tripropyl borate

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

Procedure: 1,2-Difluorobenzene (40 g, 0.35 mol) and dry tetrahydrofurane (400 ml) were placed in 1 L flask equipped with mechanical stirrer, nitrogen inlet and outlet, pressure-equilibrated dropping funnel and thermometer. The reaction flask was flushed with nitrogen and minor flow was held during whole reaction time. The mixture was cooled down to −78° C. with dry ice/acetone bath and 2.5 mol/L hexane solution of n-butyllithium (140 ml; 0.35 mol) was added dropwise, keeping the reaction temperature below −70° C. After addition of all butyllithium solution the mixture was stirred at −78° C. for 2 h and then tripropylborate (66 g, 0.35 mol) was added dropwise keeping the reaction temperature below −70° C. After addition of tripropyl borate the cooling bath was removed and the reaction mixture continuously stirred to reach the room temperature then the solvents were evaporated. The thick liquid residue was acidified and then propanol was evaporated and the remaining solid was filtered off, washed out with hexane and recrystalized from water. The white crystalline product 47 g was obtained, with 85% of theor. yield. equipped with mechanical stirrer, nitrogen inlet and outlet The reaction flask was flushed with nitrogen and minor flow the reaction temperature below −70° C the reaction temperature below −70° C was removed the reaction mixture continuously stirred the room temperature the solvents were evaporated propanol was evaporated the remaining solid was filtered off washed out with hexane recrystalized from water

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

Procedure: 1,2-Difluorobenzene (40 g, 0.35 mol) and dry tetrahydrofurane (400 ml) were placed in 1 L flask equipped with mechanical stirrer, nitrogen inlet and outlet, pressure-equilibrated dropping funnel and thermometer. The reaction flask was flushed with nitrogen and minor flow was held during whole reaction time. The mixture was cooled down to −78° C. with dry ice/acetone bath and 2.5 mol/L hexane solution of n-butyllithium (140 ml; 0.35 mol) was added dropwise, keeping the reaction temperature below −70° C. After addition of all butyllithium solution the mixture was stirred at −78° C. for 2 h and then tripropylborate (66 g, 0.35 mol) was added dropwise keeping the reaction temperature below −70° C. After addition of tripropyl borate the cooling bath was removed and the reaction mixture continuously stirred to reach the room temperature then the solvents were evaporated. The thick liquid residue was acidified and then propanol was evaporated and the remaining solid was filtered off, washed out with hexane and recrystalized from water. The white crystalline product 47 g was obtained, with 85% of theor. yield. equipped with mechanical stirrer, nitrogen inlet and outlet The reaction flask was flushed with nitrogen and minor flow the reaction temperature below −70° C the reaction temperature below −70° C was removed the reaction mixture continuously stirred the room temperature the solvents were evaporated propanol was evaporated the remaining solid was filtered off washed out with hexane recrystalized from water

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

Procedure: 20 g (76 mmol) of 3-Benzyloxybromobenzene was dissolved in 200 mL of anhydrous THF and cooled to -78° C. under a nitrogen atmosphere. To the stirring solution, 90 mL of 1.6 M n-BuLi (83.6 mmol) was slowly added. After several minutes, 33.6 mL (83.6 mmol) tripropylborate was added and the reaction was allowed to slowly warm to ambient temperature over the next four hours. The reaction was quenched with the addition of 400 mL of 1N HCl. The reaction mixture was extracted three times with EtOAc. The EtOAc solution was washed twice with brine, dried with Na2SO4, and evaporated to dryness. The final product was crystallized from EtOAc-hexane. This yielded 10 g of the title compound as a white solid. After several minutes to slowly warm to ambient temperature over the next four hours The reaction was quenched with the addition of 400 mL of 1N HCl The reaction mixture was extracted three times with EtOAc The EtOAc solution was washed twice with brine dried with Na2SO4 evaporated to dryness The final product was crystallized from EtOAc-hexane

