Methyl iodide → Methyl 1-methyl-5-nitro-1H-pyrazole-3-carboxylate

HRID 541427Notes

Reaction equation

HRID 541427 reaction equation
[N+:1]([C:4]1[NH:8][N:7]=[C:6]([C:9]([O:11][CH3:12])=[O:10])[CH:5]=1)([O-:3])=[O:2].[C:13](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[CH3:13][N:8]1[C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]([C:9]([O:11][CH3:12])=[O:10])=[N:7]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 135452337methyl 3-nitro-1H-pyrazole-5-carboxylate

Product 1

HCID 50896836Methyl 1-methyl-5-nitro-1H-pyrazole-3-carboxylateYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

Into a round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of methyl 5-nitro-1H-pyrazole-3-carboxylate (3.00 g, 17.5 mmol, 1.00 equiv) in N,N-dimethylformamide (30 mL). Potassium carbonate (4.84 g, 35.0 mmol, 2.00 equiv) and CH3I (2.98 g, 21.0 mmol, 1.20 equiv) were added at 0° C. The resulting solution was stirred for 2 h at 40° C. in an oil bath. After cooling to ambient temperature, the solids were removed by filtration followed by the addition of 120 mL of ice water. The mixture was extracted with 3×100 mL of ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by re-crystallization from ether. This resulted in 1.10 g (34%) of methyl 1-methyl-3-nitro-1H-pyrazole-5-carboxylate as a white solid. m/z (ES+) 186 (M+H)+. 1H-NMR, (300 MHz, DMSO-d6, ppm): ˜7.57 (s, 1H), 4.22 (s, 3H), 3.91 (s, 3H). The filtrate was concentrated under vacuum and the crude product (2 g) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (10% CH3CN up to 56.5% in 10 min); Detector, uv 254 nm. The fractions containing pure compound were combined and concentrated to yield 470 mg (15%) of methyl 1-methyl-5-nitro-1H-pyrazole-3-carboxylate as a white solid. m/z (ES+) 186 (M+H)+. 1H-NMR, (300 MHz, DMSO-d6, ppm): □□ 7.64 (1H, s), 4.24 (3H, s), 3.87 (3H, s).

Workup

  1. customInto a round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureAfter cooling to ambient temperature
  4. customthe solids were removed by filtration
  5. additionfollowed by the addition of 120 mL of ice water
  6. extractionThe mixture was extracted with 3×100 mL of ethyl acetate
  7. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe crude product was purified by re-crystallization from ether
  10. customThis resulted in 1.10 g (34%) of methyl 1-methyl-3-nitro-1H-pyrazole-5-carboxylate as a white solid
  11. concentrationThe filtrate was concentrated under vacuum
  12. customthe crude product (2 g) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  13. waitmobile phase, water with 0.05% TFA and CH3CN (10% CH3CN up to 56.5% in 10 min)
  14. additionThe fractions containing pure compound
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-12ff4fcc08b74fb6b03cc1f46c5e045b
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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