Sodium hydride → 1-Tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonate

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Reaction Conditions

Reaction Steps

tert-Butyl ethyl malonate (41.3 ml, 211 mmol) was added drop-wise to a suspension of sodium hydride (19.33 g, 483 mmol) in dioxane (1000 mL) at 0° C. The reaction was stirred at 0° C. for 1 hr and then allowed to warm to ambient temperature. 3,6-dichloropyridazine (30 g, 201 mmol) was then added portion wise at 25° C. The reaction was stirred at reflux for 2 hrs and then solvent was removed via rotary evaporation. The resulting residue was dissolved in EtOAc (400 mL), and the organic phase was washed with saturated NaHCO3 (400 mL), dried over MgSO4, filtered, and concentrated to dryness via rotary evaporation. This reaction was repeated. The combined crude residues from both batches was purified via MPLC (Hex:EtOAc, 8:2) to provide the title compound, 1-tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonate (86.5 g, 288 mmol, 71.3%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-1.23 (m, 3 H) 1.36-1.52 (m, 9 H) 4.20 (m, J=10.71, 7.22, 7.22, 3.85, 3.85 Hz, 2 H) 5.29 (s, 1 H) 7.85 (d, J=8.84 Hz, 1 H) 7.99 (d, J=8.84 Hz, 1 H). ESI-MS:m/z 301.2 (M+H)+.

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