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

Procedure: 20 g (76 mmol) of 3-Benzyloxybromobenzene was dissolved in 200 mL of anhydrous THF and cooled to -78° C. under a nitrogen atmosphere. To the stirring solution, 90 mL of 1.6 M n-BuLi (83.6 mmol) was slowly added. After several minutes, 33.6 mL (83.6 mmol) tripropylborate was added and the reaction was allowed to slowly warm to ambient temperature over the next four hours. The reaction was quenched with the addition of 400 mL of 1N HCl. The reaction mixture was extracted three times with EtOAc. The EtOAc solution was washed twice with brine, dried with Na2SO4, and evaporated to dryness. The final product was crystallized from EtOAc-hexane. This yielded 10 g of the title compound as a white solid. After several minutes to slowly warm to ambient temperature over the next four hours The reaction was quenched with the addition of 400 mL of 1N HCl The reaction mixture was extracted three times with EtOAc The EtOAc solution was washed twice with brine dried with Na2SO4 evaporated to dryness The final product was crystallized from EtOAc-hexane

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

Procedure: 1,2-Difluorobenzene (40 g, 0.35 mol) and dry tetrahydrofurane (400 ml) were placed in 1 L flask equipped with mechanical stirrer, nitrogen inlet and outlet, pressure-equilibrated dropping funnel and thermometer. The reaction flask was flushed with nitrogen and minor flow was held during whole reaction time. The mixture was cooled down to −78° C. with dry ice/acetone bath and 2.5 mol/L hexane solution of n-butyllithium (140 ml; 0.35 mol) was added dropwise, keeping the reaction temperature below −70° C. After addition of all butyllithium solution the mixture was stirred at −78° C. for 2 h and then tripropylborate (66 g, 0.35 mol) was added dropwise keeping the reaction temperature below −70° C. After addition of tripropyl borate the cooling bath was removed and the reaction mixture continuously stirred to reach the room temperature then the solvents were evaporated. The thick liquid residue was acidified and then propanol was evaporated and the remaining solid was filtered off, washed out with hexane and recrystalized from water. The white crystalline product 47 g was obtained, with 85% of theor. yield. equipped with mechanical stirrer, nitrogen inlet and outlet The reaction flask was flushed with nitrogen and minor flow the reaction temperature below −70° C the reaction temperature below −70° C was removed the reaction mixture continuously stirred the room temperature the solvents were evaporated propanol was evaporated the remaining solid was filtered off washed out with hexane recrystalized from water

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

Procedure: Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 6-bromo-3-ethyl-1-phenyl-1H-indazole (2 g, 6.64 mmol, 1.00 equiv) in tetrahydrofuran (20 mL). To the resulting mixture was then added a solution of n-BuLi (4 mL, 1.40 equiv) in tetrahydrofuran (5 mL) dropwise with stirring at −78° C. in 5 min. The resulting mixture was stirred for 30 min at the temperature. To the resulting mixture was then added a solution of tripropyl borate (1.49 g, 7.93 mmol, 1.20 equiv) in tetrahydrofuran (5 mL) dropwise with stirring at −78° C. in 5 min. The resulting solution was stirred for 1 h at −78° C. in a liquid nitrogen bath. The reaction was then quenched by the addition of water (30 mL). The resulting solution was extracted with ethyl acetate (2×50 mL), the organic layers combined and dried over anhydrous sodium sulfate, then concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5) to yield 3-ethyl-1-phenyl-1H-indazol-6-ylboronic acid as a white solid. Into a 250-mL 3-necked round-bottom flask purged maintained with an inert atmosphere of nitrogen The resulting mixture was stirred for 30 min at the temperature with stirring at −78° C. in 5 min The resulting solution was stirred for 1 h at −78° C. in a liquid nitrogen bath The reaction was then quenched by the addition of water (30 mL) The resulting solution was extracted with ethyl acetate (2×50 mL) dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: n-Butyllithium (2.5M solution in hexane, 9.6 mL, 24 mmol) was added to a mixture of diisopropylamine (3.4 mL, 24 mmol) in THF (5.00 mL, 61 mmol) at 0° C. and the resulting pale yellow solution was stirred at the same temperature for 30 min and then cooled down to −78° C. A suspension of 2-fluoro-5-methylpyridine (Aldrich, St. Louis, Mo.) (2.22 g, mmol) in THF (5.00 mL, not complete dissolved) was slowly added. The resulting bright yellow solution was stirred at −78° C. for 1 h, treated with a solution of tri-1-propylborate (6.9 mL, 30 mmol) in THF (10.00 mL) and then allowed to warm up to room temperature. The yellow suspension was quenched with 1 N NaOH until basic (pH about 10) and the organic layer was separated. The aqueous layer was collected and carefully acidified with 6N aqueous HCl until slightly acidic, and then extracted with EtOAc(×3). The combined organic layers were dried (Na2SO4), filtered and concentrated. The resulting white solid was washed with ether to give 2-fluoro-5-methylpyridin-3-ylboronic acid (2.9196 g, 94% yield) as a white solid. LCMS (API-ES) m/z 156 (M+H)+. not complete dissolved) was slowly added The resulting bright yellow solution was stirred at −78° C. for 1 h to warm up to room temperature The yellow suspension was quenched with 1 N NaOH until basic (pH about 10) the organic layer was separated The aqueous layer was collected then extracted with EtOAc(×3) The combined organic layers were dried (Na2SO4) filtered concentrated The resulting white solid was washed with ether

