Methyl iodide → Acetic acid 2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of acetic acid 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester (34) (531 mg, 1.38 mmol), potassium carbonate (280 mg, 2.03 mmol) and methyl iodide (2 mL, 32.1 mmol) was warmed to 40° C. for 2 h. Additional methyl iodide was added (1 mL, 16.05 mmol) followed by potassium carbonate (140 mg, 1.01 mmol). The mixture was heated at 40° C. for 2 h and then was stirred at room temperature for 24 h. The reaction mixture was concentrated and the resulting residue was partitioned between ethyl acetate (50 mL) and water (25 mL). The water layer was re-extracted with ethyl acetate (25 mL). The organic layers were combined, dried with sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in 25% ethyl acetate in hexanes and was purified by flash chromatography (Biotage 40S) using silica gel eluted with 25-50% ethyl acetate in hexanes. The desired fractions were collected and concentrated under vacuum. The resulting solid was dried under high vacuum to afford 2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester (35) (395 mg, 72%) as a clear oil; LRMS for C18H20Cl2N2O4 (M+) m/z=399. Molecular Weight=399.2771; Exact Mass=398.0800

Provenance & Evidence