Nitric Acid → 1-Methoxy-2-methyl-4-nitrobenzene

2-Methylanisole (2.5 ml) in acetic acid (140 ml) and dichloromethane (150 ml) was cooled to 15° C. Concentrated nitric acid (20 ml) was added slowly keeping the temperature of the reaction below 40° C. The reaction was stirred at ambient temperature for 30 minutes and cooled to 0° C. before adding fuming nitric acid (50 ml) dropwise. The reaction mixture was allowed to warm to ambient temperature slowly and stirred for a further 4 days. The reaction mixture was poured onto ice water (600 ml) and the organic layer was washed with water (2×40 ml) and saturated sodium hydrogencarbonate (2×40 ml), dried over magnesium sulfate and concentrated. The residual deep red solid was subjected to flash silica chromatography on silica eluting with isohexane/ethyl acetate (9:1) to (7:3) to yield 1-methoxy-2-methyl-4-nitrobenzene (2.70 g) as an off white solid. LC-MS (Method J): RT 3.74 minutes, 168.27 (M+H)+.

1. customthe temperature of the reaction below 40° C
2. temperaturecooled to 0° C.
3. temperatureto warm to ambient temperature slowly
4. stirringstirred for a further 4 days
5. additionThe reaction mixture was poured onto ice water (600 ml)
6. washthe organic layer was washed with water (2×40 ml) and saturated sodium hydrogencarbonate (2×40 ml)
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated

ORD record

ord-457368242e9642d3a3116539a99be8f2

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288425B2