Chloroform → 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole

Temperature

-5 °C

A 500-mL three-necked round-bottomed, flask equipped with a magnetic stirrer, nitrogen inlet and reflux condenser was purged with nitrogen and charged with (1-(2-bromoethyl)-3-nitro-1H-pyrazol-5-yl)methanol (37.0 g, 148 mmol) and chloroform (160 mL). The reaction was cooled to −5° C. using an ice/acetone bath and phosphorous tribromide (40.0 g, 148 mmol) was added portionwise. The cooling bath was removed and the reaction stirred at reflux for 2 h. After this time, the reaction was cooled to −5° C. and saturated aqueous sodium bicarbonate (250 mL) was added until a pH of 8.5 was reached. The mixture was extracted with ethyl acetate (3×150 mL) and the combined organic layers were washed with saturated aqueous sodium carbonate (2×50 mL), brine (75 mL), dried over sodium sulfate and the drying agent was removed by filtration. The filtrate was concentrated under reduced pressure to afford a yellow residue that was dissolved with gentle heating in methylene chloride (60 mL). Hexanes (approximately 20 mL) was added and the solution became cloudy. The mixture was heated until a solid precipitate formed, methylene chloride (9 mL) was added and the solution became clear. The solution was left to cool to room temperature and after 4 h the resulting crystals were collected by vacuum filtration. The filter cake was washed with a ice cold 1:2 mixture of methylene chloride:hexanes (2×20 mL) to afford 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole (19.7 g). The combined filtrates were evaporated and the procedure was performed again to afford an additional 9.70 g of 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole. The solids were combined and dried under high vacuum for 18 h to afford a 57% yield (26.0 g) of 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole as white crystals: mp 95-97° C.; 1H NMR (300 MHz, CDCl3) δ 6.93 (s, 1H), 4.63 (t, 2H, J=6.0 Hz), 4.54 (s, 214), 3.86 (t, 2H, J=6.0 HZ).

1. customA 500-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 −5° C.
7. additionsaturated aqueous sodium bicarbonate (250 mL) was added until a pH of 8.5
8. extractionThe mixture was extracted with ethyl acetate (3×150 mL)
9. washthe combined organic layers were washed with saturated aqueous sodium carbonate (2×50 mL), brine (75 mL)
10. dry with materialdried over sodium sulfate
11. customthe drying agent was removed by filtration
12. concentrationThe filtrate was concentrated under reduced pressure
13. customto afford a yellow residue that
14. dissolutionwas dissolved
15. temperatureThe mixture was heated until a solid precipitate
16. customformed
17. waitThe solution was left
18. temperatureto cool to room temperature and after 4 h the resulting crystals
19. filtrationwere collected by vacuum filtration
20. washThe filter cake was washed with a ice cold 1:2 mixture of methylene chloride

ORD record

ord-33552e0933824bce9fc9f9d0b8b06378

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598174B2