Methyl 2-Methoxy-4-Methyl-5-nitrobenzoate synthesis

Yield:1057652-79-5 63%

Reaction Conditions:

with nitric acid;acetic acid in acetic anhydride at 0 - 40; for 12 h;

Steps:

2

To a mixture of methyl 2-methoxy-4-methylbenzoate (82 g, 0.46 mol) in acetic acid/acetic anhydride (1/1, 400 mL) was added nitric acid (128 mL) dropwise at 0 °C and then raised to 40 °C slowly and stirred for 12 h. The resulting mixture was poured into ice water and extracted with DCM. The organic phases were washed with brine, dried over Na₂S0₄ and concentrated under reduce pressure. The crude product was purified through silica gel flash column chromatography (cyclohexane /DCM/ethyl acetate = 8/2/1) to afford methyl 2-methoxy- 4-methyl-5-nitrobenzoate as an off-white solid (65 g, 63%). 1H NMR (400 MHz, CDCl₃): d 8.62 (s, 1H), 6.86 (s, 1H), 4.00 (s, 3H), 3.91 (s, 3H), 2.71 (s, 3H).

References:

WO2020/33782,2020,A1 Location in patent:Paragraph 0238