tributyl borate

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

Procedure: To a suspension of sodium hydride (130 mg, 5.41 mmol) in anhydrous tetrahydrofuran (20 mL) was added 6-bromoindole (973 mg, 4.96 mmol) (prepared according to W. A. Ayer et al., Tetrahedron 84(14):2919-2924 (1992)) at 0° C. After 15 min. of stirring at 0° C., the reaction was cooled to −78° C., and tert-butyllithium (10.2 mmol, 1.7 M in hexane) (Aldrich) was added dropwise (a white precipitate immediately formed). After 10 min. tri-n-butylborate (2.75 mL, 10.2 mmol) (Aldrich) was added dropwise. The reaction was allowed to warm to room temperature slowly, then the suspension was poured into an ice cold solution of 1N HCl. The organic phase was separated, and the aqueous phase was washed with ether. The combined organic extracts were extracted with 1N NaOH (3×25 mL), and the combined alkaline extracts were acidified to pH 1 with 1N HCl. The product was then extracted with ether, and the combined ether layers were dried over magnesium sulfate and concentrated in vacuo to yield a brownish solid. The product was recrystallized from boiling water to yield 412 mg (50%) white crystals. prepared at 0° C the reaction was cooled to −78° C. immediately formed) to warm to room temperature slowly The organic phase was separated the aqueous phase was washed with ether The combined organic extracts were extracted with 1N NaOH (3×25 mL) The product was then extracted with ether the combined ether layers were dried over magnesium sulfate concentrated in vacuo to yield a brownish solid The product was recrystallized

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

Procedure: To a suspension of sodium hydride (130 mg, 5.41 mmol) in anhydrous tetrahydrofuran (20 mL) was added 4-bromoindole (973 mg, 4.96 mmol) (see Kosuge et al. supra) at 0° C. After 15 min. of stirring at 0° C., the reaction was cooled to −78° C., and tert-butyllithium (10.2 mmol, 1.7 M in hexane) (Aldrich) was added dropwise (a white precipitate immediately formed). After 10 min. tri-n-butylborate (2.75 mL, 10.2 mmol) (Aldrich) was added dropwise. The reaction was allowed to slowly warm to room temperature, then the suspension was poured into an ice cold solution of 1N HCl. The organic phase was separated, and the aqueous phase was washed with ether. The combined organic extracts were extracted with 1N NaOH (3×25 mL), and the combined alkaline extracts were acidified to pH 1 with 1N HCl. The product was then extracted with ether, and the combined ether layers were dried over magnesium sulfate and concentrated in vacuo to yield a brownish solid. The product was recrystallized from boiling water to yield 367 mg (46%) white crystals. the reaction was cooled to −78° C. immediately formed) to slowly warm to room temperature The organic phase was separated the aqueous phase was washed with ether The combined organic extracts were extracted with 1N NaOH (3×25 mL) The product was then extracted with ether the combined ether layers were dried over magnesium sulfate concentrated in vacuo to yield a brownish solid The product was recrystallized

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

Procedure: To a suspension of sodium hydride (122 mg, 5.1 mmol) in anhydrous tetrahydrofuran (20 mL) was added 5-bromoindole (1.0 g, 5.1 mmol) (Aldrich) at 0° C. After 15 min. of stirring at 0° C., the reaction was cooled to −78° C., and tert-butyllithium (10.2 mmol, 1.7M in hexane) (Aldrich) was added dropwise (a white precipitate immediately formed). After 10 min. tri-n-butylborate (2.75 mL, 10.2 mmol) was added dropwise. The reaction was allowed to slowly warm to room temperature, then the suspension was poured into an ice cold solution of 1N HCl. The organic phase was separated, and the aqueous phase was washed with ether. The combined organic extracts were extracted with 1N NaOH (3×25 mL), and the combined alkaline extracts were acidified to pH 1 with 1N HCl. The product was then extracted with ether, and the combined ether layers were dried over magnesium sulfate and concentrated in vacuo to yield a brownish solid. The product was recrystallized from boiling water to yield 450 mg (55%) white crystals (mp >290° C.). the reaction was cooled to −78° C. immediately formed) to slowly warm to room temperature The organic phase was separated the aqueous phase was washed with ether The combined organic extracts were extracted with 1N NaOH (3×25 mL) The product was then extracted with ether the combined ether layers were dried over magnesium sulfate concentrated in vacuo to yield a brownish solid The product was recrystallized

