Hexachloroethane → 5-chloro-1-methyl-4-nitro-1H-pyrazole

Temperature

-78 °C

Following WO 2007/99326, to a 500 mL 3-neck-round bottom flask was added 1-methyl-4-nitro-1H-pyrazole (4.30 g, 33.8 mmol) and THF (12 mL). The mixture was cooled to −78° C. and lithium hexamethyldisilazide in THF (1M, 88.4 mL, 90 mmol) was added dropwise via an addition funnel over 20 min. The brown mixture was stirred for 30 min and warmed to −45° C. over 30 min. The mixture was cooled back down to −78° C. and hexachloroethane (10.5 g, 44.2 mmol) dissolved in THF (20 mL) was added via an addition funnel over 15 min. The mixture was stirred for 2.5 h, warmed from −78° C. to −40° C. and the reaction was monitored by LCMS. Upon completion of the reaction, the reaction was quenched with a solution of saturated NH4Cl (150 mL), and ethyl acetate (100 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layer was washed with water (150 mL), dried over Na2SO4 and the organic solvent was distilled off. The crude product was purified via flash chromatography (CH2Cl2/7% MeOH) to yield 5-chloro-1-methyl-4-nitro-1H-pyrazole as a white solid (1.40 g, 20%). 1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 3.92 (s, 3H); ESIMS m/z=162.0 (M+1)

1. temperaturewarmed to −45° C. over 30 min
2. additionwas added via an addition funnel over 15 min
3. stirringThe mixture was stirred for 2.5 h
4. temperaturewarmed from −78° C. to −40° C.
5. customUpon completion of the reaction
6. customthe reaction was quenched with a solution of saturated NH4Cl (150 mL), and ethyl acetate (100 mL)
7. additionwas added
8. customThe organic layer was separated
9. extractionthe aqueous layer was extracted with ethyl acetate (100 mL)
10. washThe combined organic layer was washed with water (150 mL)
11. dry with materialdried over Na2SO4
12. distillationthe organic solvent was distilled off
13. customThe crude product was purified via flash chromatography (CH2Cl2/7% MeOH)

ORD record

ord-fd304754f8384c6ca201ceebc27aaa68

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328106B2