HEXADECYLBORONIC ACID synthesis

Yield:-

Reaction Conditions:

Stage #1: hexadecanyl bromidewith magnesium;iodine in diethyl ether; for 3 h;Inert atmosphere;
Stage #2: with Trimethyl borate in diethyl ether at -78 - 20;Inert atmosphere;
Stage #3: with hydrogenchloride;water in diethyl ether at 20;

Steps:

II

II. Hexadecylboronic Acid; Magnesium turnings (2.55 g) were added to a dry 3-necked round bottom flask equipped with a reflux condenser that had been flushed with argon. Dry ether (4.5 mL) was added followed by one crystal of iodine. 1-Bromohexadecane (10 mL, 10.0 g, 32.75 mmol) was dissolved into 11 mL ether and over one hour to the magnesium under ether. After complete addition of the bromide, the solution was allowed to stir for 2 hours without external heating.A dry 250 mL round bottom flask cooled to -78° C. equipped with a pressure equalizing addition funnel was flushed with argon and dry ether (80 mL) was added to the flask followed by addition of trimethylborate (3.75 mL, 33 mmol). Compound b was then added dropwise over one hour. The solution was stirred for an additional hour before removing the cold bath and allowing the reaction to warm to room temperature. 10% HCl (50 mL) was then added dropwise to the reaction flask at room temperature. After 15 minutes of additional stirring, the biphasic solution was extracted into ether. The ethereal solutions were dried over MgSO₄ and the ether removed under reduced pressure. The resulting white solid was purified as follows by adding water (90° C.) to dissolve the products, the solution was then cooled to 4° C. to allow the boronic acid to precipitate as a white solid. This was filtered, the solid collected, and then washed with hexanes (60° C.). The flask was placed in the freezer for 1 hour. The precipitate was filtered, collected, and dried under vacuum to provide Inhibitor B.

References:

US2009/209492,2009,A1 Location in patent:Page/Page column 9