1-chloro-2-(difluoromethoxy)-4-nitrobenzene synthesis

Yield:40319-62-8 95%

Reaction Conditions:

Stage #1: 5-nitro-2-chlorophenol;sodium chlorodifluoroacetatewith potassium carbonate in water;N,N-dimethyl-formamide at 100; for 2.5 h;
Stage #2: with hydrogenchloride in water;N,N-dimethyl-formamide at 20; for 1 h;Inert atmosphere;

Steps:

A Step A. 1 -Chloro-2-(difluoromethoxy)-4-nitrobenzene.

A mixture of 2-chloro-5- nitrophenol (10 g, 58 mmol), K2C03 (9.4 g, 68 mmol), and sodium chlorodifluoroacetate (18 g, 115 mmol) in DMF (192 mL) and H20 (25 mL) was degassed with nitrogen for 5 minutes, and then the reaction mixture washeated to 100°C for2.5 h. The mixture was cooled tort and 12 N HCI (17 mL) and H20 (25 mL) was added. The mixture was stirred at room temperature for 1 h. The resulting mixture was then cooled to 0 °C, and an aqueous solution of 1 N NaOH (213 mL) was added portion wise. The reaction mixture was diluted with H20 and extracted with Et20 (2X). The organic layer was furtherwashed with H20 (lx), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification (FCC, Si02, 0-50% DCM in hexanes) afforded the title compound (12 g, 55 mmol, 95% yield). 1H NMR (400 MHz, CDCI3) ? 8.15-8.12 (m, 1H), 8.08 (dd, J= 8.8, 2.5 Hz, 1H), 7.65 (d, J= 8.8 Hz, 1H),6.65 (t, J = 71 .9 Hz, 1 H).

References:

WO2017/139428,2017,A1 Location in patent:Page/Page column 104; 105