N,N,N',N'-Tetramethylethylenediamine → {4-[(tert-Butoxycarbonyl)amino]pyridin-3-yl}boronic acid

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Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, a solution of n-butyllithium in hexane (100 mL of 2.5 M, 250 mmol) was added over 20 minutes to a stirred solution of tert-butyl pyridin-4-ylcarbamate (19.4 g, 100 mmol) and N,N,N′,N′-tetramethylethylenediamine (TMEDA) (31.4 g, 270 mmol) in tetrahydrofuran (THF) (500 mL) at −78° C. tert-Butyl pyridin-4-ylcarbamate is available from a literature procedure (Spivey, A. C. et al. J. Org. Chem. 1999, 64, 9430-9443). A white solid appeared and the mixture was stirred for 10 minutes at −78° C., was transferred to a salt bath, and allowed to warm slowly to −4° C. over about two hours before cooling to −78° C. again. Trimethyl borate (39.5 g, 380 mmol) was added over 15 minutes. The solution was warmed to 0° C. and poured into saturated aqueous ammonium chloride (500 mL). The mixture was stirred for 2 minutes. After standing at room temperature overnight, the mixture was partitioned between diethyl ether and brine. The organic layer was separated and washed with brine and then diluted to a volume of 3 liters with the addition of diethyl ether. A white solid formed in the organic layer and was isolated by filtration. The solid was washed sequentially with diethyl ether, water, and diethyl ether, then was dried to provide 17.1 g of 4-[(tert-butoxycarbonyl)amino]pyridin-3-ylboronic acid as a white solid.

Provenance & Evidence