2-bromo-5-(4-fluorophenyl)pyrazine synthesis

Yield:153295-35-3 57%

Reaction Conditions:

Stage #1: 2-5-dibromopyrazine;4-fluoroboronic acidwith sodium carbonate in ethanol;toluene; for 0.25 h;Inert atmosphere;
Stage #2: with tetrakis(triphenylphosphine) palladium⁽⁰⁾ at 40; for 1.25 h;Inert atmosphere;

Steps:

11.1 Step 1: 2-Bromo-5-(4-fluorophenyl)pyrazine

Step 1: 2-Bromo-5-(4-fluorophenyl)pyrazine To a solution of 2,5-dibromopyrazine (100 mg, 0.4 mmol) in toluene (6 mL) and ethanol (3 mL) was added (4-fluorophenyl)boronic acid (29 mg, 0.2 mmol) and 2M sodium carbonate solution (2.84 mL). The solution was purged with argon for 15 min, Pd(PPh₃)₄ (4 mg, 0.004 mmol) was added, and the reaction mixture was purged with argon for 15 min. The resulting mixture was heated to 40°C and stirred for 1 h. The reaction mixture was concentrated, diluted with water (20 mL), and extracted with ethyl acetate (2 x 100 mL). The combined extracts were washed with brine solution (10 mL), and dried over Na₂S0₄ and concentration in vacuo. The crude product was purified by flash chromatography (60-120μ, 5% ethyl acetate in hexane) to afford 2-bromo-5-(4-fluorophenyl)pyrazine as off-white solid (60 mg, 57% yield). 1H MR (400 MHz, DMSO-d₆): δ 9.08 (s, 1H), 8.88 (s, 1H), 8.18-8.15 (m, 2H), 7.37 (dd, 2H); LC-MS m/z calculated for [M+H]⁺ 252.97, found 253.0. -(5-(4-Fluorophenyl)pyrazin-2-yl)-l-(pyridin-4-yl)ethanol

References:

WO2013/49559,2013,A1 Location in patent:Page/Page column 59; 60