3,4-DIFLUORO-N-HYDROXY-BENZAMIDINE synthesis

Yield:500024-74-8 1.24 g

Reaction Conditions:

with hydroxylamine hydrochloride;triethylamine in ethanol;water at 75; for 2 h;

Steps:

24.1 Step 1: Preparation of 3, 4-difluoro-N-hydroxybenzimidamide.

To a stirred solution of 3,4-difluorobenzonitrile (1 .0 g, 7.19 mmol) in ethanol (20 mL) were addedhydroxylamine hydrochloride (999 mg, 14.4 mmol), triethylamine (1.46 g, 14.4 mmol, 1.99 mL), and water(2 mL). The mixture was heated at 75 °C for 2 h. After cooling to 20 00, water (20 mL) was added to the solution. The mixture was extracted with dichloromethane (30 mL x 4). The combined organic layers were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous sodium sulfate, then filtered, and concentrated in vacuo to give 3,4-difluoro-N-hydroxybenzimidamide (1 .24 g) as a white solid. This was used directly without further purification. 1H NMR (400 MHz, DMSO-d6) O 9.79 (s, 1H), 7.68 (ddd, J2.0, 8.0, 12.2 Hz, 1H), 7.55 (br. s., 1H), 7.50-7.39(m, 1H), 5.92 (br. 5., 2H).

References:

WO2018/81167,2018,A1 Location in patent:Page/Page column 118; 119