Yield:331765-71-0 91%

Reaction Conditions:

Stage #1: 3,5-difluorobenzoic acidwith sulfuric acid at 20; for 1 h;
Stage #2: with nitric acid at 20 - 45;

Steps:

Step 1 : 3,5-difluorobenzoic acid (80 g, 506 mmol) and sulfuric acid ( 250 ml) were stirred at room temperature for one hour. Then nitric acid (90 ml) was added, keeping the internal temperature below 45C with a water bath. The mixture was left at room temperature overnight. The reaction was poured slowly into ice and the resulting solid was filtered and washed with cold water to give compound 273 as a white solid (93.0 g, 91 % yield). This material was taken into the next step without further purification. ¹H NMR (400 MHz, DMSO-d6) δ 8.01 (ddd, J=10.9, 8.5, 2.8 Hz, 1 H), 7.71 ( dt, J= 8.4, 2.2 Hz, 1 H).

References:

WO2013/132376,2013,A1 Location in patent:Page/Page column 234