Yield:878572-17-9 68.52%

Reaction Conditions:

with sulfuric acid;nitric acid at 0 - 75; for 5 h;

Steps:

533.1 Step 1.

To a mixture of 4-fluoro-3-(trifluoromethyl)benzoic acid (3 g, 14.42 mmol) in HNO₃ (25 mL) was added H₂SO₄ (6.90 g, 70.35 mmol, 3.75 mL) at 0°C. The mixture was stirred at 75°C for 5 h. The reaction mixture was quenched with ice water (40 mL) and extracted with EtOAc. The combined organic layers was dried over Na₂SO₄, filtered and concentrated under reduced pressure to give 4-fluoro-3-nitro-5-(trifluoromethyl)benzoic acid (2.5 g, 68.52% yield). ¹H NMR (400MHz, DMSO-d₆) d = 8.78 (dd, J = 4.5, 1H), 8.47 (dd, J = 3.25, 1H).

References:

WO2020/180770,2020,A1 Location in patent:Paragraph 00738