Methanol → HCID 90092585, compound

Participants

Reaction Steps

Under nitrogen atmosphere, to a solution of 1-methyl-4-(5-methyl-3,4-dihydro-2H-1-benzopyran-6-yl)-3-(thiophen-2-yl)-1H-pyrazole-5-carbaldehyde (7h) (103 mg, 0.30 mmol) in anhydrous dichloromethane (2 mL) at 0° C. were successively added zinc iodide (10 mg, 0.03 mmol) and trimethylsilyl cyanide (46 μL, 0.37 mmol). The mixture was stirred at room temperature for 88 hours then heated at 40° C. for 4 hours. 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 (1 mL), was added to a solution of acetyl chloride (0.26 mL, 3.65 mmol) in anhydrous methanol (2 mL), previously stirred for 20 minutes at 0° C. under nitrogen atmosphere. The mixture was 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 (dichloromethane/ethyl acetate 80/20) to provide methyl 2-hydroxy-2-[1-methyl-4-(5-methyl-3,4-dihydro-2H-1-benzopyran-6-yl)-3-(thiophen-2-yl)-1H-pyrazol-5-yl]acetate (7i) (79 mg, 0.20 mmol, 65%).

Provenance & Evidence