Dibromodifluoromethane → 4-Bromo-1-(bromodifluoromethyl)-1H-pyrazole

Temperature

0 °C

60% suspension of NaH in oil (19.2 g, 0.48 mol) was washed with hexane (3×150 mL), suspended in DMF (200 mL) and cooled to 0° C. under N2. Then, a solution of bromide 4 (61.7 g, 0.42 mol) in DMF (80 mL) was added dropwise over a period of 30 min while maintaining the temperature of the mixture below 0° C. (acetone-dry ice bath at −10° C.). The mixture was stirred at 0° C. for 5 min and a solution of CBr2F2 (47.4 mL, 0.515 mol) in DMF (60 mL) was added dropwise at <0° C. over a period of 30 min. Cooling bath was removed and the mixture was stirred for 2 h at RT. Reaction mixture was carefully poured into water (1 L) and extracted with ether (4×400 mL). Combined organic extracts were washed with water (3×200 mL), dried (MgSO4), and concentrated to afford crude 5 (125.68 g) as an orange liquid. A portion of this product (122.73 g) was distilled under reduced pressure to afford 5 (72.68 g, 64%) as colourless liquid b.p. 84-90° C./30 mm Hg. 1H NMR (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.88 (s, 1H). Some (about 9% mol) contaminants giving rise to signals at δ 7.60 and 7.68 were also present.

1. temperatureCooling bath
2. customwas removed
3. stirringthe mixture was stirred for 2 h at RT
4. customReaction mixture
5. extractionextracted with ether (4×400 mL)
6. washCombined organic extracts were washed with water (3×200 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated

ORD record

ord-8e6b198bb49c49c5a41a3b1e2f182d28

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08178552B2