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

Procedure: To a solution of 4-iodotoluene (35 g, 160.5 mmol) in diethyl ether (400 mL) was added n-butyllithium (2 M in pentane, 88.3 mL, 176.6 mmol) at 0° C. After stirring at 0° C. for another 15 min the solution was cooled to -60° C. and tributylborate (60.6 mL, 224.7 mmol) was added. The cooling bath was removed and the reaction allowed to heat up to room temperature. The solution was acidified with hydrochloric acid (2 N, 280 mL) and the organic phase separated off. The aqueous phase was extracted with diethyl ether 2×125 mL). The combined organic phases were extracted with sodium hydroxide (1 N, 5×50 mL). The combined aqueous extracts were acidified to give 18.6 g of the desired material. was cooled to -60° C. The cooling bath was removed to heat up to room temperature the organic phase separated off The aqueous phase was extracted with diethyl ether 2×125 mL) The combined organic phases were extracted with sodium hydroxide (1 N, 5×50 mL)

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

Procedure: A solution of 3,4-methylenedioxybromobenzene (2.00 g, 9.95 mmol) in anhydrous THF (20 ml) was added dropwise to magnesium turnings(254 mg, 10.45 mmol) and stirred for 1 h. After the reaction completed, the reaction mixture was cooled to −78° C., and a solution of tributyl borate (3.22 ml, 11.94 mmol) in anhydrous THF (30 ml) was added dropwise and stirred for 15 min at the same temperature. Cooling bath was removed and the reaction mixture was allowed to warm to ambient temperature and stirred for another 15 min. Ice water was added and the mixture was acidified with hydrochloric acid and extracted twice with ether. A combined organic layers were washed with brine and dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was air-dried to give 3,4-methylenedioxyphenyl boric acid (986 mg, 60%) as white crystals. stirred for 15 min at the same temperature Cooling bath was removed to warm to ambient temperature stirred for another 15 min Ice water was added extracted twice with ether A combined organic layers were washed with brine dried over magnesium sulfate the solvent was removed under reduced pressure The residue was air-dried

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

Procedure: A −78° C. solution of Example 68B (3.35 g, 15 mmol) diethyl ether (100 mL) was treated dropwise with 2.5 M n-butyllithium (7.2 mL, 18 mmol), stirred for 2 hours at −78° C., treated with tributyl borate (4.14 g, 18 mmol), stirred at −78° C. for one hour and warmed to room temperature over 2 hours. The solution was treated with pinacol (2.30 g, 19.5 mmol) and acetic acid (0.9 g, 15 mmol), stirred overnight, and filtered through diatomaceous earth (Celite®). The pad was washed with diethyl ether several times and the filtrate was concentrated to a volume of 50 mL. The mixture was diluted with ethyl acetate, washed with water and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with 25:1 hexanes/ethyl acetate to provide 2.34 g (70%) of the desired product. MS (DCI) m/e 224 (M+H)+; 1H NMR (300 MHz, CDCl3,) δ 8.24 (d, J=5.1 Hz, 1H), 7.50 (dd, J=4.8, 2.7 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 1.36 (s, 12H). stirred at −78° C. for one hour warmed to room temperature over 2 hours stirred overnight filtered through diatomaceous earth (Celite®) The pad was washed with diethyl ether several times the filtrate was concentrated to a volume of 50 mL The mixture was diluted with ethyl acetate washed with water and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel eluting with 25:1 hexanes/ethyl acetate

