1,1-Dichloroethane → 1-Cyclopropyl-4-nitro-1H-pyrazole

HRID 1772102Notes

Reaction equation

HRID 1772102 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].[CH:9]1(B(O)O)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Na+].[Na+].ClC(Cl)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:9]1([N:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:8]=[N:7]2)[CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 63651,1-DichloroethaneHCID 10340Sodium CarbonateHCID 163764-nitro-1H-pyrazoleHCID 2760897Cyclopropylboronic acid

Product 1

HCID 566043181-Cyclopropyl-4-nitro-1H-pyrazoleYield 37%

Reagents, catalysts & solvents 1

HCID 8895Cupric acetateCatalyst

Conditions

Temperature
70 °C

Procedure

A 100-mL three-neck round-bottomed flask equipped with a reflux condenser and magnetic stirrer was purged with nitrogen and charged with 4-nitropyrazole (500 mg, 4.42 mmol), cyclopropylboronic acid (760 mg, 8.84 mmol), sodium carbonate (937 mg, 8.84 mmol), 2,2′-bipryidyl (690 mg, 4.42 mmol), and dichloroethane (45 mL). After bubbling nitrogen through the resulting suspension for 30 min, copper (II) acetate (802 mg, 4.42 mmol) was added, and the reaction mixture was heated at 70° C. (oil bath temperature) for 6 h. After this time, the mixture was cooled to room temperature and filtered. The filtrate was diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×50 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% ethyl acetate/hexanes) to afford a 37% yield (185 mg) of 109a as an off-white solid: mp 44-45° C.; 1H NMR (500 MHz, CDCl3) δ 8.18 (s, 1H), 8.03 (s, 1H), 3.67 (s, 1H), 1.16 (m, 4H); MS (APCI+) m/z 154.1 (M+H).

Workup

  1. customA 100-mL three-neck round-bottomed flask equipped with a reflux condenser and magnetic stirrer
  2. customwas purged with nitrogen
  3. customAfter bubbling nitrogen through the resulting suspension for 30 min
  4. temperatureAfter this time, the mixture was cooled to room temperature
  5. filtrationfiltered
  6. additionThe filtrate was diluted with ethyl acetate (150 mL) and water (30 mL)
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography (silica, 0% to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-97024062086846b98f7279003d93e9be
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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