Methanol → HCID 90092984, compound

Participants

Reaction Steps

Under nitrogen atmosphere, to a solution of 4-(4,4-dimethylcyclohex-1-en-1-yl)-1-methyl-3-phenyl-1H-pyrazole-5-carbaldehyde (1d) (135 mg, 0.46 mmol) in anhydrous dichloromethane (2 mL) at 0° C. were successively added zinc iodide (15 mg, 0.05 mmol) and trimethylsilyl cyanide (69 μL, 0.55 mmol). The mixture was stirred at room temperature for 24 hours. An aqueous saturated solution of sodium hydrogenocarbonate (5 mL) was added. Layers were separated and the aqueous layer was extracted with dichloromethane (2×6 mL). The organic layers were dried over sodium sulfate and concentrated in vacuo. The residue, dissolved in anhydrous methanol (3 mL) was added to a solution of acetyl chloride (0.39 mL, 5.50 mmol) in anhydrous methanol (2 mL), previously stirred for 20 minutes at 0° C. under nitrogen atmosphere. The mixture was heated at 65° C. for 5 hours and stirred at room temperature overnight. The solution was concentrated in vacuo and a saturated solution of sodium hydrogenocarbonate (5 mL) was added to the residue. The aqueous layer was extracted with ethyl acetate (2×6 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (cyclohexane/ethyl acetate 70/30) to provide methyl 2-[4-(4,4-dimethylcyclohex-1-en-1-yl)-1-methyl-3-phenyl-1H-pyrazol-5-yl]-2-hydroxyacetate (1e) (135 mg, 0.38 mmol, 83%).

Provenance & Evidence