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

Procedure: A −78° C. solution of Example 68B (3.35 g, 15 mmol) diethyl ether (100 mL) was treated dropwise with 2.5 M n-butyllithium (7.2 mL, 18 mmol), stirred for 2 hours at −78° C., treated with tributyl borate (4.14 g, 18 mmol), stirred at −78° C. for one hour and warmed to room temperature over 2 hours. The solution was treated with pinacol (2.30 g, 19.5 mmol) and acetic acid (0.9 g, 15 mmol), stirred overnight, and filtered through diatomaceous earth (Celite®). The pad was washed with diethyl ether several times and the filtrate was concentrated to a volume of 50 mL. The mixture was diluted with ethyl acetate, washed with water and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with 25:1 hexanes/ethyl acetate to provide 2.34 g (70%) of the desired product. MS (DCI) m/e 224 (M+H)+; 1H NMR (300 MHz, CDCl3,) δ 8.24 (d, J=5.1 Hz, 1H), 7.50 (dd, J=4.8, 2.7 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 1.36 (s, 12H). stirred at −78° C. for one hour warmed to room temperature over 2 hours stirred overnight filtered through diatomaceous earth (Celite®) The pad was washed with diethyl ether several times the filtrate was concentrated to a volume of 50 mL The mixture was diluted with ethyl acetate washed with water and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel eluting with 25:1 hexanes/ethyl acetate

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

Procedure: A solution of 4-bromo-5-isopropyl-1H-indazole (116 g, 6.9 mmol) in Et2O (4 mL) is added slowly to a suspension of KH (1.0 g of 30% dispersion in mineral oil, 7.7 mmol) in Et2O (20 mL) at 0° C. and the mixture is stirred for 20 minutes. After cooling to −78° C., t-BuLi (8.9 mL of 1.7 M in Hex, 15 mmol) is added and the resulting mixture is stirred for 40 minutes at −78° C. To this is added B(On-Bu)3 (5.6 mL, 21 mmol) and the mixture is stirred for 24 hours at room temperature. The reaction mixture is quenched with 1N H3PO4 and extracted with Et2O— The combined Et2O layers are back-extracted with 1N NaOH (3×10 mL). The combined NaOH extracts are acidified with 1N H3PO4 and extracted with EtOAc. The EtOAc extracts are washed with saturated brine, dried (MgSO4), and concentrated to yield 5-isopropyl-1H-indazole-4-boronic acid. 1H NMR (CDCl3) 7.85 (s, 1H), 7.42 (d, 1H), 7.37 (d, 1H), 3.6 (br s, 2H), 2.88 (m, 1H), 1.32 (d, 6H). the resulting mixture is stirred for 40 minutes at −78° C the mixture is stirred for 24 hours at room temperature The reaction mixture is quenched with 1N H3PO4 extracted with Et2O— The combined Et2O layers are back-extracted with 1N NaOH (3×10 mL) extracted with EtOAc The EtOAc extracts are washed with saturated brine dried (MgSO4) concentrated

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

Procedure: A solution of 4-bromo-5-isopropyl-1H-indazole (116 g, 6.9 mmol) in Et2O (4 mL) is added slowly to a suspension of KH (1.0 g of 30% dispersion in mineral oil, 7.7 mmol) in Et2O (20 mL) at 0° C. and the mixture is stirred for 20 minutes. After cooling to −78° C., t-BuLi (8.9 mL of 1.7 M in Hex, 15 mmol) is added and the resulting mixture is stirred for 40 minutes at −78° C. To this is added B(On-Bu)3 (5.6 mL, 21 mmol) and the mixture is stirred for 24 hours at room temperature. The reaction mixture is quenched with 1N H3PO4 and extracted with Et2O— The combined Et2O layers are back-extracted with 1N NaOH (3×10 mL). The combined NaOH extracts are acidified with 1N H3PO4 and extracted with EtOAc. The EtOAc extracts are washed with saturated brine, dried (MgSO4), and concentrated to yield 5-isopropyl-1H-indazole-4-boronic acid. 1H NMR (CDCl3) 7.85 (s, 1H), 7.42 (d, 1H), 7.37 (d, 1H), 3.6 (br s, 2H), 2.88 (m, 1H), 1.32 (d, 6H). the resulting mixture is stirred for 40 minutes at −78° C the mixture is stirred for 24 hours at room temperature The reaction mixture is quenched with 1N H3PO4 extracted with Et2O— The combined Et2O layers are back-extracted with 1N NaOH (3×10 mL) extracted with EtOAc The EtOAc extracts are washed with saturated brine dried (MgSO4) concentrated