4-(2-(diMethylaMino)ethoxy)-3-fluorophenylboronic acid synthesis

Yield:944279-23-6 73%

Reaction Conditions:

Stage #1: [2-(4-bromo-2-fluoro-phenoxy)-ethyl]-dimethyl-aminewith iodine;magnesium in tetrahydrofuran; for 1 h;Heating / reflux;
Stage #2: with Trimethyl borate in tetrahydrofuran at -78;
Stage #3: with hydrogenchloride in tetrahydrofuran;water; for 0.5 h;

Steps:

20.2

To a solution of [2-(4-Bromo-2-fluoro-phenoxy)-ethyl]-dimethyl-amine from stepl (4.Ig) in THF (40ml) was added a small crystal of iodine and then Mg (570mg, 1.5eq) portion-wise. After addition, the mixture was heated to reflux for Ih. The grey mixture was cooled to -78° trimethylborate (1.2eq, 2.1ml) added drop-wise and allowed to warm overnight. IN HCl (aq, 60ml) was added and stirred for 30 min before being extracted into ether (2x50ml). The combined organic phases were dried and concentrated and the resulting solid triturated with acetone / ether, isolated by filtration and dried to give the title compound as a brown solid (2.6g, 73%). The product was used crude without further purification.

References:

WO2007/80401,2007,A1 Location in patent:Page/Page column 48