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

Procedure: 20 g (76 mmol) of 3-Benzyloxybromobenzene was dissolved in 200 mL of anhydrous THF and cooled to -78° C. under a nitrogen atmosphere. To the stirring solution, 90 mL of 1.6 M n-BuLi (83.6 mmol) was slowly added. After several minutes, 33.6 mL (83.6 mmol) tripropylborate was added and the reaction was allowed to slowly warm to ambient temperature over the next four hours. The reaction was quenched with the addition of 400 mL of 1N HCl. The reaction mixture was extracted three times with EtOAc. The EtOAc solution was washed twice with brine, dried with Na2SO4, and evaporated to dryness. The final product was crystallized from EtOAc-hexane. This yielded 10 g of the title compound as a white solid. After several minutes to slowly warm to ambient temperature over the next four hours The reaction was quenched with the addition of 400 mL of 1N HCl The reaction mixture was extracted three times with EtOAc The EtOAc solution was washed twice with brine dried with Na2SO4 evaporated to dryness The final product was crystallized from EtOAc-hexane

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

Procedure: 1,2-Difluorobenzene (40 g, 0.35 mol) and dry tetrahydrofurane (400 ml) were placed in 1 L flask equipped with mechanical stirrer, nitrogen inlet and outlet, pressure-equilibrated dropping funnel and thermometer. The reaction flask was flushed with nitrogen and minor flow was held during whole reaction time. The mixture was cooled down to −78° C. with dry ice/acetone bath and 2.5 mol/L hexane solution of n-butyllithium (140 ml; 0.35 mol) was added dropwise, keeping the reaction temperature below −70° C. After addition of all butyllithium solution the mixture was stirred at −78° C. for 2 h and then tripropylborate (66 g, 0.35 mol) was added dropwise keeping the reaction temperature below −70° C. After addition of tripropyl borate the cooling bath was removed and the reaction mixture continuously stirred to reach the room temperature then the solvents were evaporated. The thick liquid residue was acidified and then propanol was evaporated and the remaining solid was filtered off, washed out with hexane and recrystalized from water. The white crystalline product 47 g was obtained, with 85% of theor. yield. equipped with mechanical stirrer, nitrogen inlet and outlet The reaction flask was flushed with nitrogen and minor flow the reaction temperature below −70° C the reaction temperature below −70° C was removed the reaction mixture continuously stirred the room temperature the solvents were evaporated propanol was evaporated the remaining solid was filtered off washed out with hexane recrystalized from water