Benzamide, N-(5-bromo-2-pyrazinyl)-2,6-difluoro- synthesis

Yield:1028700-78-8 85%

Reaction Conditions:

with triethylamine in dichloromethane at 20; for 15 h;Inert atmosphere;

Steps:

47

Preparation of N-(5-bromopyrazin-2-yl)-2,6-difluorobenzamide (17).; Under an atmosphere of argon, 2,6-difluorobenzoyl chloride (20.3 g, 115 mmol) was added to a stirred solution of 15 (10.0 g, 57.5 mmol) and triethylamine (24.0 mL, 17.4 g, 172 mmol) in dichloromethane (145 mL) at room temperature. The reaction was stirred for 15 h. The mixture was quenched with saturated sodium bicarbonate solution (100 mL) and extracted with dichloromethane (3×100 mL). The combined organic extracts were dried with sodium sulfate and concentrated under reduced pressure. The crude material was dissolved with tetrahydrofuran (200 mL), methanol (100 mL) and 2 M sodium hydroxide solution (75 mL). The mixture was stirred room temperature for 20 min then extracted with 1:1 ethyl acetate:hexane (3×300 mL), dried with brine (100 mL) then sodium sulfate and concentrated under reduced pressure. Flash chromatography (silica, 25% ethyl acetate in hexane) followed by crystallization from ethyl acetate in hexane provided 17 (15 g, 84%) as a crystalline solid: LRESIMS m/z 314.0 [M+H]⁺, calcd. for C₁₁H₇Br₁F₂N₃O₁ 314.0.

References:

US2011/263612,2011,A1 Location in patent:Page/Page column 161