2-ETHYL-6-METHYLPHENYLBORONIC ACID synthesis

Yield:953075-89-3 81%

Reaction Conditions:

Stage #1: 2-methyl-6-ethylphenyl iodidewith n-butyllithium in tetrahydrofuran;n-heptane at -73 - -70; for 2.5 h;Inert atmosphere;
Stage #2: in tetrahydrofuran;hexane at -72 - 20; for 21 h;Inert atmosphere;
Stage #3: with hydrogenchloride;water in tetrahydrofuran;hexane at 20;Inert atmosphere;

Steps:

21.a Synthesis of (2-ethyl-6-methyl-phenyl)boronic acid

45.9 ml (115 mmol) of 2.5M n-butyl lithium solution in hexane is slowly treated at -73°C with24.0 g (23.5 mmol) of 1-ethyl-2-iodotoluene in 200 ml of THF under argon atmosphere,letting the temperature not rise above -70°C. Addition is completed after 90 minutes, and stirring continued at -73°C during one hour, giving a white suspension. 15.9 ml (142 mmol) of trimethylborate are slowly added during one hour at -73°C, letting the temperature not rise above -70°C. The temperature is let raising to room temperature during two hours (aspect: clear and colorless solution), and stirring continued for 18 hours. The slightly turbidsolution is slowly treated with water by intermittent cooling with an ice-bath, followed by the addition of 30 ml of 10% aqeuous hydrochloric acid solution at room temperature. The organic solvents are distilled off at a bath-temperature of 80°C. Heptane is added and the mixture stirred at 0°C during one hour. The resulting suspension is filtered and the solid washed with a small amount of ice-cold water and heptane, followed by drying undervacuum, giving the title product as an off-white solid (yield: 12.9 g (81%)).1HNMR (400 MHz, CDCI3): = 1.26 (t, 3 H), 2.38 (s, 3 H), 2.67 (q, 2 H), 5.03 (s, 2 H), 7.01(d, I H), 7.05 (d, I H), 7.05 (d, I H), 7.21 (d, I H).

References:

WO2015/14835,2015,A1 Location in patent:Page/Page column 176; 177