Iodoethane → 1-Ethyl-4-nitro-1H-pyrazole

Temperature

0 °C

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen inlet and charged with 4-nitropyrazole (3.00 g, 26.5 mmol) and DMF (50 mL). The mixture was cooled to 0° C. using an ice bath. Sodium hydride (60% dispersion in mineral oil, 1.17 g, 29.2 mmol) was added portionwise. After the addition was complete, the mixture was stirred at 0° C. for 30 min. After that time, iodoethane (6.21 g, 39.8 mmol) was added over 15 min. After the addition was complete, the mixture was stirred at 0° C. for 30 min and then at room temperature for 3 h. After this time, the mixture was concentrated in vacuo. The residue was diluted with water (200 mL). The resulting precipitate was filtered, and the filter cake was dried in the oven to afford a 51% (1.90 g) of 111a as an off-white solid. The aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 50% hexanes/ethyl acetate) to afford another 49% yield (1.84 g, in total quantitative yield (3.74 g)) of 111a as an off-white solid: mp 54-55° C.; 1H NMR (300 MHz, CDCl3) δ 8.14 (s, 1H), 8.07 (s, 1H), 4.22 (q, 2H, J=7.2 Hz), 3.41 (s, 3H), 1.56 (s, 3H, J=7.2 Hz); MS (ESI+) m/z 142.0 (M+H).

1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer
2. customwas purged with nitrogen inlet
3. additionAfter the addition
4. additionAfter the addition
5. stirringthe mixture was stirred at 0° C. for 30 min
6. waitat room temperature for 3 h
7. concentrationAfter this time, the mixture was concentrated in vacuo
8. additionThe residue was diluted with water (200 mL)
9. filtrationThe resulting precipitate was filtered
10. customthe filter cake was dried in the oven

ORD record

ord-f900a2f0e10449baa67daf8548b8aa80

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249123B2