2-Bromo-3-fluoro-6-nitroaniline 97% synthesis

Yield: 97%

Reaction Conditions:

with ammonium carbonate;triethylamine in N,N-dimethyl-formamide at 20; for 48 h;

Steps:

2 Step 2: 2-bromo-3-fluoro-6-nitroaniline
Prepared according to WO 2010/046388. 2-Bromo-l ,3-difluoro-4-nitrobenzene (27.15 g, 114 mmol) was treated with ammonium carbonate (Sigma Aldrich, 10.96 g, 1 14 mmol) and DMF (200 mL) followed by Et₃N (47.7 mL, 342 mmol) and stirred at RT for 48 h. The mixture was treated with water and extracted with DCM (300 mL). The DCM layer was washed with water (3 x 200 mL) and brine (3 x 200 mL), dried over MgS0₄, filtered and concentrated affording crude 2-bromo-3-fluoro-6-nitroaniline (25.99 g, 11 1 mmol, 97 % yield) as a bright yellow amorphous solid: ^{FontWeight="Bold" FontSize="10"} H NMR (400 MHz, CDCl₃) δ ppm 8.22 (1 H, dd, J=9.6, 5.9 Hz), 6.81 (2 H, br. s.), 6.56 (2 H, dd, J=9.6, 7.2 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ ppm -90.92 (1 F, s). m/z (ESI, +ve ion) 234.9/236.9 (M+H)⁺.

References:

AMGEN INC.;CEE, Victor J.;BROWN, James;CHAVEZ JR., Frank;CHEN, Jian J.;HERBERICH, Bradley J.;HARRINGTON, Essa Hu;LANMAN, Brian Alan;LEE, Matthew;PETTUS, Liping H.;REED, Anthony B.;TASKER, Andrew;WANG, Hui-Ling;WU, Bin;WURZ, Ryan WO2014/22752, 2014, A1 Location in patent:Page/Page column 81