Phosphorus tribromide → 5-(Bromomethyl)-1-methyl-3-nitro-1H-pyrazole

Temperature

0 °C

A 25-mL three-necked round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and reflux condenser was purged with nitrogen and charged with 19 (1.83 g, 11.2 mmol) and chloroform (10 mL). The reaction was cooled to 0° C. using an ice bath and phosphorous tribromide (3.02 g, 11.2 mmol) was added dropwise. The cooling bath was removed and the reaction stirred at reflux for 2 h. After this time, the reaction was cooled to 0° C. and diluted with methylene chloride (100 mL). Saturated aqueous sodium bicarbonate (25 mL) was added until a pH of 8.5 was reached. The layers were separated, and the aqueous layer was extracted with methylene chloride (3×20 mL). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford an 87% yield (1.66 g) of 20 as an off-white solid: mp 41-13° C.; 1H NMR (300 MHz, CDCl3) δ 6.91 (s, 1H), 4.44 (s, 2H), 4.01 (s, 3H).

1. customA 25-mL three-necked round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet
2. temperaturereflux condenser
3. customwas purged with nitrogen
4. customThe cooling bath was removed
5. temperatureat reflux for 2 h
6. temperatureAfter this time, the reaction was cooled to 0° C.
7. additiondiluted with methylene chloride (100 mL)
8. additionSaturated aqueous sodium bicarbonate (25 mL) was added until a pH of 8.5
9. customThe layers were separated
10. extractionthe aqueous layer was extracted with methylene chloride (3×20 mL)
11. washThe combined organic layers were washed with brine (30 mL)
12. dry with materialdried over sodium sulfate
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by column chromatography

ORD record

ord-8c85aeb2e0964f958bcef73b1810cbe1

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598174B2