Methyl iodide → Methyl 1-methyl-4-nitro-1H-pyrazole-3-carboxylate

Temperature

0 °C

A mixture of sodium hydride (167 mg, 6.96 mmol) in tetrahydrofuran (15 mL) cooled to 0° C. was treated with a solution of 4-nitro-1H-pyrazole-3-carboxylic acid methyl ester (1.0 g, 5.8 mmol) in tetrahydrofuran (10 mL). This mixture was stirred at 0° C. for 1 h. It was then treated with methyl iodide (0.54 mL, 8.7 mmol). The reaction was stirred at 25° C. for 18 h. At this time, the reaction was cooled to 0° C. and was then quenched with a saturated aqueous ammonium chloride solution and diluted with ethyl acetate (200 mL). This solution was washed with water (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was slurried in 40% ethyl acetate/petroleum ether and cooled in the freezer for 15 min. At this time, the solids were collected by filtration to afford 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid methyl ester (889 mg, 82.8%) as a white solid: 1H NMR (DMSO-d6, 300 MHz) δ8.93 (s, 1H), 3.92 (s, 3H), 3.86 (s, 3H).

1. stirringThe reaction was stirred at 25° C. for 18 h
2. temperatureAt this time, the reaction was cooled to 0° C.
3. customwas then quenched with a saturated aqueous ammonium chloride solution
4. additiondiluted with ethyl acetate (200 mL)
5. washThis solution was washed with water (1×100 mL)
6. dry with materialThe organics were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. temperaturecooled in the freezer for 15 min
10. filtrationAt this time, the solids were collected by filtration

ORD record

ord-561ebc643d1d406295fc3fe8450cc849

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07135475B2