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

Temperature

-78 °C

A 2.5 M solution of n-butyl lithium in hexane (100 mL, 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 (31.4 g, 270 mmol) in 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., then was allowed to warm slowly to −4° C. before cooling to −78° C. again. Trimethyl borate (39.5 g, 380 mmol) was added over 15 minutes. The solution was allowed to warm to 0° C., then was poured into saturated aqueous ammonium chloride (500 mL). The mixture was stirred for 2 minutes. After standing at ambient temperature overnight, the mixture was partitioned between diethyl ether and brine. The organic layer was separated and washed with brine. 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.

1. temperatureto warm slowly to −4° C.
2. temperaturebefore cooling to −78° C. again
3. temperatureto warm to 0° C.
4. stirringThe mixture was stirred for 2 minutes
5. waitAfter standing at ambient temperature overnight
6. customthe mixture was partitioned between diethyl ether and brine
7. customThe organic layer was separated
8. washwashed with brine
9. customA white solid formed in the organic layer
10. customwas isolated by filtration
11. washThe solid was washed sequentially with diethyl ether, water, and diethyl ether
12. customwas dried

ORD record

ord-7c29bf990b974127b8851b83afcf93b8

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07544697B2