Sodium hydride → 1-(4-methoxybenzyl)-1H-pyrazole-5-carbaldehyde

HRID 1865559Notes

Reaction equation

HRID 1865559 reaction equation
[CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[CH:12]=[CH:11][C:10](C=O)=[N:9]2)=[CH:5][CH:4]=1.[H-].[Na+].N1C=CC([CH:24]=[O:25])=N1.COC1C=CC(CCl)=CC=1>CN(C=O)C.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]([CH:24]=[O:25])=[CH:11][CH:10]=[N:9]2)=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 122183831H-Pyrazole-3-carbaldehydeHCID 86621225HCID 86621225, compound

Product 1

HCID 103309201-(4-methoxybenzyl)-1H-pyrazole-5-carbaldehydeYield 12.26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

1-(4-methoxy-benzyl)-1H-pyrazole-3-carbaldehyde: Sodium hydride, 60% in oil (0.229 g, 5.72 mmol), was suspended in DMF (5 mL) at 0° C. under nitrogen with stirring. A solution of 1H-pyrazole-3-carbaldehyde (0.5 g, 5.20 mmol) in DMF (5 mL) was added over 5-10 minutes via syringe. The resulting mixture was stirred at 0-5° C. for 10-15 min followed by addition of 4-methoxybenzyl chloride (0.815 mL, 5.98 mmol). Stirring was continued overnight allowing ice bath to melt and the reaction to assume rt. The reaction mixture was diluted with water and extracted 3× with EtOAc. The combined extracts were washed with water and brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The residue was dissolved in methylene chloride and charged to a 120 g silica gel cartridge which was eluted with a 30 min gradient from 0-40% EtOAc in hexane. The major product was 1-(4-methoxybenzyl)-1H-pyrazole-3-carbaldehyde (0.768 g, 68.3%) which was obtained as a colorless oil. 1HNMR (500 MHz, CDCl3) δ: 9.99 (1H, s), 7.38 (1H, s), 7.22 (2H, d, J=8.2 Hz), 6.90 (2H, d, J=8.8 Hz), 6.80 (1H, d, J=2.7 Hz), 5.32 (2H, s), 3.81 (3H, s). Evaporation of the fractions from the minor peak yielded 1-(4-methoxybenzyl)-1H-pyrazole-5-carbaldehyde as a crystalline solid (0.138 g, 12.26%). 1HNMR (500 MHz, CDCl3) δ: 9.85 (1H, s), 7.59 (1H, d, J=2.2 Hz), 7.26 (2H, d, J=8.8 Hz), 6.91 (1H, d, J=2.2 Hz), 6.83 (2H, d, J=8.8 Hz), 5.67 (2H, s), 3.77 (3H, s).

Workup

  1. stirringThe resulting mixture was stirred at 0-5° C. for 10-15 min
  2. stirringStirring
  3. customthe reaction
  4. customto assume rt
  5. extractionextracted 3× with EtOAc
  6. washThe combined extracts were washed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe residue was dissolved in methylene chloride
  11. additioncharged to a 120 g silica gel cartridge which
  12. washwas eluted with a 30 min gradient from 0-40% EtOAc in hexane
  13. customwas obtained as a colorless oil
  14. customEvaporation of the fractions from the minor peak

Sources & evidence

ORD record
ord-310a908461a24ce49995b6eee9829611
Source dataset
uspto-grants-2009_12
Patent number
US07626039B2

Reaction notes

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