1H-Indole-7-carbonitrile, 6-fluoro- synthesis

Yield:1201148-85-7 89%

Reaction Conditions:

with tetrakis-(triphenylphosphine)-palladium in N,N-dimethyl-formamide at 140; for 4 h;Inert atmosphere;

Steps:

A.1 Step 1:

To a degassed solution of 7-bromo-6-fluoro-1H-indole (700 mg, 3.27 mmol) in N,N-dimethylformamide (8 mL ) were added zinc cyanide (1152 mg, 9.81 mmol) and palladium(0)tetrakis(triphenylphosphine) (378 mg, 0.32 mmol) under nitrogen atmosphere. The resulting solution was stirred at 140 °C for 4 h. The solids were filtered off. The filtrate was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash column chromatography with 0-20% ethyl acetate in petroleum ether to afford 6-fluoro-1 H-indole-7-carbonitrile (470 mg, 89%) as a white solid. MS m/z 161.0 [M+1]⁺.

References:

WO2022/20342,2022,A1 Location in patent:Page/Page column 40; 93