3-Cyano-4-fluoro-5-methoxyphenylboronic acid pinacol ester synthesis

Yield:-

Reaction Conditions:

4,4'-di-tert-butyl-2,2'-bipyridine in hexane at 25;Inert atmosphere;

Steps:

79
Intermediate 792-Fluoro-3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile; A flask containing 2-fluoro-3-methoxybenzonitrile (302 mg, 2.00 mmol), 4,4'-di-tert-butyl-2,2'-dipyridyl (8 mg, 0.03 mmol) and bis(pinacolato)diboron (254 mg, 1.0 mmol) was flushed with argon, and then charged with hexane (6 mL). The mixture was then stirred at 25° C. overnight. The reaction mixture was diluted with EtOAc and washed with brine. The organic phase was concentrated and the crude product was purified on a silica column (0-50% EtOAc/n-heptane) to give the title compound (362 mg with 73% purity according to HPLC): ¹H NMR (500 MHz, DMSO-d₆) δ ppm 7.63-7.55 (m, 2H), 3.93 (s, 3H), 1.31 (s, 12H); MS (EI) m/z 277 M⁺.

References:

ASTRAZENECA AB US2012/165347, 2012, A1 Location in patent:Page/Page column 41-42