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Under a nitrogen atmosphere, a solution of tert-butyl iV-(2-ρyridyl)carbamate (15.71 g, 80.9 mmol) and iV.ΛζN'.N'-tetramethylethylenediamine (TMEDA) (25.3 g, 218 mmol) in THF (400 mL) was cooled to -78 0C. M-Butyllithium (81 mL of a 2.5 M solution in hexanes) was added dropwise over a period of 20 minutes. The solution was stirred for ten minutes, and then the addition funnel was rinsed with additional THF (20 mL). The solution was warmed to -6 0C, stirred for two hours, and cooled again to -78 0C. Triisopropyl borate (57.7 g, 307 mmol) was added over a period often minutes. The resulting solution was warmed to 00C and then poured into saturated aqueous ammonium chloride (500 mL). A yellow solid formed and was stirred with diethyl ether (300 mL), isolated by filtration, washed with diethyl ether and water, and air-dried overnight to provide 2-ført-butoxycarbonylamino-3-pyridylboronic acid as a yellow solid. |
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Manufacturing Example 1-7-22-N-butoxycarbonyl-3-pyridineboronic acid; A tetrahydrofuran solution (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 1-7-1 and N,N,N',N'-tetramethylethylenediamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added dropwise over a period of 1 hour, which was stirred for 10 minutes. This mixture was warmed to a temperature between -10 C. and -6 C., which was stirred for 2 hours at that temperature. The solution was again cooled to -70 C., and triisobutyl borate (58 g) was added dropwise over a period of 1 hour. This mixture was warmed to 0 C., and then a saturated ammonium chloride aqueous solution was added thereto. Ether was added to the yellow solid thus produced, which was stirred, and the solid was then collected by filtration and washed with ether and water. This solid was dried under a reduced pressure, so as to obtain the title compound (14 g).1H-NMR spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-8.13 (2H, m). |
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A solution of pyridin-2-yl-carbamic acid tert-butyl ester described in Preparation Example 4-1-1 (16 g) and N,N,N',N'-tetramethyl ethylenediamine (25 g) in tetrahydrofuran (400 mL) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added thereto dropwise over one hour, and stirred for 10 minutes. This mixture was heated to between -10 C. and -6 C., and stirred at this temperature for two hours. Again, this solution was cooled to 70 C., and triisobutyl borate (58 g) was added thereto dropwise over one hour. This mixture was heated to 0 C., then, a saturated aqueous ammonium chloride was added thereto. To the produced yellow solid was added ether, and stirred, and then, a solid was recovered by filtration and washed with ether and water. This solid was in vacuo to obtain the title compound (14 g). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m). |
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