Methanol → HCID 90092735, compound

Participants

Reaction Steps

Under nitrogen atmosphere, to a solution of 4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(pyridin-2-yl)-1H-pyrazole-5-carbaldehyde (9f) (137 mg, 0.43 mmol) in anhydrous dichloromethane (2 mL) at 0° C. were successively added zinc iodide (14 mg, 0.04 mmol) and trimethylsilyl cyanide (64 μL, 0.51 mmol). The mixture was stirred at room temperature for 4 hours and then heated at 50° C. for 3 days. After cooling to room temperature, a 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 (0.36 mL, 5.13 mmol) in anhydrous methanol (2 mL), previously stirred 20 minutes at 0° C. under nitrogen atmosphere. The mixture was stirred at room temperature overnight. The solution was concentrated in vacuo and 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 (dichloromethane/7M ammonia in methanol 97/3) to provide methyl 2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl]-2-hydroxyacetate (9g) (64 mg, 0.17 mmol, 39%).

Provenance & Evidence