir the reaction mixture at −78° C. for 3 h and add triisopropylborate (40 mL, 172.5 mmol) dropwise over 20 min. Stir for another 30 min and warm the reaction to 40° C. and add of 5 N hydrochloric acid (75 mL). Partition the reaction mixture between diethyl ether (500 mL) and add 1 N hydrochloric acid (500 mL). Separate the organic layer and extract with 2 N sodium hydroxide (400 mL). Make the aqueous layer slightly acidic (pH ˜5-6) by dropwise addition of 5 N hydrochloric acid and collect the resulting white precipitate by filtration. Dry the precipitate overnight under vacuum to provide 2-fluoro-5-iodophenylboronic acid as a white solid, which is used directly without further purification (39g, 98%). Stir for another 30 min warm the reaction to 40° C. Partition the reaction mixture between diethyl ether (500 mL) add 1 N hydrochloric acid (500 mL) Separate the organic layer extract with 2 N sodium hydroxide (400 mL) by dropwise addition of 5 N hydrochloric acid collect the resulting white precipitate by filtration Dry the precipitate overnight under vacuum