(2-fluoro-4-methylphenyl)boronic acid

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:

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:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 mL three-necked round-bottomed flask equipped with septum and N2 inlet were added 10.0 g (52.9 mmol) 4-bromo-3-fluorotoluene and 100 mL dry tetrahydrofuran. The solution was cooled to −70° C., and 25.4 mL (63.5 mmol) of a 2.5 M solution of butyl lithium in hexane was added slowly so the temperature did not exceed −60° C. The clear solution was stirred at −70° C. for 1 hour, then treated with 10.8 mL (63.5 mmol) triethylborate. The reaction was stirred for 2 hours at −70° C., then warmed to room temperature and stirred for 16 hours. The reaction was quenched with saturated aqueous ammonium chloride solution, adjusted to pH 1-2 with 1 N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was triturated with hexane to a white solid, 6.1 g (75%), as a mixture of monoaryl and diaryl boronic acids. did not exceed −60° C The reaction was stirred for 2 hours at −70° C. warmed to room temperature stirred for 16 hours The reaction was quenched with saturated aqueous ammonium chloride solution extracted with ethyl acetate The organic layer was washed with brine dried over sodium sulfate evaporated The residue was triturated with hexane to a white solid, 6.1 g (75%), as a mixture of monoaryl and diaryl boronic acids

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

Procedure: To a 500 mL three-necked round-bottomed flask equipped with septum and N2 inlet were added 10.0 g (52.9 mmol) 4-bromo-3-fluorotoluene and 100 mL dry tetrahydrofuran. The solution was cooled to −70° C., and 25.4 mL (63.5 mmol) of a 2.5 M solution of butyl lithium in hexane was added slowly so the temperature did not exceed −60° C. The clear solution was stirred at −70° C. for 1 hour, then treated with 10.8 mL (63.5 mmol) triethylborate. The reaction was stirred for 2 hours at −70° C., then warmed to room temperature and stirred for 16 hours. The reaction was quenched with saturated aqueous ammonium chloride solution, adjusted to pH 1-2 with 1 N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was triturated with hexane to a white solid, 6.1 g (75%), as a mixture of monoaryl and diaryl boronic acids. did not exceed −60° C The reaction was stirred for 2 hours at −70° C. warmed to room temperature stirred for 16 hours The reaction was quenched with saturated aqueous ammonium chloride solution extracted with ethyl acetate The organic layer was washed with brine dried over sodium sulfate evaporated The residue was triturated with hexane to a white solid, 6.1 g (75%), as a mixture of monoaryl and diaryl boronic acids

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 3-bromo-5-iodo-benzoate (13 g) and 2-fluoro-4-methylphenylboronic acid (6 g) were dissolved in DMF (120 mL) at room temperature. The solution was then cooled down to 0° C. with ice bath. To this solution was added aq. sodium carbonate (6 g in 50 mL of water), Pd(dppf)Cl2 (3 g) and DMF (10 mL). After the addition, the reaction was warmed up slowly to room temperature. The reaction mixture was then stirred at room temperature for 4 hrs. Solvent was evaporated under reduced pressure. The residue was re-dissolved in EtOAc (200 mL) washed with HCl (1M) 3×200 mL), sat. NaHCO3 (3×100 mL), brine (3×100 mL) and water (3×100 mL). The organic layer was separated and concentrated. The crude product was then purified with column chromatography (silica gel, eluted with EtOAc/Hexane, 0 to 1%) to give pure compound. Note a second column can be done to further remove unwanted bis cross coupled by-product. After the addition the reaction was warmed up slowly to room temperature Solvent was evaporated under reduced pressure The residue was re-dissolved in EtOAc (200 mL) washed with HCl (1M) 3×200 mL), sat. NaHCO3 (3×100 mL), brine (3×100 mL) and water (3×100 mL) The organic layer was separated concentrated The crude product was then purified with column chromatography (silica gel, eluted with EtOAc/Hexane, 0 to 1%) to give pure compound