Yield: 100%

Reaction Conditions:

with sulfuric acid;nitric acid at 0; for 3 h;

Steps:

Intermediate G: 2-Fluoro-4-methyl-5-nitrobenzoic acid
In a 250 mL round-bottomed flask was dissolved 2-fluoro-4-methylbenzoicacid (4 g, 26.0 mmol) in concentrated sulfuric acid (40 mL) at 0°C (completelydissolved). A mixture of 12 N H2504 (1.69 mL, 31.1 mmol) and 70% nitric acid(2.485 mL, 38.9 mmol) was added dropwise. After stirring for 3 h at 0 °C, an excessof ice water was added. The resulting solid was collected by vacuum filtration anddried to obtain the desired product (5.20 g, 100%) as a white solid. LCMS (ESI) m/e 200.4 [(M+H), calcd C8H7FNO4, 200.041; LC/MS retention time (method A): tR =0.72 mm.

References:

BRISTOL-MYERS SQUIBB COMPANY;LUO, Guanglin;CHEN, Ling WO2017/184658, 2017, A1 Location in patent:Page/Page column 66; 67