1,4-Dioxane → HCID 58936501, compound

Participants

Reaction Conditions

Reaction Steps

A thick mixture of 6-tert-butoxy-2,5-difluoro-nicotinonitrile (18.22 g, 85.9 mmol), as prepared in Example 1b, malonic acid tert-butyl ester methyl ester sodium salt (34.49 g, 176 mmol), as prepared in the previous step, and dioxane (110 mL) was stirred under argon at 95° C. (oil bath) for 14 h. The resulting homogeneous dark amber solution was allowed to cool to rt, diluted with ether (150 mL), and washed with a solution of 1.0 M NaH2PO4 (200 mL) containing 2.0 M citric acid (40 mL). The aqueous layer was back-extracted with ether (1×100 mL), the organic layers were combined, washed with 4 M NaCl (1×100 mL), dried (Na2SO4), and concentrated under reduced pressure. Malonic acid tert-butyl ester methyl ester was largely removed from the residue by high vacuum at 95° C. for 1 h to afford the title compound as a clear, dark brown viscous oil (32.37 g, approx. 100% crude yield). 1H-NMR (300 MHz, CDCl3) δ 7.48 (d, 1H), 5.06 (s, 1H), 3.80 (s, 3H), 1.62 (s, 9H), 1.47 (s, 9H).

Provenance & Evidence