Pyridine, hydrofluoride (1:1) → Ethyl 5-methyl 2-fluoro-6-methyl-4-(p-tolyl)pyridine-3,5-dicarboxylate

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Reaction Conditions

Reaction Steps

3-Ethyl 5-methyl 2-amino-6-methyl-4-(p-tolyl)pyridine-3,5-dicarboxylate (5.0 g, 15.23 mmol) (Example 1, Step C) was dissolved in tetrahydrofuran (50 mL) and cooled to 0° C. Sodium nitrite (5.25 g, 76.15 mmol) was added followed by HF-Pyridine (4.0 mL, 160 mmol). The reaction was stirred at ambient temperature until complete by LCMS. Ethyl acetate and sodium bicarbonate solution was added, the precipitated solid was filtered, and the filtrate was extracted with ethyl acetate, dried over sodium sulfate, and purified by silica-gel chromatography (0-30% hexanes/ethyl acetate) to afford the title compound as a colorless oil (2.91 g, 58%): 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.18-7.24 (m, 2 H) 7.12-7.18 (m, 2 H) 4.11 (q, J=7.22 Hz, 2 H) 3.55-3.60 (m, 3 H) 2.55-2.59 (m, 3 H) 2.39 (s, 3 H) 1.03 (t, J=7.12 Hz, 3 H); LCMS (m/z) ES+=332 (M+1).

Provenance & Evidence