4-Methylpyrazole → tert-butyl 1-(4-methyl-1H-pyrazol-1-yl)cyclopropanecarboxylate

HRID 931062Notes

Reaction equation

HRID 931062 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.Br[CH:10]([CH2:18][CH2:19]Br)[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]>O1CCCC1>[CH3:3][C:4]1[CH:5]=[N:6][N:7]([C:10]2([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:19][CH2:18]2)[CH:8]=1

Participants

5

Reactant 3

HCID 34064-MethylpyrazoleHCID 24758Sodium hydrideHCID 5107723tert-Butyl 2,4-dibromobutyrate

Product 1

HCID 117966666tert-butyl 1-(4-methyl-1H-pyrazol-1-yl)cyclopropanecarboxylateYield 44.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 25 mL round bottom flask were added sodium hydride (60% dispersion in mineral oil, 164.3 mg, 4.1 mmol) and anhydrous tetrahydrofuran (8 mL). The mixture was cooled with an ice-water bath before a solution of 4-methylpyrazole (204.2 mg, 2.487 mmol) in anhydrous tetrahydrofuran (2 mL) was added. The mixture was stirred in the ice-water bath for 30 minutes before tert-butyl 2,4-dibromobutanoate (0.48 mL, 2.2 mmol) was added dropwise at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 18 h. The solvent was removed under reduced pressure and water and ethyl acetate were added to the residue. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via flash chromatography (0-50% ethyl acetate in heptanes) to afford tert-butyl 1-(4-methyl-1H-pyrazol-1-yl)cyclopropanecarboxylate (218 mg, 44%). 1H NMR (400 MHz, CDCl3) δ 1.33 (s, 9H), 1.45-1.51 (m, 2H), 1.61-1.67 (m, 2H)H), 1.98-2.01 (m, 3H)H), 7.21 (s, 1H), 7.23-7.26 (m, 1H).

Workup

  1. additionwas added
  2. additionwas added dropwise at 0° C
  3. waitat room temperature for 18 h
  4. customThe solvent was removed under reduced pressure and water and ethyl acetate
  5. additionwere added to the residue
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  8. dry with materialThe combined organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified via flash chromatography (0-50% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-4864464653694d15affa015d0656e42a
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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