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

Participants

Reaction Steps

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).

Provenance & Evidence